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250 Cards in this Set

  • Front
  • Back

Structure/Function:

This disorder affects the enzyme lysyl hydroxylase, results in a defect in collagen synthesis

Ehlers-Danlos syndrome

[A heterogenous group of disorders of collagen synthesis, marked by hyperextensible joints and skin; inheritance can be autosomal recessive or autosomal dominant, and at least one type is X-linked recessive]
Structure/Function:

Caused by mutations in the FBN1 gene, leading to the presence of mutant fibrillin protein in connective tissues
Marfan syndrome

[Inherited as an autosomal dominant syndrome; many patients have cardiovascular defects, including mitral valve prolapse and cystic medial necrosis, leading to aortic incompetence and dissecting aortic aneurysms]
Structure/Function:

A group of disorders involving the α₁ and α₂ chains of collagen usually inherited as an autosomal dominant trait
Osteogenesis imperfecta

[Sometimes called brittle-bone disease. Younger patients present with multiple childhood fractures (arousing suspicion of child abuse), and distinctive blue sclera]
Structure/Function:

This autosomal dominant condition is most often a result of mutations in the β-myosin heavy gene chain, important in generating contractions within the cardiac myocytes
Familial hypertrophic cardiomyopathy

[This disorder results in a disarray of the contraction apparatus within cardiac muscle cells, with the development of a thickened muscular wall; it can lead to sudden death due to arrhythmias in athletes]
Structure/Function:

Most cases are inherited as X-linked dominant mutations in the α₅ chain of collagen type IV, which is expessed in the affected tissues
Alport syndrome

[This syndrome is characterized by nephritis, nerve deafness, and cataracts]
Structure/Function:

This disorder results from a frame-shift mutation leading to the complete absence of a cytoskeletal protein important in maintaining the shape of the contracting myocyte
Duchenne muscular dystrophy (DMD)

[This debilitating disorder leads to clumsiness, followed by weakness of the girdle muscles; confinement to a wheelchair occurs by the teens and death due to respiratory failure by the early 20s]
Structure/Function:

This disorder results from a quantitative deficiency of the cytoskeletal protein dystrophin
Becker muscular dystrophy (BMD)

[This disorder is much less severe than Duchenne muscular dystrophy, with a later inset and nearly normal life span]
Structure/Function:

Deficiency of the cytoskeletal protein spectrin, resulting in cells that are less deformable and more vulnerable to destruction in the spleen
Hereditary spherocytosis

[This autosomal disorder is the most common inherited cause of hemolytic anemia in whites and results in spherical RBCs]
Structure/Function:

This autosomal recessive condition results from a defect in microtuble polymerization, with defects in neutrophil chemotaxis and phagolysosome formation
Chediak-Higashi syndrome

[Defects in the formation of functional phagolysosomes from the union of lysosomes with phagosomes (containing opsonized pyogenic bacteria) results in recurrent infections by such organisms]
Structure/Function:

This family of transcription factors contains the supersecondary structural helix-turn-helix motif and is important in pattern formation during embryonic development
Homeobox Proteins

[Also known as Hox genes, these transcription factors mediate DNA transcription by binding to DNA via helix-turn-helix motifs. Disruption of such interactions during development by synthetic retinoids results in congenital malformation.]
Structure/Function:

This disorder results from an alteration in the normal α-helical arrangement of a neuronal protein, with conversion to a pathogenic β-pleated sheet conformation after exposure to an infectious agent
Creutzfeld Jakob disease

[It is believed that the conformation of the endogenous protein is altered by a proteinaceous infectious agent known as a prion. Accumulation of the pathogenic form results in death of the affected neurons and the development of involuntary movements and increasing dementia.]
Structure/Function:

This genetic disease is caused by the deletion of a phenylalanin residue at the 508th amino acid (Δ508) of the transmembrane chloride ion channel
Cystic fibrosis

[One of the most common genetic diseases among whites, CF is due to mutations in the cystic fibrosis transmembrane regulator (CFTR); it produces viscous mucous secretions and recurrent, potentially fatal pulmonary infections]
Structure/Function:

These intracellular proteins act as molecular chaperones, aiding in the proper folding of newly translated proteins
Heat-Shock Proteins

[Mutations in these proteins are found in some cases of Charcot-Marie-Tooth disease (CMT), one of the most common heritable neuromuscular disorders]
Structure/Function:

Mutations in this important anti-protease lead to misfolded protein within the cell, resulting in a quantitative deficiency in the circulating protein, which is important in the remodeling of lung tissue
Alpha antitrypsin (AAT) deficiency

[Patients with AAT deficiency present with panacinar emphysema of the lungs due to unchecked protease activity in the lung. They also develop cirrhosis of the liver.]
Structure/Function:

This substance, produced by the C cells of the thyroid, accumulates to form the β-pleated sheets known as amyloid in medullary carcinoma of the thyroid
Calcitonin

[This hormone, involved in calcium metabolism, is overproduced in medullary carcinoma of the thyroid. In at-risk populations, serum levels of calcitonin are used to screen for this type of cancer.]
Structure/Function:

This substance contributes to the insoluble β-fibrils, or amyloid, that accumulates in the B-cell malignancy multiple myeloma
Immunoglobulin light chains

[Immunoglobulin light chains produced in excess in multiple myeloma form the amyloid that accumulates in the kidney and heart, contributing to renal failure (myeloma kidney) and cardiomyopathy, both of which complicate the disease]
Structure/Function:

This disorder results from defects in the ability to add glucosylphophatidylinositol (GPI) anchors posttranslationally to proteins destined to be covalently attached to the extracellular face of cell membranes
Paroxysmal nocturnal hemoglobinuria (PNH)

[The major consequence of this disorder is the inability to produce GPI-anchored complement regulatory proteins on the surface of red blood cells. As a consequence, patients develop bouts of hemolytic anemia with hemoglobinuria.]
Structure/Function:

This macromolecular complex is responsible for degrading proteins tagged for destruction by the addition of multiple ubiquitin molecules
Proteosome

[The agent bortezomib (Velcade) inhibits this complex and is used for the treatment of multiple myeloma]
Structure/Function:

This type of enzyme inhibitor binds to the active site of the enzyme, increasing the apparent Km without changing the Vmax
Competitive inhibitor

[Physostigmine is a competitive inhibitor of acetylcholinesterase. It is used to potentiate the activity of acetylcholine in the treatment of glaucoma and is also used to treat myastenia gravis.]
Structure/Function:

This type of enzyme inhibitor does not bind to the active site of the enzyme and therefore does not change the Km of the reaction; however, it does decrease the Vmax
Noncompetitive inhibitor

{EDTA is a commonly used noncompetitive inhibitor during the collection of blood samples from patients. It chelates the calcium required for the activation of serum proteases and proteins of the coagulation pathway.]
Structure/Function:

These enzyme inhibitors bind irreversibly to the enzyme active site; therefore the inhibition increases with the length of exposure to the substance
Irreversible inhibitors (suicide inhibitors)

[The nerve gas tabun and sarin are irreversible inhibitors of acetylcholinesterase. They cause symptoms due to increased acetylcholine, namely blurred vision, sweating, diarrhea, chest tightness, rapid breathing, and mental status changes.]
Carbohydrate Metabolism:

Defects in this enzyme of the hexose monophosphate shunt result in hemolytic anemia on exposure to oxidative agents
Glucose-6-phosphate dehydrogenase (G6PDH)

[The hexose monophosphate shunt pathway generates NADPH-reducing equivalents, necessary to regenerate glutathione, which protects against oxidative damage to hemoglobin]
Carbohydrate Metabolism:

A condition due to deficiency of α-L-iduronidase, a lysosomal enzyme, with the accumulation of the mucopolysaccharides heparin sulfate and dermatan sulfate
Hurler syndrome

[Accumulation of mucopolysaccharides in the heart, brain, liver, and other organs results in hepatomegaly, dwarfism, gargoyle-like facies, corneal clouding, mental retardation, and death by age 10]
Carbohydrate Metabolism:

A condition due to X-linked deficiency of the lysosomal enzyme L-iduronosulfate sulfatase, with accumulation of heparin sulfate and dermatan sulfate
Hunter syndrome

[Results in hepatomegaly, mild mental retardation, and no cataracts; demonstrates less severe symptomatology than Hurler syndrome]
Carbohydrate Metabolism:

A benign condition due to a genetic deficiency of fructokinase, which may be found incidentally due to an elevated "glucose" concentration in the urine on dipstick testing
Essential fructosuria

[Results in the accumulation of fructose in blood and urine, which, like glucose, is a reducing sugar that will give a falsely elevated "glucose" concentration on dipstick screening]
Carbohydrate Metabolism:

Deficiency of this glycolytic enzyme leads to the second most common enzyme-deficiency hemolytic anemia
Pyruvate kinase

[Deficiency results in inadequate production of ATP, which is needed by sodium channels to maintain osmotic equilibrium; the result is membrane lysis]
Carbohydrate Metabolism:

Rarely congenital, this acquired disaccharidase deficiency results in gas, bloating, and watery diarrhea upon consumption of dairy products
Lactase deficiency

[Inability to break down lactose to glucose and galactose leads to osmotic diarrhea as well as increased fermentation by intestinal flora]
Carbohydrate Metabolism:

This disorder results from a genetic deficiency of galactose-1-phosphate uridyltransferase, with accumulation of galactose-1-phosphate in tissues
Classic galactosemia

[Results in failure to thrive, infantile cataracts, mental retardation, and cirrhosis, with liver failure and death; can be prevented by excluding galactose from the diet early in life]
Carbohydrate Metabolism:

This disorder represents the less severe albeit less common form of galactosemia
Galactokinase-deficient galactosemia

[A defect in the first enzyme in the catabolism of galactose results in infantile cataracts]
Carbohydrate Metabolism:

This lysosomal storage disease results from a deficiency in the enzyme that adds a mannose-6-phosphate moiety, which is required to target proteins to the lysosome
I-cell disease

[Proteins destined to be targeted through the endoplasmic reticulum require the presence of a mannose-6-phosphate tag, they are released via the default secretory pathway to the outside of the cell. Release of such hydrolytic enzymes results in the buildup of partially degraded materials in intracellular inclusions.]
Carbohydrate Metabolism:

This disorder results from a genetic deficiency of muscle phosphorylase, with accumulation of glycogen in skeletal muscles.
McArdle disease

[Following exercise, results in painful muscle cramps and weakness due to rhabdomyolysis. Patients may experience bouts of myoglobinuria, which can lead to renal failure.]
Carbohydrate Metabolism:

This disorder results from a deficiency of the glycogen debranching enzyme amylo-1,6-glucosidase.
Cori disease

