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365 Cards in this Set

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  • Back
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Glucose -> G6P, an irreversible regulatory step in glycolysis is catalyzed by which enyzme?
glucokinase/hexokinase
Fructose 6-phosphate -> F1,6BP, an irreversible regulatory step in glycolysis is catalyzed by which enyzme?
Phosphofructokinase (PFK)
Phosphoenolpyruvate (PEP)->pyruvate, an irreversible regulatory step in glycolysis is catalyzed by which enyzme?
pyruvate kinase
Acetyl CoA --> Citrate, an irreversible regulatory step in the TCA cycle is catalyzed by which enyzme?
citrate synthase
a-ketoglutarate -> succinate, an irreversible regulatory step in the TCA cycle is catalyzed by which enyzme?
a-ketoglutarate dehydrogenase
How many ATP are produced from one glucose molecule in anaerobic glycolysis?
2 ATP produced
How many ATP are produced from one glucose molecule in aerobic metabolism?
38ATP from malate shuttle
36 ATP from Glucose 3 phosphate shuttle
What is the product of the hexose monophospate shunt (HMP)?
NADPH used in anabolic processes (steroid and fatty acid synthesis) and ribose 5-phosphate for nucleotide synthesis
What molecules are universal electron acceptors?
Nicotinamides (NAD, NADP)
Flavin nucleotides (FAD)
NADs and FADs
Where is hexokinase found?
ubiquitous
What are the kinetic characteristics of hexokinase in relation to glucose?
high affinity, low capacity
hexokinase the the enzyme that converts glucose to G6P in glycolysis
What product inhibits hexokinase?
Glucose 6-Phosphate
hexokinase the the enzyme that converts glucose to G6P in glycolysis
Where does one find glucokinase?
in the liver
glucokinase phosphorylates excess glucose to sequester it in this organ
What are the kinetic characteristics of glucokinase in relation to glucose?
low affinity, high capacity
ensures that it only takes up glucose if there is great excess (e.g., after a meal)
Where does glycolysis occur in the cell?
Cytoplasm
Which enzyme is activated in the fasting state converting fructose-6-phosphate to fructose 2,6-bisphosphate?
PFK2
Which enzyme is activated in the fed state converting fructose-2,6-bisphosphatase to fructose 6-phosphatate?
fructose bisphosphatate-2
What molecule is the most potent activator of phosphofructokinase, converting fructose-6-phosphate to fructose 1,6-phosphate
Fructose 2,6 BP
A deficiency of which glycolytic enzyme is associated with hemolytic anemia?
pyruvate kinase

G6PDH is not part of glycolysis, it is part of the HMP shunt
RBCs metabolize glucose anaerobically (no mitochondria) thus solely depend on glycolysis
What are the only two purely ketogenic amino acids?
Lysine and Leucine
What factors increase the activation of the pyruvate dehydrogenase complex?
Low ATP/ADP ratio (exercise)
high NAD/NADH ratio
high IC [Ca]
you want to activate the TCA cycle when energy stores are low
How many ATP equivalents are needed to generate glucose from pyruvate?
6 ATP equivalents
What are the 4 fates for pyruvate at the end of glycolysis?
1. Alanine
2. oxaloacetate
3. Acetyl CoA
4. Lactate
1. used to carry amino groups to the liver from muscle
2. replenish TCA cycle or gluconeogenesis
3. transition from glycolysis to TCA cycle
4. end of anaerobic glycolysis
What is the function of the Cori cycle?
transfers excess reducing equivalents from RBCs and muscle to the liver; shifts the metabolic burden to the liver
muscles will be able to function anaerobically
What are the steps in the TCA cycle?
Citrate > isocitrate > a-ketoglutarate > succinyl CoA > succinate > fumate > malate > OAA
Can I Keep Selling Sex For Money, Officer?
What cofactors are required for the a-ketoglutarate dehydrogenase complex?
B1, B2, B3, B5, lipoic acid
Same as pyruvate dehydrogenase complex
Which complexes bring protons across the inner mitochondrial membrane?
Complexes I, III, IV
In oxidative phosphorylation, how many ATP are produced from 1 NADH?
3 ATP
In oxidative phosphorylation, how many ATP are produced from 1 FADH2?
2 ATP
What are the three categories of oxidative phosphorylation poisons?
1. e- transport inhibitors
2. ATPase inhibitors
3. Uncoupling agents
1. rotenone, CN-, CO
2. oligomyin
3. aspirin, 2-4-DNP
What are the 4 irreversible enzymes of gluconeogenesis and where are they located?
1. Pyruvate carboxylase (mitochondria)
2. PEP carboxykinase (PEPCK, cytosol)
3. Fructose 1,6-bisphosphatase (cytosol)
4. Glucose 6-phophotase (ER)
Pathway Produces Fresh Glucose
What tissues contain the irreversible enzymes of gluconeogenesis?
liver, kidney, intestinal epithelium

muscle does not contain G6Ptase and cannot participate in gluconeogenesis
Deficiency of key gluconeogenic enzymes causes what symptoms?
hypoglycemia
The HMP shunt occurs in what parts of the body?
lactating mammary glands, liver, adrenal cortex
all sites of fatty acid or steroid synthesis
In what part of the cell does the HMP shunt occur?
cytoplasm
What enzyme is required for the irreversible reaction of the HMP shunt producing NADPH?
Glucose-6-phosphate dehydrogenase
What is the product of the reversible reaction of HMP shunt?
Ribose-5-phosphate (for nucleotide synthesis) and Glyceraldehyde 3-phosphate, fructose 6-phosphate(intermediate of gyloslysis)
GLUT2 receptors are found in which cells?
b-cells in the pancreas, Liver, kidney
GLUT4 receptors are found in which cells?
Muscles and Fat
What is the general function of insulin?
-moves glucose into cells
-inhibits glucagon secretion from a-cells in pancreas
INsulin moves glucose INto cells
Which organs do not require insulin for glucose uptake?
Brain
RBCs
Intestine
Cornea
Kidney
Liver
BRICK L
What are the anabolic effects of insulin?
increased glucose transport
increased glycogen synthesis and storage
increased triglyceride synthesis and storage
increased Na retention
increased protein synthesis
What is the role of glycogen in skeletal muscle?
rapidly metabolize glucose during exercise
What is the role of glycogen in hepatocytes?
storage depot to maintain blood sugar at appropriate levels.
What are the main reactions of glycogenesis/degradation?
G6P > G1P > UDP-glucose > branched version > limit dextran > debranched glycogen
What are the 4 glycogen storage diseases?
Von Gierke's Dz (Type I)
Pompe's Dz (Type II)
Cori's Dz (Type III)
McArdle's Dz (Type V)
Very Poor Carbohydrate Metabolism
What are the findings of Von Gierke's Dz?
severe fasting hypoglycemia, high glycogen in the liver, increased blood lactate, hepatomegaly
The liver becomes a muscle (think about it)
What is the deficient enzyme in Von Gierke's Dz?
Glucose-6-phosphate
What are the findings of Pompe's dz?
cardiomegaly and systemic findings leading to early death
Pompe's trashes the pump (heart, liver and muscle)
What is the deficient enzyme in Pompe's Dz?
Lysosomal a-1,4-glucosidase (acid maltase)
What are the findings of Cori's disease?
Milder form of Van Gierke's (Type I) with normal blood lactate levels
What is the deficient enzyme in Cori's Dz?
debranching enzyme (a-1,6-glucosidase
What are the findings of McArdle's dz (Type V)?
increased glycogen in muscle but cannot break it down -> painful cramps and myoglobinuria with strenuous exercise
McArdles=Muscle
What is the deficient enzyme in McArdle's Dz?
skeletal muscle phosphorylase
A full-term neonate of uneventful delivery becomes mentally retarded and hyperactive and has a musty odor. What is the dx?
PKU
A stressed executive comes home from work, consumes 7 or 8 martinis in rapid succession before dinner, and becomes hypoglycemic. What is the mechanism?
Increase in NADH prevents gluconeogenesis by shunting pyruvate and oxaloacetate to lactate and malate
A 2 year-old girl has an increase in abdominal girth, failure to thrive, and skin and hair depigmentation. What is the dx?
Kwashiorkor
Alcoholic develops a rash, diarrhea, and altered mental status. What is the Vitamin Deficiency?
Vitamin B3 (pellagra)
A 51-year-old man has black spots in his sclera and has noted that his urine turns black upon standing. What is his dx?
Alkaptonuria
A 25-year-old male complains of severe chest pain and has xanthomas of his Achilles tendons. What is the dz and where is the defect?
Familial hypercholesterolemia; LDL receptor
A woman complains of intense muscle cramps and darkened urine after exercise. What is the dx?
McArdle's Dz
Two parents with albinismhave a sone who is normal. Why is the son not affected?
Locus heterogeneity
A 40-year-old man has chronic pancreatitis with pancreatic insufficiency. What vitamins are likely deficient?
A,D,E,K
What are the fat soluble vitamins?
A,D,E,K
What two organs contribute most to the absorption of fat-soluble vitamins?
gut (ileum) and pancreas
What dzs can cause fat soluble vitamin deficiencies?
Malabsorption syndromes such as CF, celiac sprue; miner oil intake can also cause deficiencies
Which vitamins are water soluble?
B1, B2,B3,B5,B6,B12,C,Biotin,Folate
Which water soluble vitamin does NOT wash out of the body easily and why?
Vit B12 because it is stored in the liver
What are some common symptoms of B-complex deficiencies?
dermatitis, glossitis, and diarrhea
What is another name for Vitamin A?
Retinol
Retin-A skin treatment
A deficiency in Vitamin A causes what symptoms?
night blindness, dry skin
What is the function of Vitamin A?
constituent of visual pigments
Excess of Vitamin A causes what symptoms?
arthralgias, fatigue, headaches, skin changes, sore throat, alopecia
What is another name for Vitamin B1?
thiamine
A deficiency in Vitamin B1 causes what symptoms?
BeriBeri and Wernike-Korsakoff syndrome
see it in alcoholics and malnutrition
What is the function of Vitamin B1?
a cofactor for oxidative decarboxylation of a-keto acids and a cofactor in the HMP shunt
What is another name for Vitamin B2?
riboflavin
A deficiency in Vitamin B2 causes what symptoms?
angular stomatitis, Cheilosis, corneal vascularization
the 2 C's
What is the function of Vitamin B2?
Cofactor for oxidation and reduction (e.g., FADH2)
B2 = 2 ATP
What is another name for Vitamin B3?
niacin
A deficiency in Vitamin B3 causes what symptoms?