[This leads to the accumulation of glycogen in the liver, heart, and skeletal muscle which manifests as stunted growth, hepatomegaly, and hypoglycemia]
Carbohydrate Metabolism:

This disorder results from a defect in the lysosomal enzyme α-1,4-glucosidase, leading to the accumulation of glycogen within the organelle.
Pompe disease

[Results in the accumulation of glycogen in the liver, heart, and skeletal muscle; death by age 3 is usually due to cardiomegaly and heart failure]
Carbohydrate Metabolism:

This disorder results from the autosomal recessive deficiency of glucose-6-phosphate dehydrogenase.
Von Gierke disease

[Results in the accumulation of glycogen in the liver and kidney and presents with hepatomegaly and hypoglycemia]
Carbohydrate Metabolism:

Can result from the autosomal dominant deficiency of the glycolytic enzyme glucokinase; results in severe β-cell defects in insulin secretion.
Maturity-onset diabetes of the young (MODY)

[Other autosomal dominant deficiencies resulting in MODY include mutations in hepatocyte nuclear transcription factor (HNF-1α and HNF-4α)]
Carbohydrate Metabolism:

This genetic deficiency of a glycolytic enzyme leads to the accumulation of fructose-1-phosphate and inhibition of glucose production.
Aldolase deficiency

[Deficiency results in fructose intolerance and life-threatening hypoglycemia upon fructose consumption]
Carbohydrate Metabolism:

This mucopolysaccharidosis is due to a deficiency of β-glucuronidase, with accumulation of heparan sulfate, dermatan sulfate, and chondroitin 4,6 sulfate.
MPS Type VII or Sly syndrome

[Patients present with hepatomegaly, skeletal deformity, and developmental delay. Although experimental, much work has been accomplished in preparing the way for treatment of this disorder with gene therapy]
Carbohydrate Metabolism:

This form of mucopolysaccharidosis results from an accumulation of heparan sulfate secondary to a genetic deficiency of heparan sulfamidase, N-acetylglucosaminidase, or N-acetylglucosamine 6-sulfatase.
MPS Type III or Sanfilippo syndrome

[All three forms of Sanfilippo syndrome (A,B, and C), result from the corresponding enzyme deficiencies; they result in the developmental delay, loss of motor skills, and death by the second decade of life]
Carbohydrate Metabolism:

This disorder results from a genetic deficiency of galactose-6-sulfatase, leading to the accumulation of keratin sulfate and chondroitin 6-sulfate.
MPS Type IV or Morquio syndrome

[Unlike other mucopolysaccharidoses, Morquio syndrome is not associated with CNS involvement. The main features of the disease are severe skeletal dysplasia and short stature. Motor involvement results from spinal cord impingement on motor neurons.]
Carbohydrate Metabolism:

This glucose transporter is the primary transporter in hepatocytes. It is insulin-independent and allows the liver to respond appropriately to serum glucose concentrations.
GLUT-2

[Genetic deficiency of this important hepatic transporter results in type XI glycogen storage disease. Patients present much like those with von Gierke's disease, with hypoglycemia, ketonuria, and hypercholesterolemia.]
Carbohydrate Metabolism:

This diabetic medication works by inhibiting hepatic gluconeogenesis, thereby decreasing serum glucose levels.
Metformin

[Patients with type II diabetes have significantly increased rates of gluconeogenesis. Metformin, a member of the biguanide class of agents, is important in the treatment of type II diabetes, particularly in those with coexisting obesity.]
Carbohydrate Metabolism:

This class of agents, used in the treatment of type II diabetes, induces genes that increase the cell's responsiveness to circulating insulin.
Thiazolidinediones

[Diabetes is typically diagnosed when patients have fasting blood sugars above 126 mg/dL on two separate occasions. Alternatively, patients with blood glucose > 200 mg/dL on the oral glucose tolerance test are diagnosed with diabetes.]
Carbohydrate Metabolism:

This metabolite results from the conversion of the aldehyde group of glucose to an alcohol by the action of the enzyme aldose reductase.
Sorbitol

[This metabolite accumulates in cells, increasing the osmotic pressure and promoting cell swelling. Ultimately damage occurs, resulting in injury to nerves and the lens of the eye, accounting for some of the long-term complications of type II diabetes]
Carbohydrate Metabolism:

This blood group antigen results from the addition of N-acetylgalactosamine to the H substance of antigens on red blood cells.
A blood group antigen

[The addition of this moiety by N-acetylgalactosamine transferase occurs on the nonreducing end of the H antigen, a fructose linked to a galactose residue]
Carbohydrate Metabolism:

This blood group results from the transfer of galactose to the nonreducing end of the H substance found on the surface proteins of red blood cells.
B blood group

[Patients with the AB blood group possess both an N-acetylgalactosamine transferase (formation of an A antigen) and galactosyl transferase (formation of the B blood group antigen). Patients with the O blood group do not have either transferase and produce no additional modifications to the H antigen.]
Carbohydrate Metabolism:

This molecule is composed of a core protein with repeating disaccharides of uronic acid and glucosamine.
Heparin

[This therapeutically important glucosaminoglycan is used as an anticoagulant in the management of myocardial infarction and in the prevention of deep venous thrombosis]
Carbohydrate Metabolism:

This enzyme, activated by the Ca⁺2 efflux from the sarcoplasmic reticulum during muscle contraction, activates glycogen phosphorylase, thus liberating glucose monomers for use in glycolysis.
Phosphorylase kinase

[The genetic deficiency of this enzyme causes a type IX glycogen storage disease (GSD). The most common form is X-linked, resulting in hepatomegaly, growth retardation, and delayed motor development.]
Carbohydrate Metabolism:

This disorder results from a partial genetic deficiency of the liver isozyme that normally liberates glucose monomers from the nonreducing ends of glycogen.
Glycogen storage disease (GSD) type VI or Hers' disease

[Complete deficiency of glycogen phosphorylase, the enzyme that liberates glucose-1-phosphate from glycogen to maintain blood glucose during fasting, would be lethal. Instead, patients have a partial deficiency with mild hypoglycemia and, rarely, liver enlargement.]
Carbohydrate Metabolism:

This disorder results from a deficiency of a glucosyl 4:6 transferase that is important in forming the branches during glycogen synthesis.
Glycogen storage disease (GSD) type IV or Andersen's disease

[Results in glycogen with very long outer branches. Patients develop cirrhosis of the liver, with death occurring in early childhood.]
Carbohydrate Metabolism:

This key regulatory enzyme in the formation of glycogen transfers glucose residues from UDP-glucose to the nonreducing ends of a glycogen primer.
Glycogen synthase

[The genetic deficiency of this enzyme results in a type 0 GSD that manifests with fasting hypoglycemia as well as muscle cramping]
Carbohydrate Metabolism:

This important allosterically regulated enzyme of the glycolytic pathway represents the first committed step in glycolysis.
Phosphofructokinase I (PFK 1)

[This enzyme is activated by fructose 2,6 biphosphate and AMP and inhibited by ATP and citrate. Genetic deficiency of this enzyme results in a type VII GSD causing hemolytic anemia and muscle cramping.]
Carbohydrate Metabolism:

Formed as a side product of 1,3 biphosphoglycerate in red blood cells, this intermediate is capable of altering hemoglobin's affinity for oxygen.
2,3 Biphosphoglycerate (BPG)

[BPG decreases the affinity of hemoglobin for oxygen, thus facilitating oxygen release in tissues. Fetal hemoglobin has a lower affinity for BPG and therefore a higher affinity for oxygen, facilitating the transfer of oxygen from mother to fetus at the placental interface.]
Carbohydrate Metabolism:

This glycolytic enzymer converts 2-phosphoglycerate to phosphoenolpyruvate (PEP), which contains a high-energy enol phosphate.
Enolase

[This enzymer is inhibited by fluoride, which is used in samples collected for sensitive glucose tolerance testing, to prevent ongoing glycolysis]
Carbohydrate Metabolism:

This glycolytic enzyme isomerases the carbon sugar dihydroxyacetone phosphate to glyceraldehyde 3-phosphate.
Triose phosphate isomerase

[Although rare, a genetic deficiency of this enzyme results in neonatal onset hemolytic anemia, progressive neurologic impairment, and cardiomyopathy]
Carbohydrate Metabolism:

This protein cotransports sodium and glucose into the cell in an insulin-independent manner and is widely expressed on cells, although most abundantly on red blood cells.
GLUT-1

[As red blood cells lack mitochondria, they are completely reliant on glycolysis and are therefore insulin-independent. Hereditary deficiency of GLUT-1 has been reported, with decreased glucose in the cerebrospinal fluid, predisposing to the development of seizures.]
Carbohydrate Metabolism:

This pharmacologic agent inhibits the enzyme α-amylase and α-glucosidase, the enzymes that normally cleave the α-1,4 and α-1,6 linkages between dietary carbohydrates.
Acarbose

[This agent is used in the management of diabetes to slow the digestion of carbohydrates and thus to provide better postprandial control of blood glucose]
Oxidative Metabolism:

This fish poison complexes with NADH dehydrogenase, preventing NADH from transferring electrons to the electron transport chain for the production of ATP.
Rotenone

[However, rotenone does not block the transfer of electrons by FADH₂ at the level of coenzyme Q]
Oxidative Metabolism:

This compound binds to the Fe⁺3 of cytochrome aa₃ and inhibits complex IV of the electron transport chain, resulting in cessation of cellular respiration and rapid death.
Cyanide

[Cyanide poisoning can result from exposure to the poison through the production of CN⁻ from drugs such as nitroprusside. Victims often have the smell of "bitter almonds" on their breath.]
Oxidative Metabolism:

This molecule uncouples the electron transport chain and the production of ATP from ADP and Pi in the mitochondria, resulting in increased O₂ consumption and heat production.
DNP (DiNitroPhenol)

[2,4-DNP acts as an ionophore, allowing protons from the cytosolic side to reenter the mitochondrial matrix without passing through the F₁F₀-ATPase]
Oxidative Metabolism:

This condition results from the uncoupling of oxidative phosphorylation from electron transport, resulting in excess heat production in genetically susceptible individuals exposed to inhaled anesthetics.
Malignant hyperthermia

[This potentially lethal disorder is most commonly associated with exposure to halothane in patients with mutations in the ryanodine receptor of the sarcoplasmic reticulum]
Oxidative Metabolism:

This enzyme is important in hydroxylation reactions for the detoxification of many drugs in the liver as well as being implicated in converting potential carcinogens into more active forms.
Cytochrome P450

[This enzyme is related to the cytochromes instrumental in the electron transport chain and is found within the smooth endoplasmic reticulum, the site of drug detoxification; it is also instrumental in the formation of cholesterol and its derivatives]
Oxidative Metabolism:

This disorder results from a defect in the enzyme NADPH oxidase, resulting in the failure to produce superoxide anion (O₂⁻) from molecular oxygen.
Chronic granulomatous disease

[This is the most potent enzyme system utilized by neutrophils to destroy phagocytosed organisms, especially catalase-positive microorganisms]
Oxidative Metabolism:

Although typically benign, defects in this enzyme system result in impaired production of HOCl from H₂O₂ within the phagolysosomes of neutrophils.
MPO (myeloperoxidase) deficiency

[Because superoxide is such an efficient mechanism for microbial killing, defects in the production of HOCl (also used in microbial killing) are rarely appreciated clinically]
Oxidative Metabolism:

Exposure to this chemical leads to peroxidation of membrane lipids and the accumulation of fat within hepatocytes (fatty liver), eventually compromising the integrity of the lipid bilayer; the result is a massive influx of calcium and subsequent cell death.
CCl₄ (carbon tetrachloride)

[This chemical was once prevalent in the dry cleaning industry; it becomes toxic following the actions of the cytochrome P450 system, which converts CCl₄ + e⁻ to CCl₃· + Cl, creating the highly reactive toxic free radical CCl₃·]
Oxidative Metabolism:

This disorder can result from defects in the gene for superoxide dismutase (SOD), which normally catalyzes the reduction of superoxide anions to hydrogen peroxide.
ALS (Amyotrophic Lateral Sclerosis, Lou Gehrig's disease)

[This disorder results in progressive muscle atrophy due to deterioration of neurons of the corticospinal tracts and the upper motor neurons of the anterior horn of the spinal cord]
Oxidative Metabolism:

This thiamine-requiring multienzyme complex, located in the mitochondrial matrix, catalyzes the formation of acetyl-CoA from pyruvate.
Pyruvate dehydrogenase

[Deficiency of the components of this multienzyme complex causes neurodegenerative diseases ranging from mild ataxia and psychomotor delay to more lethal forms. Lactate accumulates in these patients, especially after high carbohydrate intake.]
Oxidative Metabolism:

This substance has approximately a 250-fold greater affinity for hemoglobin than oxygen and, with prolonged exposure, can cause asphyxiation.
Carbon monoxide

[Exposure can result in disorientation, headache, hyperreflexia, and cherry red mucous membranes due to the accumulation of carboxyhemoglobin]
Oxidative Metabolism:

This group of disorders often results in defects in components of the electron transport chain and displays a maternal inheritance pattern.
Mitochondrial myopathies

[This group of disease includes MELAS syndrome, manifesting with Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke; Leber's hereditary optic neuropathy, characterized by loss of central vision; and Kearns-Sayre syndrome, presenting with opthalmoplegia, pigmentary retinopathy, and cardiac conduction defects]
Oxidative Metabolism:

This compound inhibits one of the subunits of pyruvate dehydrogenase complex, resulting in impaired production of acetyl-CoA and subsequent oxidative phosphorylation.
Arsenic

[Arsenic is an odorless and tasteless heavy metal that has been used throughout the centuries as a poison]
Oxidative Metabolism:

This antibiotic-type compound binds to the stalk of ATP-synthase (the F₀ portion), preventing proton re-entry into the mitochondrial matrix.
Oligomycin

[Oligomycin, like 2,4-dinitrophenol, uncouples electron transport and ATP production, increasing the rate of respiration, electron transport, the TCA cycle, and CO₂ production while generating heat rather than energy]
Oxidative Metabolism:

This tripeptide compound, synthesized from glutamate, cysteine, and glycine, plays a role in reducing oxidized proteins as well as in the transport of amino acids across cell membranes.
Glutathione (GSH)

[Glutathione plays an important role in the detoxification of patients who overdose on acetaminophen. Such patients rapidly deplete GSH, which can be repleted by administering N-acetyl cysteine, or NAC.]
Oxidative Metabolism:

This enzyme produces an important oxidative metabolite through the conversion of L-arginine to citrulline; it is found in three isoforms in neuronal, macrophage, and endothelial tissues.
Nitric oxide synthase (NOS)

[In macrophages, NOS-2, or iNOS, is important in killing phagocytosed bacteria. Endothelial NOS, NOS-3, stimulates the influx of calcium into vascular endothelial cells with activation of cGMP, resulting in relaxation of vascular smooth muscle; it is also known as endothelial-derived relaxation factor, or EDRF.]
Oxidative Metabolism:

This biotin-requiring enzyme catalyzes the conversion of pyruvate to oxaloacetate, a key anaplerotic reaction of the tricarboxylic acid cycle
Pyruvate carboxylase

[Deficiency of this enzyme presents early with elevated levels of lactic acid in the blood because the conversion of pyruvate to oxaloacetate is blocked. Patients develop hypotonia, ataxia, and seizures.]
Lipid Metabolism:

This genetic disorder results from the deficiency of hexosaminidase A, with accumulation of GM2 gangliosides within neurons.
Tay-Sachs disease

[Occurs primarily in patients of Ashkenazi Jewish descent and is marked by the presence of a distinctive cherry-red spot on the macula; death usually occurs before age 4 due to mental and motor deterioration with blindness]
Lipid Metabolism:

This, the most common lysosomal storage disease, results from the deficiency of glucocerebrosidase, with accumulation of glucocerebrosides in macrophages.
Gaucher's disease

[Accumulations in macrophages result in a "wrinkled tissue paper" cytoplasm, and lead to hepatomegaly, erosion of the femoral head, and a mild anemia]
Lipid Metabolism:

This disorder results from the X-linked deficiency of α-galactosidase A, with accumulation of ceremide trihexoside.
Fabry disease

[Deficiency of this lysosomal enzyme results in angiokeratomas, or painful skin lesions, with death due to renal failure in early adulthood]
Lipid Metabolism:

A disorder that results from the deficiency of the lysosomal enzyme sphingomyelinase, with accumulation of sphingomyelin within phagocytes.
Neimann-Pick disease

[Marked histologically by the presence of "foamy histiocytes"; results in progressive hepatosplenomegaly and neurologic deterioration, with death by the age of 3]
Lipid Metabolism:

This condition results from the autosomal recessive deficiency of galactocerebroside β-galactosidase and the accumulation of galactosylsphingosine.
Krabbe disease
(Globoid cell leukodystrophy or galactosylceramide lipidosis)

[This leukodystrophy results from the accumulation of a molecule toxic to oligodendrocytes. Clinical consequences of demyelination include spasticity and rapid neurodegeneration, leading to death.
Lipid Metabolism:

An autosomal recessive disorder resulting from a deficiency of arylsulfatase, with the accumulation of sulfate-containing lipids within neurons.
Metachromatic leukodystrophy (MLD)
or
Arylsulfatase A deficiency

[Causes the demyelination of neurons and accumulation of sulfatides in macrophages, resulting in metachromatic shift of dyes used to stain histologic sections of tissues. Patients eventually develop loss of cognitive function and ataxia, hyporeflexia, and seizures.]
Lipid Metabolism:

This fatal disorder results from a defect in the import of enzymes into peroxisomes; the failure to produce such organelles leads to the accumulation of very long chain fatty acids and impaired production of bile acid.
Zellweger syndrome (Cerebrohepatorenal syndrome)

[Another member of the family of leukodystrophies, neurologic impairment results in death within the first year of age, with defects in the degradation of very long chain fatty acids and the formation of bile acids, which both take place partially within the peroxisome]
Lipid Metabolism:

This condition results from the inhibition of acetyl CoA dehydrogenase, with a reduced ability of fatty acids to be used as fuel and the development of severe hypoglycemia as glucose is depleted.
Jamaican vomiting sickness

[A potentially deadly disease due to the consumption of hypoglycin from unripe fruit of the ackee tree, causing inhibition of β-oxidation of fatty acids]
Lipid Metabolism:

Genetic defects in this enzyme lead to an inability to use long-chain fatty acids as fuel in skeletal muscle, with resultant myoglobinemia and weakness following exercise.
Carnitine acetyltransferase deficiency

[Normally acyl groups from fatty acids are transported from the cytosol into the mitochondrial matrix via the carnitine shuttle. Carnitine acetyltransferase I catalyzes the transfer of the acetyl moiety through a carrier attached to carnitine, where it is transferred back to CoA by carnitine acetyltransferase in the matrix.]
Lipid Metabolism:

This disorder results in the buildup of unesterified cholesterol, which is associated with particles of high-density lipoprotein (HDL).
Long-chain acyl-CoA dehydrogenase (LCAD) deficiency

[Esterified cholesterol is normally packaged by the liver into very low-density lipoprotein (VLDL) or converted to bile salts following the endocytosis of HDL. Accumulation of unesterified cholesterol results in corneal opacities, renal insufficiency, hemolytic anemia, and atherosclerosis.]
Lipid Metabolism:

This disorder results from a defect in the production of apolipoprotein A1, with subsequent absence of HDL.
Tangier disease
or
Familial α-lipoprotein deficiency

[In this disorder, cholesterol cannot be transported back to the liver, resulting in its accumulation within phagocytic cells and the development of neurologic problems and corneal opacities]
Lipid Metabolism:

Deficiency of this enzyme prevents the normal metabolism of medium-chain fatty acids via β-oxidation.
Medium-chain aceyl CoA dehydrogenase MCAD) deficiency

[Medium-chain fatty acids are normally absorbed into the portal blood; hypoglycemia results, and dicarboxylic acid produced by the co-oxidation of the fatty acids is excreted in the urine]
Lipid Metabolism:

This enzyme liberates arachidonic acid from membrane phospholipids for the creation of inflammatory mediators; it is inhibited by the administration of glucocorticoids.
Phospholipase A₂

[Arachidonic acid is the precursor for the formation of both leukotrienes and prostaglandins/thromboxanes; glucocorticoids therefore inhibit the production of both these major mediators of inflammation]
Lipid Metabolism:

This disorder results from the inadequate production by premature of the phospholipid dipalmitoylphosphatidylcholine.
Infant Respiratory Distress Syndrome (IRDS)
or
Hyaline membrane disease

[Dipalmitoylphosphatidylcholine is a constituent of surfactant, without which the premature lung becomes stiff and atelectatic]
Lipid Metabolism:

This enzyme is the rate-limiting step in the synthesis of cholesterol and is the main therapeutic target of drugs used in the treatment of hypercholesterolemia.
HMG-CoA reductase

[Hydroxymethylglutaryl (HMG)-CoA is formed by the condensation of acetyl CoA and acetoacetate in the cytoplasm, which is then converted by HMG-CoA reductase in smooth endoplasmic reticulum to mevalonate; the class of drugs known as statins are potent inhibitors of this step in the synthesis of cholesterol]
Lipid Metabolism:

A component of lipid membranes, this substance provides some rigidity to the fluid mosaic composed primarily of phosphoglycerides.
Cholesterol

[Patients with a condition known as spur cell anemia have increased cholesterol content in their membranes. The cells have decreased fluidity, making it difficult for them to pass through the spleen and resulting in anemia.]
Lipid Metabolism:

This artificial fat is composed of sucrose polyester and fatty acids, which cannot be degraded by gastric or pancreatic lipases; it therefore passes through the body undigested and unabsorbed.
Olestra

[Excess consumption can lead to deficiencies of fat-soluble vitamins as well as steatorrhea, or the passage of excess lipids in the feces]
Lipid Metabolism:

This pharmacologic agent, used to treat obesity, inhibits pancreatic and gastric lipases, resulting in reduced absorption of dietary fats.
Orlistat

[Pancreatic lipase, with the aid of colipase, plays a primary role in the digestion of fatty acids within the lumen of the small intestine after bicarbonate, also released from the pancreas, raises the pH of gastric contents to an optimal range]
Lipid Metabolism:

An autosomal recessive disorder resulting in the complete absence of circulating chylomicrons, VLDL, and LDL.
Abetalipoproteinemia
or
Bassen-Kornzweig syndrome

[Results from the deficiency of apoliproprotein B (apo B) and all particles in which apo B is found; this causes deficiencies of essential fatty acids and defects in lipid membranes, most evident with the appearance of acanthocytic erythrocytes, also known as burr cells]
Lipid Metabolism:

This disorder results from mutations in the apolipoprotein E gene, with increased serum triglycerides and cholesterol, leading to an increased likelihood of developing atherosclerosis.
Familial hyperlipidemia type III

[Apo E serves as a recognition factor on cell surface receptors; mutations prevent the reuptake of chylomicron and intermediate-density lipoproteins, resulting in the accumulation of lipids transported by them]
Lipid Metabolism:

A disorder due to mutations in the lipoprotein lipase gene, with a resultant increase in triglycerides and an increased likelihood of developing atherosclerosis.
Familial hypercholesterolemia type I

[Lipoprotein lipase is normally attached to vessel walls and liberated triglycerides from VLDL and chylomicrons for use by peripheral cells]
Lipid Metabolism:

One of the most common Mendelian disorders, this disease results from a defect in the cell surface receptor for the LDL receptor.
Familial hypercholesterolemia type II

{Heterozygotes occur in about 1 in 500 individuals and present with a double to triple elevation in plasma cholesterol; homozygotes have five to six times normal cholesterol; they may develop coronary artery disease and suffer a myocardial infarction before the age of 20]
Lipid Metabolism:

Results from a defect in transport proteins that carry long-chain fatty acids into the peroxisome to be metabolized.
Adrenoleukodystrophy (ALD)
or
Siemerling-Creutzfeldt Disease
or
Schilder's disease

[This X-linked neurologic disorder results from the accumulation of very long-chain fatty acids (VLCFA) in the brain (causing demyelination) and in the adrenal cortex (causing degeneration). Clinical manifestations include psychomotor retardation and seizures.
Amino Acid Metabolism:

Epithelial transport defect in the reabsorption of dibasic amino acids.
Cystinuria

[Failure to resorb cystine results in accumulation in the urine, with the potential for the development of cystine kidney stones]
Amino Acid Metabolism:

This genetic disorder is characterized by a defect in the absorption of essential neutral amino acids (e.g., tryptophan) due to a defect in epithelial transport proteins.
Hartnup disease

[Because tryptophan is a precursor to the vitamin niacin, symptoms of this disease are very similar to those of pellagra]
Amino Acid Metabolism:

This condition is due to the inability to convert histidine to urocanate, leading to elevated levels of histidine in the urine, which turn green with the addition of ferric chloride.
Histidinemia or Histidinuria

[Histidase normally converts histidine to urocanate, which is excreted in sweat; the association of this disorder with mental retardation is debatable]
Amino Acid Metabolism:

This disorder is most often due to defects in the enzyme cystathionine synthase, with a defect in the conversion of serine to form cysteine.
Homocystinuria

[Homocystinuria manifests itself with lens dislocations, mental retardation, and skeletal and neurologic abnormalities]
Amino Acid Metabolism:

This disorder results from a deficiency of the enzyme isovaleryl-CoA dehydrogenase and a defect in the oxidative decarboxylation of leucine.
Isoveleric acidemia

[Without dietary restriction of leucine, ketoacidotic episodes with a characteristic "sweaty feet" odor lead to neurologic involvement and developmental delay]
Amino Acid Metabolism:

This defect results from a deficiency of enzyme homogentisate oxidase, with the accumulation of homogentisate, the breakdown product of phenylalanine and tyrosine catabolism.
Alkaptonuria (ochronosis)

[Large amounts of homogentisic acid accumulate in the urine, which if allowed to stand, undergoes oxidation to a black color; deposition of blue-black pigmentation in articular cartilage results in degenerative arthritis]
Amino Acid Metabolism:

This disorder results primarily from defects in the enzyme phenylalanine hydroxylase, with failure of the conversion of phenylalanine to tyrosine.
Phenylketonuria

[Mandatory newborn screening in the United States allows early detection; dietary restriction of phenylalanine prevents the development of mental retardation]
Amino Acid Metabolism:

This disease is marked by the accumulation of branched-chain amino acids (valine, isoleucine, and leucine) due to a defect in the oxidative decarboxylation steps of catabolism of these amino acids.
Maple syrup urine disease

[Results in the accumulation of metabolites in the urine, imparting an odor of burnt sugar or maple syrup and leading to the development of neurologic impairment and mental retardation]
Amino Acid Metabolism:

This disorder results from a defect in the enxyme tyrosinase, with deficiency in the production of melanin from tyrosine.
Albinism

[The lack of melanin results in loss of pigmentation of the skin, hair, iris, and retina, with increased sensitivity to bright light, increased likelihood of sunburn, and the development of skin cancer]
Amino Acid Metabolism:

This neurotransmitter is produced by the decarboxylation of histidine and is important in acid secretion and the allergic response.
Histamine

[Binding of histamine to H₁ receptors in the stomach stimulates the release of gastric acid. Binding of histamine to H₂ receptors on basophils stimulates the release of inflammatory mediators of the allergic response.]
Amino Acid Metabolism:

This amino acid is the principal excitatory neurotransmitter in the brain and spinal cord.
Glutamic acid (glutamate)

[The drugs of abuse, such as ketamine and phencyclidine (PCP), antagonize glutamate neurotransmission. As well, memantine, a drug for Alzheimer's disease, interferes with glutamate neurotransmission.]
Amino Acid Metabolism:

This neutral amino acid functions as an important inhibitory neurotransmitter in the brainstem and spinal cord.
Glycine

[The actions of this neurotransmitter are antagonized by the rodenticide strychnine, exposure to which leads to twitching and muscle spasms]
Amino Acid Metabolism:

This enzyme, located in the mitochondria, catalyzes the first reaction of the urea cycle. It produces carbamoyl phosphate from NH₄⁺, CO₂, and 2 ATP.
Carbamoyl phosphate synthetase I

[A hereditary deficiency of this enzyme results in the inability to dispose of nitrogenous waste. Without strict dietary control, increased ammonia levels can lead to brain damage, coma, and/or death.]
Amino Acid Metabolism:

This enzyme of the urea cucle, located in the mitochondria, forms citrulline from ornithine and carbamoyl phosphate.
Ornithine transcarbomylase (OTC)

[The citrulline that is produced is transported into the cytosol for completion of the urea cycle. Without dietary control, a genetic deficiency of OTC leads to neurologic impairment and potential death due to ammonia accumulation.]
Amino Acid Metabolism:

This terminal enzyme of the urea cycle cleaves arginine to form urea and regenerates ornithine for a subsequent round of the cycle.
Arginase

[A deficiency of this enzyme, unlike other enzymes of the urea cycle, does not result in a buildup of ammonia, as arginine can be excreted in the urine, carrying with it two "waste" nitrogens]
Amino Acid Metabolism:

This enzyme degrades asparginine to NH₄⁺ and aspartate, which are further transaminated to oxaloacetate.
Asparaginase

[The malignant cells in acute lymphoblastic leukemia (ALL) are unable to produce asparagine. Recombinantly produced asparaginase is given to such patients to further rob the leukemic cells of circulating asparagine.]
Amino Acid Metabolism:

This vitamin B₁₂-requiring enzyme normally converts methylmalonyl CoA to succinyl CoA with accumulation of the precursor propionyl CoA, formed by the catabolism of isoleucine, threonine, and methionine.
Methylmalonyl CoA mutase

[If not controlled by strict dietary restrictions, the resultant disease, methylmalonyl acidemia, causes failure to thrive, vomiting, dehydration, developmental delay, and seizures]
Amino Acid Metabolism:

This enzyme normally converts trypsinogen to the active protease trypsin, which cleaves peptide bonds where the carboxy terminal amino acid is arginine or lysine.
Enterokinase

[Although trypsinogen is capable of autocatalysis, a deficiency of enterokinase, an important zymogen activator, can result in diarrhea, hypoproteinemia, and failure to thrive]
Amino Acid Metabolism:

This important indoleamine neurotransmitter is formed from the amino acid tryptophan.
Serotonin

[Serotonin is an important neurotransmitter in mood disorders. Selective serotonin reuptake inhibitors (SSRIs) promote the action of serotonin and are used in the treatment of depression. Melatonin, an important neurotransmitter in the pineal gland, is derived from serotonin.]
Amino Acid Metabolism:

This catecholamine neurotransmitter is formed from the amino acid tyrosine and is decreased in patients with Parkinson's disease.
Dopamine

[Patients with Parkinson's disease develop resting tumors and a shifting gait due to the destruction of dopamine-producing neurons. Therapy includes administering dopa, which is subsequently converted to dopamine by the enzyme dopa decarboxylase.]
Miscellaneous Nitrogen Metabolism:

This defect in purine nucleotide catabolism results from the failure in the conversion of inosine to hypoxanthine, as well as the conversion of guanosine to guanine, with a decreased production of uric acid.
Purine nucleoside phosphorylase deficiency

[This disorder results in an impairment of T-lymphocyte function but no defects in B-cell function. It also results indirectly in inhibition of the enzyme ribonucleotide reductase, resulting in inhibition of DNA synthesis.]
Miscellaneous Nitrogen Metabolism:

This disorder in the salvage pathway of purine nucleotide synthesis results from a complete deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), with the inability to salvage either hypoxanthine or guanine.
Lesch-Nyhan syndrome

[This X-linked disorder results from excess production of uric acid, with the subsequent development of gout, mental retardation, spasticity, and self-mutilation]
Miscellaneous Nitrogen Metabolism:

This disorder results in defective conversion of adenosine to inosine, with the subsequent accumulation of adenosine and its metabolites, which are toxic to lymphocytes.
ADA (adenosine deaminase) deficiency

[The subsequent loss of both T and B lymphocytes results in severe combined immunodeficiency (SCID). ADA deficiency was the first disease for which gene therapy in humans was attempted and succeeded.
Miscellaneous Nitrogen Metabolism:

This enzyme is the prime target of the drug allopurinol, used in the treatment of gout, to prevent the end production of uric acid from the degradation of purine nucleotides.
Xanthine oxidase

[Uric acid has a tendency to deposit as crystals, called tophi, in joints and soft tissue, resulting in recurrent attacks of acute arthritis. Allopurinol inhibits the conversion of xanthine to uric acid, with the resulting accumulation of xanthine and hypoxanthine, both of which are more soluble than uric acid.]
Miscellaneous Nitrogen Metabolism:

Results from the deficiency of the enzyme uroporphyrinogen decarboxylase, with the accumulation of uroporphyrin in the urine.
Porphyria cutanea tardia

[This is the most common of all of the hereditary porphyrias; unlike many, it is inherited as an autosomal dominant trait]
Miscellaneous Nitrogen Metabolism:

This autosomal dominant disorder is due to a deficiency of porphyrinogen deaminase, with the accumulation of porphobilinogen and δ-aminolevulinic acid in the urine.
Acute intermittent porphyria (patients have periodic attacks of abdominal colic, sometimes provoked by various drugs. Unlike many of the hereditary porphyrias, it does not cause photosensitivity.]
Miscellaneous Nitrogen Metabolism:

Exposure to this substance results in anemia, as it inhibits key enzymes-namely δ-aminolevulinic acid dehydratase and ferroketolase-in the synthesis of hemoglobin.
Lead

[Exposure can result from the ingestion or inhalation of dust or fumes and can result in renal toxicity, neuropathy, and cognitive defects. Lead accumulates in bones, forming radiodense lead lines at the epiphysis, especially in children.]
Miscellaneous Nitrogen Metabolism:

A relatively common and innocuous disorder resulting from quantitative deficiencies in the enzyme bilirubin-UDP transferase, with asymptomatic accumulation of unconjugated bilirubin.
Gilbert syndrome (GS)
or
Gilbert-Meulengracht syndrome

[2 to 10% of the population has only up to 30% of the normal level of bilirubin-UDP transferase, with hyperbilirubinemia found on routine laboratory exams, particularly following illness, strenuous exercise, or fasting]
Miscellaneous Nitrogen Metabolism:

This disorder results from a severe deficiency of the enzyme bilirubin-UDP-glucuronic acid transferase (UGT), with life-threatening accumulation of bilirubin.
Crigler-Najjar syndrome type I

[Without a liver transplant, this disorder is often fatal within the first 15 months of life. Crigler-Najjar syndrome type II is a less severe form resulting from decreased activity of the UGT enzyme.]
MIscellaneous Nitrogen Metabolism:

This condition results from the accumulation of unconjugated bilirubin, which-owing to its lipid solubility-has a tendency to cross the blood-brain barrier, with the potential to develop mental retardation.
Kernicterus

[This condition can result from hemolytic disease of the newborn or congenital disorders of bilirubin conjugation; it is often treated with phototherapy, which promotes the conversion of bilirubin to photoisomers, which are more readilty excreted in urine]
MIscellaneous Nitrogen Metabolism:

This defect can result from a deficiency of either domains of the single polypeptide of orotate phosphoribosyltransferase or orotidine 5'-monophosphate decarboxylase, leading to inability to produce pyrimidines.
Orotic aciduria

[This condition results in growth retardation, anemia, and immune compromise due to defects in DNA synthesis. Oral administration of uridine bypasses the metabolic block and provides a source of pyrimidines.]
MIscellaneous Nitrogen Metabolism:

This enzyme catalyzes the first step in both purine and pyrimidine synthesis, forming 5'-phosphoribosyl-1'pyrophosphate from ATP and ribose.
5'-Phosporibosyl-1'-pyrophosphate (PRPP) synthetase

[Overactivity of PRPP synthetase, due to a lack of feedback inhibition, is an X-linked disorder resulting in overproduction of nucleotides. It leads to increased degradation as well, resulting in hyperuricemia, gout, and kidney stones.]
MIscellaneous Nitrogen Metabolism:

This important enzyme in purine synthesis converts inosine monophosphate (IMP) to xanthosine monophosphate.
IMP dehydrogenase

[Mycophenolic acid is a powerful immunosuppressant and a reversible inhibitor of IMP dehydrogenase. This drug limits the formation of nucleic acids in activated and proliferating immune cells and is used in treating autoimmune disease as well as in preventing transplant rejection.]
MIscellaneous Nitrogen Metabolism:

This enzyme is required for the reduction of ribonucleotides to deoxyribonucleotides for the use in DNA synthesis.
Ribonucleotide reductase

[The antineoplastic agent hydroxyurea is an inhibitor of ribonucleotide reductase. It is used in the treatment of chronic myelogenous leukemia, polycythemia vera, and essential thrombocytosis.]
Molecular Endocrinology:

This endocrine tumor results in the overproduction of catecholamine neurotransmitters, such as norepinephrine, with the increased urinary excretion of its breakdown product, vanillylmandelic acid (VMA).
Pheochromocytoma

[Increased systemic circulation of catecholamines results in symptoms due to sympathetic hyperactivity, including hypertension, palpitations, and hyperglycemia]
Molecular Endocrinology:

This disorder results from a defect in the testosterone receptor protein with the phenotypic appearance of a female despite a 46XY karyotype.
Androgen insensitivity syndrome

[Without the virilizing effects of either testosterone or dihydrotestosterone, such patients develop breast tissue and a vagina that ends in a blind pouch, along with the presence of undescended testes, or cryptorchidism]
Molecular Endocrinology:

Deficiency of this enzyme, which normally converts pregnenolone to progesterone, results in a deficiency of glucocorticoids, mineralocorticoids, and androgens.
3-β-hydroxysteroid dehydrogenase deficiency

[This rare deficiency results in life-threatening salt-losing hypotension, with all patients having female external genitalia, regardless of sex, due to lack of androgens]
Molecular Endocrinology:

This synthetic form of ACTH is used to evaluate serum cortisol levels after administration to evaluate the presence of an intact hypothalamic-pituitary-adrenal (HPA) axis.
Cosyntropin

[Cortisol levels are evaluated after 30 and 60 minutes of administration. Abnormal results suggest adrenal insufficiency requiring administration of exogenous corticosteroids.]
Molecular Endocrinology:

This hormone is produced by the posterior pituitary in response to decreased blood volume or increased sodium concentration, stimulating the resorption of water by the kidney tubules.
Vasopressin
(Antidiuretic hormone, ADH)

[The syndrome of inappropriate ADH secretion, SIADH, results from trauma to the head, use of various medications, or ectopic production of ADH by a lung tumor. Patients are unable to dilute their urine, with resultant dilutional hyponatremia and reduced serum osmolality.]
Molecular Endocrinology:

Production of the hormone of the anterior pituitary is normally inhibited by dopamine. Its function is to stimulate the production of the milk proteins by the mammary glands in nursing mothers.
Prolactin

[Prolactinomas are the most common tumors of the pituitary. Patients present with double vision due to compression of the optic chiasm as well as amenorrhea and galactorrhea. Hyperprolactinemia can also result from drugs that inhibit dopamine's actions, including some antipsychotic medications.]
Molecular Endocrinology:

Deficiency of this important metabolic hormone results in a reduced basal metabolic rate with decreased ATP production, resulting in weakness, fatigue, and hypokinesis.
Thyroid hormone

[Hypothyroidism is confirmed by the presence of increased thyroid stimulating hormone (TSH) levels. Patients also present with cold intolerance, reduced heart rate, weight gain, constipation, and the development of brittle hair.]
Molecular Endocrinology:

This hypermetabolic condition results in a sense of heat intolerance, increased heart rate and systolic blood pressure, as well as weight loss despite increased caloric intake.
Hyperthyroidism

[Hyperthyroidism is most often due to Grave's disease, in which autoantibodies to TSH stimulate the release of excess T3 and T4. As a result, levels of TSH are decreased.]
Molecular Endocrinology:

This hormone, produced by the anterior pituitary, antagonizes many of the metabolic actions of insulin. It stimilates gluconeogenesis and promotes lipolysis while preserving muscle protein.
Growth hormone

[Excess growth hormone can result from a benign tumor of the pituitary gland. If hypersecretion begins prior to closure of the epiphyseal plates of long bones, gigantism occurs. If the condition occurs in adulthood, it leads to acromegaly, characterized by soft tissue overgrowth, with organomegaly, thickening of the skin, and coarsening of facial features.]
Molecular Endocrinology:

This condition results from an excess of aldosterone with development of sodium retention and potassium secretion and resultant hypertension and hypokalemia.
Conn syndrome
(Primary hyperaldosteronism)

[Primary hyperaldosteronism is most often the result of an aldosterone-secreting tumor of one of the adrenal glands. The synthesis of aldosterone in the glomerulosa cells of the adrenal cortex is stimulated by angiotensin.]
Molecular Endocrinology:

This mineralocorticoid deficiency leads to a net loss of sodium ions and water into the urine with a reciprocal retention of potassium ions (hyperkalemia) and hydrogen ions (mild metabolic acidosis).
Addison's disease

[A deficiency of adrenocortical secretion of aldosterone is usually accompanied by a reduction in the secretion of other adrenal steroid hormones as well. Subsequent contraction of the effective plasma volume may lead to a reduction in blood pressure. If volume loss is profound, perfusion of vital tissues, such as the brain, can lead to light-headedness and possible loss of conciousness.]
Molecular Endocrinology:

This enzyme is required for the production of dihydrotesterone (DHT) from testosterone, without which normal male development cannot occur.
5α-reductase

[A genetic deficiency of this enzyme results in a phenotype similar to that of androgen-insensitivity syndrome. Pharmacologic agents that inhibit this enzyme (e.g., finasteride) are used to inhibit some of the effects of DHT in normal men, including to prevent male-pattern baldness or benign prostatic hyperplasia, or BPH.]
Molecular Endocrinology:

This hormone is produced by the cells of the gastric antrum and the duodenum and stimulates the secretion of gastric acid and pepsin.
Gastrin

[Gastrinomas, gastrin-secreting endocrine tumors, are associated with Zollinger-Ellison syndrome. Hypergastrinemia results in increased HCl production, with resultant recurrent peptic ulcers.]
Molecular Endocrinology:

Most often due to the exogenous administration of glucocorticoids, this condition results in glucose intolerance, loss of muscle protein, osteoporosis, immunosuppression, and increased vascular fragility.
Cushing's syndrome

[Results in disposition of fat in the face, known as moon facies; in the posterior neck, known as buffalo hump; as well as in the thorax and abdomen while sparing the distal extremities, causes a distinct "central obesity." There may be thinning and tearing of dermal and epidermal structures, which manifests as reddish/purplish stripes, or striae, over the lower abdomen. Increased vascular fragility also results, with easy bruising. Cushing's disease refers to hypercortisolemia due to excessive secretion of ACTH by a pituitary tumor.]
Molecular Endocrinology:

Deficiency of this enzyme in steroid hormone synthesis results in the decreased production of cortisol and androgens but increased production of aldosterone.
17-α hydroxylase deficiency

[Male and female teenagers are usually diagnosed during puberty with lack of secondary sexual characteristics. Increased aldosterone can cause excessive salt absorption.]
Molecular Endocrinology:

Deficiency of this adrenal enzyme results in a block in the synthesis of both mineralocorticoids and glucocorticoids, and overproduction of androgens.
21-α hydroxylase deficiency

[This is the most common form of congenital adrenal hyperplasia. Patients have salt-losing hypotension. An excess of androgens leads to masculinization of female external genitalia and early virilization in males.]
Nutrition:

This condition results from a lack of the vitamin cofactor for the enzymes α-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase.
Beriberi
[Thiamin (Vitamin B₁) deficiency]

[Common in chronic alcoholics with poor diets, which results in Wernicke-Korsakoff encephalopathy, high-out heart failure, polyneuropathy, confusion, and nystagmus]
Nutrition:

This water-soluble vitamin is required for the production of flavin adenine dinucleotide (FAD) and is therefore important in several oxidative reactions of Krebs cycle.
Riboflavin (vitamin B₂)

[Deficiency of this vitamin results in cheilosis, corneal vascularization, glossitis, and dermatitis; it is rare in the United States, since breads and cereals are often supplemented with riboflavin]
Nutrition:

Deficiency of this water-soluble vitamin results in a deficiency of NAD⁺ and NADP⁺, with impaired glycolysis, citric acid cycle, and other oxidative processes.
Niacin (nicotinic acid, vitamin B₃)

[Deficiency is manifested clinically as pellagra, characterized by the "3 Ds": diarrhea, dermatitis, and dementia]
Nutrition:

Deficiency of this vitamin cofactor for the enzyme glutamic acid decarboxylase results in a deficiency of the neurotransmitter γ-aminobutyric acid (GABA).
Vitamin B₆ (pyridoxine)

[Clinical manifestations include infantile convulsions, neurologic dysfunction, as well as anemia, because pyridoxine is also required for the synthesis of δ-aminolevulinic acid from glycine and succinyl CoA]
Nutrition:

A deficiency of this vitamin results in decreased DNA and RNA synthesis, since it is a carbon donor for the synthesis of thymidine and purines.
Folate deficiency

[A deficiency of folate results in the development of megaloblastic anemia and increases the likelihood of the development of neural tube defects early in the development of neural tube defects early in the development of the fetus]
Nutrition:

A deficiency of this water-soluble vitamin results in defective collagen synthesis, since it is required for the hydroxylation of proline residues to form functional collagen fibers.
Vitamin C deficienct (scurvy)

[A deficiency of vitamin C results in defective bone formation, defects in collagen formation, abnormal bleeding, and poor wound healing]
Nutrition:

This water-soluble vitamin is required for the production of folate and therefore the production of precursors for nucleotide synthesis.
Vitamin₁₂

[A deficiency of vitamin B₁₂ mimics that of folate, but in addition to the megaloblastic anemia, a deficiency of vitamin B₁₂ can result in neurologic deficits, including subacute combined degeneration]
Nutrition:

Because ultraviolet (UV) light is required for the synthesis of its active form, deficiency of this fat-soluble vitamin is more likely to be found in northern latitudes, resulting in increased susceptibility to bone fractures (osteomalacia).
Vitamin D

[With exposure to UV light, the skin converts 7-dehydrocholesterol to cholecalciferol, which is first converted to 25-OH-vitamin D in the liver and then to active 1,25-(OH)₂, which acts on the cells of the kidney and intestine to increase reabsorption of calcium, required for proper bone remodeling]
Nutrition:

This disorder results in a failure to properly mineralize the matrix of type I collagen found in bone, resulting in weak bone formation in children during development.
Rickets

[A deficiency of vitamin D during childhood results in softening of the occipital and parietal bones (craniotabes), excess deposition of collagen along the costochondral junction (rachitic rosary), with depression of the chest along the diaphragm (Harrison's groove), and bowing of the legs (genu valgus and genu varus)]
Nutrition:

Dietary supplementation with this antioxidant free-radical-scavenging vitamin is associated with a decreased risk of coronary artery disease and delayed development of cataracts.
Vitamin E

[Rarely, deficiency of the most active form of vitamin E, α-tocopherol, may result in oxidative damage to red blood cells, degeneration of axons in the posterior columns of the spinal cord, and dying-back axonopathy of the cells in the dorsal root ganglion]
Nutrition:

A deficiency of this fat-soluble vitamin results in hemorrhagic disease, since it is required for the glutamyl carboxylation of several clotting factors.
Vitamin K

[Vitamin K is synthesized by intestinal microorganisms and is required for the production of clotting factors II, VII, IX, and X]
Nutrition:

A deficiency of this mineral results in the production of thyroid hormone, with the development of symptoms of hypothyroidism.
Iodine deficiency

[Iodine is required for the production of both forms of thyroid hormone, T3 and T4; a deficiency of iodine results in impaired metabolism with weight gain, cold intolerance, constipation, and slowed mentation]
Nutrition:

Impaired production of this substance results in defects in the absorption of vitamin B₁₂ from the digestive tract.
Intrinsic factor

[Intrinsic factor is produced by the parietal cells of the stomach, which may be lost in cases of autoimmune pernicious anemia or gastric resection, resulting in a secondary deficiency of vitamin B₁₂]
Nutrition:

This essential mineral is a vital component in the synthesis of hemglobin as well as other metallo-enzymes.
Iron

[Iron deficiency results in defective hemoglobin production, leading to the development of a hypochromic microcytic anemia]
Nutrition:

This nutritional disorder, more prevalent in the western world, is characterized by self-induced weight loss secondary to limited food intake.
Anorexia nervosa

[Those frequently affected include young, affluent, white women who, in spite of an emaciated appearance, often claim to be "fat." It is partially a behavioral problem; those afflicted are obsessed with losing weight. This is in contrast to bulimia, where patients partake in binges of overeating followed by self-induced vomiting to avoid gaining weight.]
Nutrition:

This nutritional disorder commonly occurs in children in third-world countries where the diet, which is adequate in calories, is low in protein.
Kwashiorkor

[A deficiency of dietary protein causes a decrease in protein synthesis that eventually affects the regeneration of intestinal epithelial cells; thus the problem is exacerbated by malabsorption. Hepatomegaly and a distended abdomen are often observed. This is in contrast to marasmus, which results from a diet deficient in both protein and calories.]
Nutrition:

This lipid-soluble vitamin is required for growth and differentiation as well as the production of the light-absorbing protein rhodopsin, essential to vision.
Vitamin A

[Deficiency results in night blindness, dry eyes leading to corneal damage, and urinary stones. Vitamin A toxicity causes the development of dry pruritic skin, cirrhosis of the liver, and increased intracranial pressure as well as vomiting; it is associated with excess dietary consumption of β-carotene.]
DNA, RNA and Proteins:

This structure is found at the 5' end of a transcribed RNA, conferring stability to the messenger RNA while increasing translation.
7-methyl guanine (7-MG) cap

[The N7 position of guanine is methylated. Viruses, such as influenza, transfer the 7-MG cap from the host cells mRNA to viral mRNA.]
DNA, RNA and Proteins:

This enzyme prevents extreme supercoiling of the parental DNA helix during replication as a consequence of unwinding DNA at the replication fork in eukaryotic cells.
Topoisomerase

[Etoposide, or VP-16, is an inhibitor of topoisomerase and is used in the treatment of numerous cancers. DNA gyrase is a prokaryotic topoisomerase that is inhibited by the antibiotic ciprofloxacin.]
DNA, RNA and Proteins:

This disorder results from the insertion of multiple CAG repeats within a protein, resulting in long stretched of glutamine (polyglutamine repeats) and leading to impaired protein function.
Huntington disease

[Aggregates of the dysfunctional protein accumulates in neuronal tissue, leading to atrophy of the caudate nucleus of the brain. Patients develop involuntary choreiform movements, depression, and cognitive impairment.]
DNA, RNA and Proteins:

These mobile genetic elements, known as "jumping genes," facilitate the movement of DNA segments from one site to another site.
Transposons

[Transposons in bacteria are believed to mediate the transfer of antibiotic resistance between bacteria. The creation of multi-drug-resistant organisms can result from such transfers.]
DNA, RNA and Proteins:

This enzyme is an RNA-dependent DNA-polymerase, producing a double-stranded DNA molecule from an RNA template.
Reverse transcriptase

[This enzyme is the target of many therapies for HIV, as the human immunodeficiency virus is a retrovirus. Hepatitis C also has a reverse transcriptase, which is a target of several therapies for infected patients.]
DNA, RNA and Proteins:

This bacterial antibiotic inhibits the beta subunit of bacterial DNA-dependent RNA polymerase.
Rifampin

[Bacterial RNA polymerase consists of four subunits α₁ββ' core enzyme, and a fifth subunit, sigma factor, required for initiation of RNA synthesis. Rifampin is used in treatment of tuberculosis as well as for prophylaxis for bacterial meningitis.]
DNA, RNA and Proteins:

This antibiotic-type compound binds to DNA and inhibits the elongation of RNA transcription by the RNA polymerase.
Actinomycin D

[This highly toxic compound is used in the treatment of some pediatric cancers, such as neuroblastoma, Wilms' tumor, and sarcomas.]
DNA, RNA and Proteins:

This toxin inhibits the production of heteronuclear RNA (hnRNA) by RNA polymerase II.
α-Amanitin

[Produced by Aminta phalloides, or the "death cap" mushroom, this substance causes gastrointestinal symptoms, liver toxicity, and possible death, as it ultimately halts protein synthesis.]
DNA, RNA and Proteins:

This disorder results from aberrant mRNA splicing of transcripts for the β-globin gene. Aberrant transcripts are degraded prior to translation, resulting in a quantitative deficiency of the protein.
β-Thalassemia

[Patients with mutations in one β-globin gene, thalassemia minor, manifest with mild anemia. Thalassemia major results from homozygous mutations; such patients have severe transfusion-dependent anemia.]
DNA, RNA and Proteins:

This disorder, which is among the most common genetic diseases, results from two well-known missence mutations in the HFE gene, coding for a protein involved in iron metabolism.
Hereditary hemochromatosis

[The two most common mutations are the C282Y mutation, resulting from a substitution of tyrosine for cysteine at amino acid 282, and the H63D mutation, with a substitution of aspartic acid for histidine at position 63. Patients develop cirrhosis, diabetes, skin pigmentation, and heart failure, with homozygous or compound heterozygous mutations.]
DNA, RNA and Proteins:

This enzyme recognizes a particular amino acid and the tRNA specific for that amino acid. It subsequently covalently attaches the amino acid to the 3' end of the cognate tRNA.
Amino-acetyl tRNA sythetase

[Patients with polymyositis have autoantibodies to histidyl-tRNA synthetase. They present with arthralgias and proximal muscle weakening.]
DNA, RNA and Proteins:

These classes of antibiotics bind to the 30S ribosomal subunit, interfering with the assembly of a functional ribosome.
Tetracyclines, aminoglycosides, and streptomycin

[Streptomycin binds to the 30S subunit, distorting the structure of the initiation complex. Tetracyclines block the access of amino-acetyl tRNA to the mRNA/ribosomal complex.]
DNA, RNA and Proteins:

These antibiotics inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria, inhibiting translocation of the growing peptide chain.
Erythromycin and clindamycin

[The50S ribosomal subunit has the P site, which contains the peptide, the A site, which binds the incoming amino acid. The peptide is elongated by covalent attachment of the peptide in the P site to the amino acid in the A site.]
DNA, RNA and Proteins:

This antibiotic inhibits the peptidyl transferase activity of the 50S ribosome, which normally transfers the peptide from the P site onto the next amino acid situated in the A site.
Chloramphenicol

[This antibiotic is rarely used, as it has been associated with the development of life-threatening aplastic anemia]
DNA, RNA and Proteins:

This toxin, elaborated by a bacterium, inactivates elongation factor EF-2, preventing translocation of the ribosome along the mRNA and inhibiting protein synthesis.
Diptheria toxin

[Produced from a phage gene incorporated into Corynebacterium diptheriae, this toxin inhibits EF-2 by adding ADP-ribose to the molecule. The resultant condition, diptheria, is a potentially fatal disease of the respiratory tract.]
DNA, RNA and Proteins:

This genetic phenomenon occurs in the T and B lymphocytes and results in the diverse repertoire of antibodies and T-cell receptors necessary for a functional immune system.
DNA rearrangement

[Such rearrangements result in the creation of a single transcriptional unit as segments of DNA move from one location to another, with the loss of intervening DNA]
DNA, RNA and Proteins:

This cytokine stimulates the synthesis of 2',5' oligo (A), which stimulates the degradation of mRNA; it also inhibits eukaryotic initiation factors.
Interferon-α

[This antiviral molecule is produced endogenously; it is also administered to patients with various viral diseases to prevent the spread of infection]
DNA, RNA and Proteins:

This hemoglobinopathy results from a point mutation in the beta chain of hemoglobin, with the substitution of valine for glutamine at the sixth amino acid position.
Sickle-cell anemia

[Patients with homozygous mutations form aggregates of polymerized deoxygenated hemoglobin; these deform the red blood cells, creating a sickle shape.. These cells are susceptible to hemolysis with the development of anemia and painful vasoocclusive crisis.]
DNA, RNA and Proteins:

This laboratory technique is used to detect and amplify nucleic acids for clinical and forensic testing.
Polymerase chain reaction (PCR)

[This technique can be used to detect the presence of nucleic acids in order to confirm viral infections, as in the case of hepatitis C. Among other applications is the detection of viral load in HIV-infected patients.]
DNA, RNA and Proteins:

In patient samples, this molecular technique is used to detect mutations that occur in restriction enzyme cleavage sites associated with genetic diseases.
Restriction fragment length polymorphisms (RFLP)

[RFLP is used in the diagnosis of sickle cell anemia, as the mutation in the disease results in abolition of the MstII restriction site in the β-globin gene, which can be detected with Southern blotting.]
DNA, RNA and Proteins:

This laboratory technique, based on antigen-antibody interactions, detects the presence of a protein in a clinical sample; it uses an enzyme that produces a chemiluminence product in the presence of the protein of interest.
Enzyme-linked immunosorbent assay (ELISA)

[This is commonly used as a screening test to determine whether infected patients are producing antibodies to HIV. The test is highly sensitive although not extremely specific for such infection.]
DNA, RNA and Proteins:

This molecular technique involves the separation of protein via electrophoresis and transfer to a membrane, followed by detection of cognate antigens with antibodies.
Western blot

[This test is used to confirm HIV infection in patients who have a positive ELISA test, as it is more specific. Antibodies to individual HIV proteins are found, with a final positive result requiring the detection of antibodies to two or more viral antigens.]
Genetics:

The karyotype 45, X0 of this disorder can be confirmed by the lack of a Barr body and an inactivated, condensed X chromosome in females, normally detected in a scraping of the inner cheek (buccal smear).
Turner syndrome

[Decreased levels of estrogens lead to female hypogonadism and the replacement of the ovaries by fibrous streaks; other congenital anomalies include coarctation of the aorta and the presence of a horseshoe kidney]
Genetics:

The karyotype of this disorder is 47, XXY. It is often due to a nondisjunction in the female gamete; thus there is an increased incidence with increasing maternal age.
Klinefelter syndrome

[These patiets have low testosterone levels and high levels of FSH, with atrophic testes, leading to infertility. They also lack secondary male characteristics, resulting in a eunuchoid appearance with gynecomastia.]
Genetics:

This condition results from the acquisition of a chromosome containing the long arm of chromosome 21 and another acrocentric chromosome, such as 22 or 14 in the maternal gamete.
Down syndrome due to a Robertsonian translocation

[Unlike most causes of Down syndrome, this cause is independent of maternal age and is frequently familial]
Genetics:

This disorder is due to a meiotic nondisjunction, resulting in trisomy 18.
Edward's syndrome

[Patients present with mental retardation, micrognathia, low-set ears, rocker-bottom feet, and congenital heart disease]
Genetics:

This disorder results from a meiotic nondisjunction, resulting in trisomy 13.
Patau syndrome

[Patients present with mental retardation, microphthalmia, cleft lip and palate, and polydactyly]
Genetics:

This condition results from the inheritance of a maternally derived chromosome 15, with a deletion of imprinted genes.
Angelman syndrome

[Patients present with mental retardation, ataxia, seizures, and inappropriate laughter,, leading to the term "happy puppet"]
Genetics:

This condition results from the deletion of genetically imprinted genes on the paternally inherited chromosome 15.
Prader-Willi syndrome

[Patients with this disorder present with mental retardation, short stature, hypogonadism, and obesity, as a result of a voracious appetite]
Genetics:

This group of hereditary disorders is characterized by transmission from mother to child in each generation but no transmission from the affected father.
Mitochondrial disorders

[The mitochondria has its own closed circular genome, which encodes 13 proteins for the inner membrane complexes, 22 tRNAs, and 2 rRNAs. The genetic code for the mitochondrial genome is slightly different that that used in the nucleus.]
Genetics:

These patients have an additional Y chromosome, resulting in a total of 47 chromosomes.
XXY syndrome

[Patients present as tall males with severe acne and sometimes mild retardation, mistakenly described in the past as occuring with increased incidence among violent criminals]
Genetics:

Trinucleotide repeat disorder leading to the expansion of the FMR1 gene, leading to a defect in the long arm of the X chromosome, resulting in chromosomal breakage in vivo.
Fragile X syndrome

[This important genetic cause of mental retardation is second only to Down syndrome. Patients have distinctly long faces as well as large mandibles, large ears, and large testicles (macroorchidism.]
Genetics:

This condition results from a small deletion of chromosomal DNA on band 11 on the long arm of chromosome 22 (22p11).
DiGeorge syndrome

[Patients with this disorder present with Congenital heart defects, Abnormal facies, T-cell deficiencies, Cleft palate, and Hypocalcemia, which can be remembered with the acronym CATCH-22]
Genetics:

This, the most common chromosomal disorder, is associated with maternal meiotic nondisjunction of chromosome 21.
Down syndrome

[Its incidence is related to increased maternal age. Down syndrome patients have an increased incidence of ventricular septal defects, acute leukemias, and early-onset Alzheimer disease.]
Genetics:

This condition results from the genetic deletion of DNA from the short arm (p) of chromosome 5.
Cri-du-chat (5p- "cry of the cat") syndrome

[These patients present with severe mental retardation, microcephaly, ocular hypertelorism, and an unusual cat-like cry]
Biochemistry of Cancer:

This important tumor suppressor gene, a nuclear phosphoprotein, normally inhibits cell cycle progression at the G₁/S boundary by inhibiting the transcription factor E₂F.
Rb (retinoblastoma)

[The Rb gene product nicely demonstrates Knudson's "two hit" hypothesis, in which patients develop tumors of the eye (retinoblastoma) and bone (osteosarcoma), as they must only undergo one additional mutation. Normal individuals must undergo separate mutations in both alleles in the same issue for sporadic tumors to occur.]
Biochemistry of Cancer:

Should cytochrome c be released from the outer membrane of the mitochondria in response to changes in membrane permeability, this antiapoptotic gene functions by inhibiting the irreversible cascade of apoptosis.
bcl-2

(Cytochrome c is capable is activating programmed cell death. Various cancers, such as follicular lymphomas, are associated with over-expression of bcl-2 and the development of cancer as a result of impaired apoptosis.]
Biochemistry of Cancer:

Mutation in these tumor suppressor genes, involved in DNA repair, are associated with familial clustering in the development of breast and ovarian cancer.
BRCA-1 and BRCA-2

[Although familial forms of breast cancer account for only 5 to 10% of all breast cancer cases, mutations in these two genes are associated with 80% of familial cases. Therefore the presence of breast cancer in a first-degree relative requires consideration as a risk factor in the development of breast cancer.]
Biochemistry of Cancer:

Mutations in this gene, located on chromosome 5, lead to loss of intracellular adhesiveness and the development of multitudes of precancerous polyps in the colon.
APC (adenomatous polyposis coli)

[This autosomal dominant condition gives rise to thousands of precancerous polyps in the colon, and one polyp or more will undergo malignant transformation, resulting in the development of colon cancer]
Biochemistry of Cancer:

This disorder results from defects in mismatch repair genes during DNA replication, allowing erroneous base pairing between nucleotide bases, with the accumulation of mutations on several genes over time.
HNPCC (hereditary non-polyposis colon cancer) syndrome