Pellagra: diarrhea, dermatitis, dementia
The 4 D's of B3 Deficiency: drunks, diarrhea, dermatitis, dementia
What is the function of Vitamin B3?
Constituent of NAD, NADP (redox rxns); derived from tryptophan
What is another name for Vitamin B5?
pantothenate
5=pento=panto
A deficiency in Vitamin B5 causes what symptoms?
dermatitis, enteritis, alopecia, adrenal insufficiency
What is the function of Vitamin B5?
Constituent of CoA and component of FA synthase
A deficiency in Vitamin C causes what symptoms?
Scurvy - swollen gums, bruising, anemia, poor wound healing
What is the function of Vitamin C?
needed for the hydroxylation of proline and lysine in collagen synthesis; keeps Fe+2 in a reduced state increaseinf Fe absorption; cofactor for DA->NE
Vitamin C Cross-links collagen
A deficiency in Vitamin A causes what symptoms?
night blindness, dry skin
What is the function of Vitamin A?
constituent of visual pigments
Excess of Vitamin A causes what symptoms?
arthralgias, fatigue, headaches, skin changes, sore throat, alopecia
What is another name for Vitamin B1?
thiamine
What is the function of Vitamin B1?
a cofactor for oxidative decarboxylation of a-keto acids and a cofactor in the HMP shunt
What is another name for Vitamin B2?
riboflavin
A deficiency in Vitamin B2 causes what symptoms?
angular stomatitis, Cheilosis, corneal vascularization
What is the function of Vitamin B2?
Cofactor for oxidation and reduction (e.g., FADH2)
What is another name for Vitamin B3?
niacin
A deficiency in Vitamin B3 causes what symptoms?
Pellagra: diarrhea, dermatitis, dementia
What is the function of Vitamin B3?
Constituent of NAD, NADP (redox rxns); derived from tryptophan
What is another name for Vitamin B5?
pantothenate
A deficiency in Vitamin B5 causes what symptoms?
dermatitis, enteritis, alopecia, adrenal insufficiency
What is the function of Vitamin B5?
Constituent of CoA and component of FA synthase
What is another name for Vitamin B6?
pyridoxine
A deficiency in Vitamin B6 causes what symptoms?
convulsions, hyperirritability, peripheral neuropathy
What is the function of Vitamin B6?
converted to pyridoxal phosphate, a cofactor in transanimation, decarboxylation and heme synthesis
What is another name for Vitamin B12?
cobalamin
A deficiency in Vitamin B12 causes what symptoms?
macrocytic, megaloblastic anemia; neurologic symptoms; glossitis
What is the function of Vitamin B12?
cofactor in homocysteine methylation and methylmalonyl Co-A handlining
B12 is found in what types of foods?
Only animal products
What test is used to detect a B12 deficiency?
Schilling Test
What are the three main causes of a B12 deficiency?
Malabsorption, lack of intrinsic factor (pernicious anemia) or absence of terminal ileum (chron's dz)
A deficiency in folic acid causes what symptoms?
macrocytic megaloblastic anemia w/o neuro symptoms (unlike B12)
What is the function of Folic acid?
coenzyme for 1-carbon transfers (methylation rxns); needed for the synthesis of nitrogenous bases in DNA and RNA
Supplemental folic acid is given in pregnancy to prevent what defects?
neural tube
What is the folic acid precursor in bacteria?
PABA
A deficiency in biotin causes what symptoms?
dermatitis, enteritis
What is the function of biotin?
cofactor for carboxylation rxns: pyruvate -> oxaloacetate, Acetyl CoA -> malonyl CoA, Proprionyl CoA -> methylmalonyl CoA
What is another name for Vitamin C?
Ascorbic acid
A deficiency in Vitamin C causes what symptoms?
Scurvy - swollen gums, bruising, anemia, poor wound healing
What is the function of Vitamin C?
needed for the hydroxylation of proline and lysine in collagen synthesis; keeps Fe+2 in a reduced state increaseinf Fe absorption; cofactor for DA->NE
Vitamin C Cross-links collagen
A deficiency in Vitamin D causes what symptoms?
Rickets in children and osteomalacia in adults (improper bone mineralization); hypocalcemic tetany
What is the function of Vitamin D?
Increased absorption of Ca and P in the gut
What is the mechanism by which Vitamin D deficiency causes tetany?
less D -> less Ca -> lowering the membrane potential of a cell -> making it easier to get to threshold for AP
Excess of Vitamin D causes what symptoms?
Hypercalcemia, stupor, lossof appetite
A deficiency in Vitamin E causes what symptoms?
Increased fragility of erythrocytes, neurodysfunction
Vitamin E for Erythrocytes
What is the function of Vitamin E?
Antioxidant: protects erythrocytes from hemolysis
A deficiency in Vitamin K causes what symptoms?
Neonatal hemorrhage with increased PT and PTT, but normal bleeding time (neonates unable to synthesize Vit K)
K for Koagulation
What is the function of Vitamin K?
Catalyzes gamma-carboxylation of glutamic acid residues on various proteins concerned with clotting; synthesized by intestinal flora
What can cause a Vitamin K deficiency?
braod spectrum antibiotics (killing intestinal flora)
What are the Vitamin K dependent clotting factors?
II, VII, IX, X, protein C and S
Which drug is a Vitamin K antagonist?
Warfarin
A deficiency in zinc causes what symptoms?
delayed wound healing, hypogonadism, decreased adult hair
Outline the pathway of ethanol metabolism.
ethanol ->[alcohol dehydrogenase] -> Acetaldehyde ->[acetaldehyde dehydrogenase]-> acetate
What is the limiting reagent in the ethanol metabolism pathway?
NAD+
What are the pharmacokinetics of alcohol dehydrogenase?
zero-order
Which drug inhibits acetaldehyde dehydrogenase allowing for the accumulation of acetaldehyde and increasing hangover symptoms?
Disulfiram (anabuse)
Describe the mechainsm for ethanol hypoglycemia in chronic alcoholics.
Ethanol metabolism -> increased NADH/NAD+ ratio in liver -> pyruvate diverts to lactate and OAA diverts to malate -> inhibition of gluconeogenesis
Kwashiorkor is malnutrition resulting from what deficiency?
protein
What does a pt with Kwashiorkor look like?
small child with a swollen belly
Marasmus is a malnutrition syndrome resulting from what deficiency?
calories/energy
What does a pt with marasmus look like?
small child with tissue and muscle wasting
Describe the structure of chromatin.
(-)charged DNA loops choice around nucleosome core to form a nucleosome bead; H1 ties the nucleosomes together in a string
Beads on a string
Which is the only histone that is not in the nucleosome core?
H1
Which form of chromatin is transcriptionally inactive? Active?
Inactive: heterochromatin Active: Euchromatin
Need euchromatin to make You
Which amino acids are necessary for purine synthesis?
Glycine, Aspartate, Glutamine
Which nucleotide bonds are stronger and what is the consequence of this?
G-C bonds are stronger (3 H-bonds) resulting in a higher melting temperature
In regards to nucleotides, what is transition?
substitution of a purine for a purine or pyrimidine for pyrimidine
In regards to nucleotides, what is transversion?
substituting purine for pyrimidine or vice versa
What are the four main features of the genetic code?
unambiguous, degenerate, nonoverlapping, universal
What does it mean to say that the genetic code is degenerate?
more than one codon may code for the same amino acid
What is the mechanism of base excision repair?
Glycosylases remove damaged bases, endonuclease cuts DNA at apyrimidinic site, sugar is removed; gap is filled and resealed
What is the mechanism of mismatch repair?
unmethylated, newly synthesized string is recognized, mismatched nucleotides are removed; gap is filled and resealed
Which DNA repair mechanism is mutated in hereditary nonpolyposis colon cancer?
mismatch repair
What is the mechanism of nonhomologous end joining?
bringing together two ends of DNA fragments
What is the direction of DNA/RNA/protein synthesis?
5' -> 3'
How are amino acids joined?
N to C
What are the three types of RNA?
mRNA, tRNA, rRNA
Which type of RNA is the most abundant?
rRNA
Which type of RNA is the largest?
mRNA
Which type of RNA is the smallest?
tRNA
What is the function of RNA pol-I?
makes rRNA
remember that RNA pol-I, II, III are numbered as their products are used in protein synthesis
What is the function of RNA pol-II?
Makes mRNA
remember that RNA pol-I, II, III are numbered as their products are used in protein synthesis
What is the function of RNA pol-III?
makes tRNA
remember that RNA pol-I, II, III are numbered as their products are used in protein synthesis
What substance, found in death cap mushrooms, inhibits RNA pol-II?
a-amanitin
Which codon codes for methionine, thus initiating mRNA?
AUG
What are the three stop codons?
UAA, UAG, UGA
U Are Awful, U Are Gross, U Go Away
Which phase of the cell cycle is the shortest?
Mitosis
In which phase is new DNA synthesized?
S phase
S for synthesis
What type of cells remain in Go and are regenerated from stem cells?
Permanent cells such as neurons, skeletal and cardiac muscle, RBCs
What type of cells enter G1 from Go when stimulated?
Stable cells such as lymphocytes and hepatocytes
What type of cells never go to Go and divide rapidly with a short G1?
Labile cells such as bone marrow, gut epithelium, skin, and hair follicles
What is the function of the rough ER (RER)?
synthesis of secretory (exported) proteins and N-linked oligosaccharide addition to many proteins
What type of cells are rich in RER?
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells
What is the function of Nissl bodies in neurons?
synthesize enzymes (e.g., ChAT) and peptide neurotransmitters
What is the function of the smooth ER (SER)?
site of steroid synthesis and detoxification of drugs and poisons
What type of cells are rich in SER?
liver hepatocytes and steroid hormone-producing cells of the adrenal cortex
What are the 6 main functions of the Golgi apparatus?
taking protwins and lipids from the ER to the PM/lysosomes/secretory vesicles, 2. Modifies N-oligosac. On asparagine, 3. adds O-oligosac to Ser and Thr, 4. addd mannose-6P to lysosomal proteins (targeting to lysosome), 5. prtoeoglycan assembly, 6. sulfation of sugar on proteoglycans
What is the pathophys of I-cell disease and what are the consequences?
mannose-6P cannot be added to the lysosomal proteins so enzymes are secreted out of the cell instead of being targeted to the lysosome
What are the characteristics of I-cell disease?
coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes. Can be fatal in childhood
What are the three main cvesicular trafficking proteins and where do they go?