[Individuals with this autosomal recessive condition have an increased tendency to develop familial carcinomas of the colon]
Biochemistry of Cancer:

This disorder results from mutations in the tumor suppressor gene p53, which is often referred to as the "guardian of the genome," since p53 senses DNA damage, triggers cell cycle arrest and DNA repair, or triggers apoptosis in the event that damage is too severe.
Li Fraumeni syndrome

[This disorder is characterized by an increased tendency to develop sarcomas, breast cancer, leukemias, and brain tumors at a young age. The p53 gene is the one most commonly mutated in cancer, giving rise to nearly 50% of all sporadic tumors.]
Biochemistry of Cancer:

This protein is the most commonly mutated oncogene found in humor tumors, and normally functions as a mitogen-responsive GTPase.
Ras

[Mutations in this gene are found in 10 to 20% of all tumors, with greater frequency found in tumors of the colon, pancreas, and thyroid. Ras is usually active when bound to GTP; it can hydrolyze GTP to GDP, with subsequent inactivation. The most common mutations, codon 12 mutations, result in the loss of GTPase activity can constitutive ras activity.]
Biochemistry of Cancer:

This disorder is closely associated with the translocation between chromosomes 9 and 22, with the expression of the fusion protein bcr-abl.
Chronic myelogenous leukemia (CML)

[This aberrant proliferation of immature white blood cells results from the increased growth-promoting activity of the tyrosine kinase bcr-abl, which results from the translocation between chromosomes 9 and 22, or the Philadelphia chromosome]
Biochemistry of Cancer:

This hereditary syndrome causing a defect in DNA repair results from an inability to repair ultraviolet (UV) light-induced pyrimidine dimers.
Xeroderma pigmentosum

[This autosomal recessive disorder is characterized by a 2,000-fold increase in the development of skin cancer due to sun exposure]
Biochemistry of Cancer:

This disorder results from a defect in normal cell cycle arrest following exposure to mutagenic ionizing radiation, with continuation of DNA synthesis and the accumulation of genetic mutations.
Ataxia telangiectasia

[These patients are susceptible to the development of x-ray-induced (due to radiologic procedures) lymphoid maldevelopment (immunodeficiency or lymphoid malignancy) as well as loss of Purkinje cells in the cerebellum, with gait disturbances (ataxia)]
Biochemistry of Cancer:

This disorder results from a defect in a GTPase-activating protein(GAP), which is normally involved in catalyzing the hydrolysis of GTP by ras, thus shutting off the growth-promoting actions of ras.
Neurofibromatosis (von Recklinghausen disease)

[This autosomal dominant disorder, due to mutations in the NF-1 gene on chromosome 17, manifests with multiple neurofibromas, café-au-lait spots, Lisch nodules, and an increased risk of other tumors]
Biochemistry of Cancer:

This anticancer drug inhibits the cytoskeletal remodeling required to separate the sister chromatids that align at the equatorial plane of the cell during mitosis.
Paclitaxel (Taxol)

[This drug is used in the treatment of many cancers, including breast cancer]
Biochemistry of Cancer:

Over-expression of this receptor tyrosine kinase leads to growth-promoting signals in the absence of ligand, resulting in breast cancer.
HER2/Neu

[This gene becomes amplified in some breast cells resulting in autophosphorylation of intracellular domains of the receptors and activation of subsequent signaling cascades. The monoclonal antibody herceptin blocks receptor dimerization, thus preventing signaling, and is used in the treatment of some breast cancers.]
Biochemistry of Cancer:

This orally active small molecule selectively inhibits signal transduction by the epidermal growth factor (EGF) receptor.
Geftinib (Iressa)

[This drug is used in the treatment of non-small cell lung cancer of the lung; it is being actively explored for the treatment of other cancers]
Biochemistry of Cancer:

This orally active drug inhibits the tyrosine kinase activity of the p210 protein (the product of the bcr-abl oncogene) in chronic myelogenous leukemia.
Imatinib (Gleevec]

[This drug, developed on the basis of the concept of rational drug design, inhibits the potent tyrosine kinase p210, which is formed from the 9:22 translocation, or the Philadelphia chromosome]
Biochemistry of Cancer:

Exposure to this carcinogen acts synergistically with hepatitis B in the development of hepatocellular carcinoma.
Aflatoxin B₁

[This substance is produced by molds that grow on desperately needed grains consumed by many starving people in underdeveloped nations]
Biochemistry of Cancer:

This virus produces proteins that disturb the cell cycle, one that facilitates the degradation of cellular p53, and another that interferes with the tumor suppressing affects of the retinoblastoma protein.
Human papillomavirus (HPV)

[This DNA virus is associated with cervical cancer. The cellular changes of virally infected cells can be detected on Papanicolau (Pap) smear. Viral E6 interferes with p53 and viral E7 inhibits RB.]
Biochemistry of Cancer:

This DNA virus is the leading cause of hepatocellular carcinoma worldwide.
Hepatitis B virus (HBV)

[It is believed that repeated viral damage to liver cells followed by regeneration leads to increased accumulation of mutations, ultimately resulting in liver cancer]
Biochemistry of Cancer:

This growth factor is produced under hypoxic conditions in tumors, promoting vascularization of the growing mass.
Vascular endothelial growth factor (VEGF)

[Bevacizumab (Avastin) is a monoclonal antibody that inhibits VEGF, thus also inhibiting blood vessel formation. It is used in the treatment of colon and breast cancer as well as other solid tumors.]
Biochemistry of Cancer:

This estrogen antagonist is used in hormonal therapy in the treatment of breast cancer.
Tamixfen

[This drug binds to estrogen receptors and inhibits the growth-promoting effects of estrogens on breast cancers that over-express estrogen receptors]
Markers of Disease:

This enzyme, particularly abundant in skeletal and heart muscle, is involved in the transfer of high-energy phosphate and may indicate muscle damage or myocardial infarction when found in high levels in the serum.
Creatinine kinase (CK)

[This enzyme catalyzes the transfer of high-energy phosphate from ATP to the reservoir of creatinine to form creatinine phosphate in muscle and other tissue; there are three isoforms: CK-MM in skeletal muscle, CK-BB in the brain, and CK-MB in the heart]
Markers of Disease:

This enzyme transfers the amino group from glutamate to oxaloacetate to form aspartate; with liver damage, it can be found in the serum.
Aspartate aminotransferase (AST)

[This enzyme, also known as serum glutamate oxaloacetate transaminase (SGOT), is abundant in the cytoplasm and mitochondria of liver cells. In alcoholic cirrhosis, the AST/ALT ratio is often > 2.]
Markers of Disease:

Elevated serum levels of this amino acid are associated with the development of coronary artery disease.
Homocysteine

[Patients with high levels of homocysteine are advised to supplement their diet with folate, as it is a cofactor in the conversion of homocysteine to methionine]
Markers of Disease:

This protease is normally produced by prostatic epithelial cells and is elevated in both benign and prostatic hyperplasia (BPH) and prostate cancer.
Prostate-specific antigen (PSA)

[Unlike other tumor markers, used only to follow therapy after diagnosis, this tumor marker is a legitimate cancer screening marker in the fight against prostate cancer]
Markers of Disease:

As one of the only pancreatic enzymes that is not produced as a proenzyme, this enzyme is released during acute pancreatitis, resulting in the digestion of cell membranes.
Lipase

[Lipase released during injury to the pancreas digests lipid membranes, which readily form calcium soaps, a process known as saponification, with resultant hypocalcemia]
Markers of Disease:

This enzyme, produced by the salivary glands as well as the pancreas, cleaves α-1,4 linkages between glucose residues.
Amylase

[Serum amylase is elevated in cases of pancreatitis and is often measured in patients to evaluate such a condition. However, serum lipase is another marker of pancreatitis that demonstrates higher sensitivity and specificity than amylase.]
Markers of Disease:

Levels of this serum protein, which results from the non-enzymatic addition of sugar to protein, provides a measure of long-term glucose control in diabetic patients.
HbA1c

[Glycated hemoglobin, HbA1c, is normally 6% of the total hemoglobin, but it increases when red blood cells are exposed to high levels of blood glucose. Non-enzymatic glycation of proteins, from elevated circulating glucose, results in many of the complications of diabetes.]
Markers of Disease:

This peptide is liberated by the proteolytic cleavage of proinsulin to form the α and β chains, which are subsequently linked by disulfide bonds to form the mature hormone.
C-peptide

[C-peptide levels are used to differentiate the causes of a high insulin level. In patients with tumors of pancreatic β cells, serum levels of C-peptide will be elevated. However, in cases of surreptitious insulin administration (purposeful injection of insulin) C-peptide is not elevated, as commercial insulin preparations have purified away this contaminant.]
Markers of Disease:

This enzyme is involved in the transfer of amino acids across cell membranes and the transfer of glutamyl groups from peptides and other compounds to an acceptor.
Gamma glutamyl transferase (GGT)

[Elevated serum levels of GGT are seen with intra- and post-hepatic biliary obstruction, indicating cholestasis, and in some primary neoplasms as well as pancreatic cancer and alcohol-induced liver disease]
Markers of Disease:

This hormone is initially produced by the developing embryo after fertilization to maintain the corpus luteum.
Human chorionic gonadotropin (hCG)

[Over-the-counter pregnancy tests detect the presence of hCG in the urine. Serum quantitation of hCG levels can be used to differentiate a normal intrauterine pregnancy from an ectopic pregnancy.]
Markers of Disease:

This enzyme normally converts pyruvate to lactate, regenerating NAD⁺ for use in glycolysis. It is composed of four subunits and occurs in five isoforms.
Lactate dehydrogenase (LDH)

[LDH-2 (HHHM) is the predominant form found in serum, mostly due to the turnover of immune cells. In myocardial infarction (MI), LDH-1 (HHHH) becomes elevated over the normal levels of LDH-2, the so-called LDH flip. Although this marker has been replaced by better markers of MI, LDH does still have some value in diagnosing lymphomas as well as determining the etiology of pleural effusions.]
Markers of Disease:

This molecule results from the spontaneous cyclization of creatine phosphate, the high-energy storage molecule in muscle.
Creatinine

[The amount of creatinine excreted per day depends on body muscle mass and kidney function and is constant at about 15 mmol for the average person. Creatinine is an important marker of kidney function and rises sharply in cases of kidney failure.]
Markers of Disease:

This enzyme transfers the amino group from glutamate to pyruvate to form alanine and can be found in the serum of patients with liver damage.
Alanine aminotransferase (ALT)

[This enzyme, also known as serum glutamate pyruvate transaminase, or SGPT, is abundant in the cytoplasm of liver cells and is increased when liver cells are damaged, as in cirrhosis, or in liver tumors]