1. COP-I: retrograde, Golgi -> ER; 2. COP-II anterograde, RER -> cis-Golgi, 3.Clathrin: trans-Golgi->lysosomes, plasma membrane->endosomes (receptor mediated endocytosis)
In what cellular structures would one find microtubules?
flagella, cilia, mitotic spindles
What are the four main drugs that act on microtubules and for what dz?
1. Mebendazole/thiabendazole (antihelminthic), 2. Taxol (anti-breast ca), 3. Grisofulvin (antifungal), 4. Vineristine/vinblastine (anti-ca), 5. Colchicine (anti-gout)
What syndrome is caused by a defect in microtubule polymerization resulting in decreased phagocytosis?
Chediak-Higashi
Describe the structure of cilia.
9+2 arrangement of microtubules; doublets linked by dynein ATPase and allows for the bending of cilia
Which protein is responsible for retrograde motion of cilia? Anterograde?
retrograde = dynein, anterograde = kinesin
What is Kartagener's syndrome?
immobile cilia due to a dynein arm defect
What are the symptoms of Kartagener's syndrome?
infertility in both males and females, bronchiectasis, recurrent sinitus (any place where cilia are moving things around)
What are the two most abundant components of the plasma membrane?
cholesterol and phospholipids
What is the major component of RBC membranes, myelin, bile and surfactant?
phosphatidylcholine (lecithin)
What is the NA/ K exchange ratio in a Na/K ATPase pump?
3 Na out:2 K in
Explain when in the exchange is the Na/K ATPase pump phosphorylated/dephos?
Phosphorylated to let Na out (ATP->ADP) and dephosphorylated to let K in
What is the most abundant protein in the human body?
collagen
90% of all collagen is of what type?
Type I
Type I collagen provides support for which organs/functions?
Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair
Type I = bONE
Type II collagen provides support for which organs/functions?
Cartilage, vitreous body, nucleus pulposus
Type II = carTWOlage
Type III collagen provides support for which organs/functions?
Reticulin: skin, blood vessels, uterus, fetal tissue, granulation tissue
Type IV collagen provides support for which organs/functions?
Basement membrane or basa lamina
Type IV: under the FLOOR
What are the four phases of collagen synthesis in the fibroblasts and where do they take place?
1. synthesis (RER), 2. hydroxylation (ER), 3. glycosylation (Golgi), 4. exocytosis as procollagen
What are the two phases of collagen synthesis that occur outside of the fibroblasts?
1. proteolytic processing (procollagen ->tropocollagen), 2. cross-linking by covalent Lys-hydroxylysine = collagen fibrils
What stage of collagen synthesis requires Vitamin C?
hydroxylation in the ER
What are the three signs of Ehlers-Danlos syndrome?
1. hyperextensible skin, 2. tendency to bleed, 3. hypermobile joints (faulty collagen synthesis)
What type of collagen is most affected by Ehlers-Danlo syndrome?
Type III (blood vessel instability)
What is the most common form of osteogenesis imperfecta?
AD inheritance with abnl Type I synthesis
What are the key clinical features of osteogenesis imperfecta?
1. multiple fractures from minimal trauma (brittle bone), 2. blue sclerae (translucency of connective tissue over the choroid), 3. hearing loss, 4. dental imperfections
What may osteogenesis imperfecta be confused with upon examination?
child abuse
For the following cell type, state the immunohistochemical stain used to see it: connective tissue
Vimentin
For the following cell type, state the immunohistochemical stain used to see it: Muscle
Desmin
For the following cell type, state the immunohistochemical stain used to see it: Epithelial cells
cytokeratin
For the following cell type, state the immunohistochemical stain used to see it: Neuroglia
glial fibrillary acid proteins (GFAP)
For the following cell type, state the immunohistochemical stain used to see it: neurons
neurofilaments
In what structures does one find elastin?
lungs, large arteries, elastic ligaments
Elastin is rich in which two amino acids?
Proline and lysine
Marfan syndrome is caused by a defect in which component of elastin?
fibrillin
Elastase is inhibited in which disease? (Hint: it also causes early-onset emphysema)
a1-antitrypsin deficiency
What syndrome is caused by a defect in microtubule polymerization resulting in decreased phagocytosis?
Chediak-Higashi
Fructose intolerance is a hereditary deficiency of what enzyme?
Aldolase B
What is the pathophys of fructose intolerance?
fructose-1-P accumulates causing decreased available phosphate resulting in inhibition of glycogenolysis and gluconeogenesis
What is the tx for fructose intolerance?
decrease intake of both fructose and sucrose (glucose and fructose)
Essential fructosuria is a defect in which enzyme?
fructokinase
Galactosemia results from the absence in what enzyme?
galactose-1-phosphate uridyltransferase
What is the pattern of inheritance in galactosemia?
AR
What are the symptoms of galactosemia?
cataracts, hepatosplenomegaly, mental retardation
Lactase deficiency is a hereditary lactose intolerance due to a loss of what type of enzyme?
Brush border enzyme
What demographic is most susceptible to lactase deficiency and what are the sx?
blacks, Asians; bloating, cramps, osmotic diarrhea
What are the essential amino acids?
Phe, Val, Trp, Thr, Ile, Met, His, Arg, Leu, Lys
what is the pathophys of hyperammonemia?
excess NH4 depletes a-ketoglutarate, leading to inhibition of TCA cycle
What are the sx of ammonia intoxication?
tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring vision
What are the three main derivatives of phenylalanine?
Dopamine, NE, Epi
What are the three main derivatives of tryptophan?
Niacin, serotonin, melatonin
What causes the musty odor of PKU?
disorder of excess aromatic amino acids
Variable inheritance of albinism is due to what genetic mechanism?
locus heterozygosity
Albinism is a congential deficiency one of which two items?
1. Tyrosine (auto. Recess.) or 2. defective tyrosine transporters
All forms of homocystinuria have wha inheritance pattern?
autosomal recessive
What are the sx of homocystinuria?
mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis (stroke and MI)
The conversion of methionine to cysteine is dependent on which two vitamins?
B6 (homocysteine to cystothionine) and B12 (homocysteine back to Met)
Maple syrup urine disease is due to what defect?
Blocked degradation of branced amino acid (Ile, Val, Leu) due to decreased a-ketoacid dehydrogenase
What are the sx of maple syrup urine disease?
CNS defecs, mental retardation and death
Adenosine deanimase deficiency can cause what other major immunologic complication?
SCID
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Fabry's Dz
1. peripheral neuropathy of hands/feet, CV/renal dz
2. a-galactosidase A
3. ceramide trihexoside
4. XR
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Gaucher's Dz
1. hepatosplenomegally, aseptic necrosis of femur, bone crises, Gaucher cells (macrophages)
2. B-glucocerebrosidase
3. glucocerebroside
4. AR

Most common lysosomal storage dz
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Neimann-Pick
1. progressive neurodegeneration, hepatosplenomegally, cherry red spot (on macula)
2. Sphingomyelinase
3. Shingomyelin
4. AR
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Tay-Sachs
1. progressive neurodegeneration, developmental delay, lysozymes with onion skin
2. Hexosaminidase A
3. GM2 ganglioside
4. AR
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Krabbe's dz
1. peripheral neuropathy, developmental delay, optic atrophy
2. B-galactosidase
3. Galactocerebroside
4. AR
For the following lysosomal storage dz state (1) main findings, (2) deficient enzyme, (3)accumulated substrate and (4) inheritance pattern: Metachromic leukodystrophy
1. central and peripheral demyelination with ataxia and dementia
2. Arylsulfatase A
3. Cerebroside sulfate
4. AR
In fatty acid synthesis, the conversion of Acetyl-CoA to Malonyl CoA requires what cofactor?
Biotin
In fatty acid synthesis, what mechanism carries acetyl CoA across the inner mitochondril membrane into the cytoplasm?
Citrate shuttle
In fatty acid degradation, what mechanism carries acyl CoA across the inner mitochondrial membrane into the mitochondria?
carnitine shuttle
What is the rate limiting step in fatty acid degradation?
Carnitine shuttle
Under what physiological conditions will one see ketone bodies?
DKA or prolonged starvation
The rate limiting step in cholesterol synthesis is catalyzed by which enzyme?
HMG-CoA reductase
What is the classification of the drug Lovastatin?
HMG-CoA reductase inhibitor
What are the two essential fatty acids?
Linoeic acid and linolenic acid
What is the function of pancreatic lipase?
degradation of TG in sm intestine
What is the function of lipoprotein lipase?
degradation of TG circulating in chylomicrons and VLDLs
What is the function of Hepatic TG lipase?
degradation of TG remaining in IDL
What is the function of hormone-sensitive lipase?
Degradation of TG stored in adipocytes
What is the funtion of lecithin-cholesterol acyltransferase (LCAT)?
catalyzes the esterification of cholesterol
what is the function of cholesterol ester transfer protein (CETP)?
mediated the transfer of cholesterol esters to other lipoprotein particles
What is the role of apolipoprotein A-I?
activates LCAT
What is the role of apolipoprotein B-100?
binds to LDL receptor, mediates VLDL secretion
What is the role of apolipoprotein C-II?
cofactor for lipoprotein lipase
What is the role of apolipoprotein B-48?
mediates chylomicrom secretion
What is the role of apolipoprotein E?
Mediates remnant uptake (Extra uptake)
What is the function of the following lipoprotein: Chylomicron
delivers dietary TGs to peripheral tissues and cholesterol to the liver
What apo's are associated with chylomicrons?
B-48, A,C, and E
What is the function of the following lipoprotein: VLDL
delivers hepatic TGs to peripheral tissues
what apos are associated with VLDL?
B-100, C-II and E
What is the function of the following lipoprotein: IDL
Delivers TGs and cholesterol to the liver to be degraded to LDL
What apos are associated with IDL?
B-100 and E
What is the function of the following lipoprotein: LDL
delivers hepatic cholesterol to peripheral tissues
What apos are associated with LDL?
B-100
What is the function of the following lipoprotein: HDL
mediates centripital transport of cholesterol (periphery to liver); repository for apoC and apoE
Hypercholesterolemia has which Family type? what is increased?
Type IIa
Increased LDL
Combined hypercholesterolemia has which familial type? what is increased?
Type IIb
LDL, VLDL both increased
Hypertriglyceridemia has which familial type? what is increased?
Type IV
VLDL increased
Type IIa hypercholesterolemia has what pathophysiology?
decreased number of LDL receptors
What metabolic processes occur solely in the mitochondria?
FA oxidation (b-oxidation), acetyl CoA production, Krebs
What metabolic processes occur solely in the cytoplasm?
glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
What metabolic processes occur in both the mitochondria and the cytoplasm?
Gluconeogenesis, urea cycle, heme synthesis
Regeneration of methionine (and thus S-adenosyl-methionine/SAM) is dependent on what factor?
B12
What three enzymes are associated with respiratory burst in the phagolysosome?
NADPH oxidase
Superoxide dismutase
Myeloperoxidase
What three enzymes are associated with oxidative burst in the neutrophil?
Catalase/glutathione peroxidase
Glutathione reductase
G6PD
Fructose intolerance is an inherent deficiency of what enzyme?
aldolase B
What metabolic processes are inhibited from a fructose deficiency?
glyogenolysis and gluconeogenesis
What are the symptoms of fructose intolerance?
hypoglycemia, jaundice, cirrhosis, vomiting
What is the treatment for fructose intolerance?
decrease intake of fructose and sucrose (glucose and fructose)
the appearance of fructose in the blood or urine is due to a defect in what enzyme? What is the px?
fructokinase; the condition in benign and asymptomatic
Galactosemia is caused by the absence of what enzyme?
galactose-1-phosphate uridyltransferase
What is the inheritance pattern and sx of galactosemia?
AR; cataracts, hepatosplenomegally, mental retardation
Lactase deficiency is due to a loss of the enzyme from what area of the body?
Brush border
What are the symptoms of lactase deficiency?
bloating, cramps, osmotic diarrhea
Which are the essential amino acids?
Leu, Lys, Ile, Phe, Trp, Met, Thr, Val, Arg, His
Which two essential amino acids are increased in histones which bind negatively charged DNA?
Arg, Lys
What is the direct effect of excess NH4 (hyperammonemia) on metabolism?
depletes a-ketoglutarate -> inhibition of the TCA cycle
What is the treatment for hyperammonenmia?
Arginine
What are the signs of ammonia intoxication?
tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
What is the fnxn of the urea cycle?
to degrade amino acids into amino groups
What are the 8 main players in the urea cycle?
Ornithine, Carbamoyl, Citruline, Aspartate, Argininosuccinate, Fumarate, Arginine, Urea

Ordinarily Careless, Crappers Are Also Frivolous About Urination
What are the main derivatives of Phenylalanine?
Tyrosine
Dopamine
NE
EPI
What are the main derivatives of Tryptophan?
Niacin (NAD/NADP)
Serotonin
Melatonin
What are the main derivatives of Histidine?
Histamine
What are the main derivatives of Glycine?
Heme
What are the main derivatives of Arginine?
Creatine
Urea
NO
What are the main derivatives of glutamate?
GABA
What enzyme is decreased in PKU?
phenylalanine hydroxylase (or tetrahydrobiopterin cofactor)
What is the treatment for PKU?
Decrease phenylalanine and increase tyrosine
Alkaptonuria is caused by a deficiency of what enzyme?
homogentisic acid oxidase (alkapton bodies cause urine to turn black when standing)
Abinism is a congenital deficiency in what two factors?
Either tyrosinase or defective tyrosine transporters
Albinism exhibits variable inheritance due to what mechanism?
locus heterozygosity
What is the inheritance pattern for all three forms of homocystinuria?
AR
What are the three forms of homocystinuria?
1. cystathionine synthase deficiency
2. decreased affinity of cystathionine synthase for pyridoxal phosphate
3. methionine synthase deficiency
Cystinuria is a common inherited defect of...
the renal tubular amino acid transporter for cystine, ornithine, lysine, and arginine
What can be a sequellae of excess cystine in the urine?
cystine kidney stones
What is the treatment for cystinuria?
acetazolamide (alkalinize the urine)
Maple syrup urine disease is caused by a decrease in which enzyme?
a-ketoacid dehydrogenase
Which amino acids canno be degraded in maple syrup urine disease?
Ile, Leu, Val

I Love Vermont maple syrup
What is codominance?
Neither of two alleles is dominant (e.g. blood groups)
What is variable expression?
nature and severity of the phenotype varies from 1 individual to another
What is incomplete penetrance?
Not all individuals with a mutant genotype show the mutant phenotype
What is pleiotropy?
1 gene has > 1 effect on an individual's phenotype
What is imprinting?
At a single locus, only one allele is active; the other is inactive (methylation).Differneces in phenotype depend on whether the mutation is of maternal or paternal origin (e.g. Prader-Willi = paternal)
What is anticipation?
Severity of disease worsens or age of onset of disease is earlier in succeeding generations (e.g. Huntington's)
What is loss of heterozygosity?
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before the cancer develops (NOT true of oncogenes)
What is a dominant negative mutation?
exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
What is linkage disequilibrium?
tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in a population, not in a family, and often varies in different populations
What is mosacism?
when cells in the body have different genetic makeup (e.g.lyonization--random X inactivation in females)
What is locus heterogeneity?
Mutations at different loci can produce the same phenotype
If a population is in Hardy-weinberg equilibrium, how do you measure allele prevalence?
p^2 + 2pq + q^2 = 1, p and q are separate alleles and 2pq is the prevalence of heterozygotes
If a population is in Hardy-weinberg equilibrium, how do you measure allele prevalence?
p + q = 1
What are the 4 assumptions of Hardy-Weinberg law?
1. no mutation, 2. no selection for any of the genotypes at a locus, 3. Random mating, 4. no migration into or out of a population
In Prader-Willi, whose normally active allele is deleted (maternal or paternal)?
Paternal (opposite for angelman's)
What are some of the features of autosomal dominant inheritance?
many generations affected; both male and female; often pleiotropic; present after puberty
What are some of the features of autosomal recessive inheritance?
25% of offspring from 2 carrier parents affected; due to enzyme deficiencies; usually only seen in 1 generation; more severe than AD; presents in childhood
What are some of the features of X-linked recessive inheritance?
Sons of heterozygous mothers have a 50% chance; commonly more severe in males but heterozygous females may be affected
What are some of the features of X-linked dominant inheritance?
transmitted through both parents; ALL female offspring of an affected father will be diseased (either male of female from mother); hypophosphatemic rickets
What are some of the features of mitochondrial inheritance?
transmitted only through mother; all offspring of affected mother show disease; Leber's hereditary optic neuropathy
Mode of inheritance and major features: APKD
AD; always bilateral; mutation in APKD1 (Chr 16); berry aneurysms, mitral valve prolapse (juvie form is recessive)
Mode of inheritance and major features: familial hypercholesterolemia
AD; elevated LDL from a defective or absent LDL receptor; severe atherosclerosis disease at young age; tendon xanthomas (achilles); may have MI before age 20
Mode of inheritance and major features: Marfan's Syndrome
AD; fibrilin gene mutation = connective tissue disorders; tall; aortic incomptenece and dissecting aortic aneurysms; floppy mitral valve
Mode of inheritance and major features: Neurofibromatosis, type 1
AD long arm of chr. 17; café-au-lait spots; neural tumors; Lisch nodules (pigmented iris hamartomas); pheo's
Mode of inheritance and major features: Neurofibromatosis, type 2
AD; bilateral acoustic neuroma, juvenile cataracts; NF2 gene on chr 22 (type 2 = 22)
Mode of inheritance and major features: tuberous sclerosis
AD; facial lesions (adenoma sebaceum); hypopigmented "ash leaf spots" on skin; cardiac rhabdomyomas; incomplete penetrance/variable presentation
Mode of inheritance and major features: von Hippel-Lindau dz (VHL)
AD; hemangioblastomas of the retina/cerebellum/medulla; 50% develop multiple bilateral renal cell carcinomas; deletion of VHL gene on Chr 3 (three words for Chr 3)
Mode of inheritance and major features: Huntington's
AD; triplet repeat disorder on chr 4; depression; progressive dementia; choreiform movements; caudate atrophy; decreased levels of GABA and ACh in brain
Mode of inheritance and major features: Familial adenomatus polyposis
AD; progresses to colon cancer unless resected; Deletion on chr. 5 (5 letters in polyp)
Mode of inheritance and major features: Hereditary spherocytosis
AD; spheroid erythrocytes; hemolytic anemia; increases MCHC; splenectomy is curative
Mode of inheritance and major features: Achondroplasia
AD; cell-signalling defect of fibroblast growth factor (FGF) receptor 3; dwarfism (short limbs but head and truck are normal size); associated with advanced PATERNAL age
What gene is defective in cystic fibrosis?
CFTR on chromosome 7
What are the typical manifestations of a pt with CF?
recurrent pulmonary infections; infertility in males (absent vas deferens); fat soluble vitamin deficiencies
What is the treatment for CF?
n-acetylcysteine to loosen mucous plugs
What are the typical X-linked recessive disorders?
Bruton's agammaglobulinemia, Fragile X, G6PD deficiency, ocular albinism, Lesch-Nyhan, Duchenne's, Hemophilia A and B, Fabry's dz, Hunter's syndrome
Duchenne's MD is caused by what type of genetic mutation?
Frame shift leading to deletion of the dystrophin gene
What movement is a diagnostic sign of Duchenne's MD?
Gower's maneuver
What is the less severe form of duchenne's MD?
Becker's
What is the 2nd most common cause of genetic mental retardation after Down's?
Fragile X syndrome
What are the clinical features of Fragile X syndrome?
macro-orchidism, long face with a large jaw; large everted ears; autism
What type of disorder is Fragile X?
Triple repeat (CGG) - may show anticipation
What are the trinucleotide repeat diseass?
Huntington's, myotonic dystrophy, Friedreich's ataxia, Fragile X
What are the three autosomal trisomies and which chr's are affected?
Down's (21); Edward's (18); Patau (13)
What are the prenatal signs of Down's?
decreased a-fetoprotein, increased b-hCG, increased nuchal translucency
Pts with Down's are at risk of developing what neurological disorder?
early-onset Alzheimer's
95% of Down's cases are due to what problem in meiosis? What is the associated parental "problem"?
meiotic nondisjunction of homologous chromosomes; associated with advanced maternal age
Cri-du-chat is associated with what chromosomal abnormality?
congenital deletion of short arm of chr 5
22q11 syndromes are associted with what signs/symptoms?
cleft papate, abnormal facies, thymic aplasia (t-cell deficiency), cardiac defects, hypocalcemia 2' to parathyroid aplasia; variable presentation as DiGeorge
When are the risks for fetal alcohol syndrome the greatest?
3-8 weeks
What is the #1 cause of congenital malformations in the US?
Fetal Alcohol Syndrome