Usmle Biochem

Front 1

Fabry's Disease

Back 1

Sx - peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease

deficient a-galactosidase A
accum: ceramide trihexoside

X-linked recessive

Front 2

Gaucher's Disease

Back 2

Sx - hepatosplenomegaly, asceptic necrosis of femur, bone crisis, Gaucher's cells (mac's crumpled like tissue paper)

deficient b-glucocerebrosidase
accum: glucocerebroside

autosomal recessive

Front 3

Niemann-Pick

Back 3

Sx - neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells

deficient sphingomyelinase
accum - sphingomyelin

autsosomal recessive

Front 4

Tay-Sachs Disease

Back 4

progressive neurodegeneration, developmental delay, cherry-red spot, lysosomes w/ onion skin

Hexosamindase A deficiency
GM2 ganglioside accumulates

autosomal recessive

Front 5

Krabbe's Disease

Back 5

peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Galactocerebrosidase deficiency
Galactocerebroside accumulates

Front 6

Metachromatic leukodystrophy

Back 6

Central and peripheral demyelination with ataxia, dementia

Arylsulfatase A deficiency
Cerebroside sulfate accum

autosomal recessive

Front 7

Hurler's syndrome

Back 7

developmental delay, gargoylism, airway obstruction, corneal clouding

a-L-iduronidase deficient
heparan sulfate, dermatan sulfate accumulates

autosomal recessive

Front 8

Hunter's syndrome

Back 8

Mild hurler's + aggressive behavior, no corneal clouding

iduronate sulfate deficient
heparan sulfate, dermatan sulfate accumulate

x-linked recessive

Front 9

Adult polycystic kidney disease

Back 9

Always bilateral, massive enlargement of kidneys due to multiple large cysts. Presents w/ pain, hematuria, HTN, progressive renal failure. 90% of cases due to mutation in APKD1 on chr 16. Associated w/ polycystic liver disease, berry aneurysms, mitral valve prolapse. Juvenile form in recessive.

Front 10

Familial hypercholesterolemia
hyperlipidemia type IIA

Back 10

Elevated LDL owing to defective or absent LDL receptor. Heterozygotes have cholesterol ~300, homozygotes (rare) have cholesterol 700+, severe atherosclerotic disease early in life, tendon xanthomas esp in Achilles tendon, MI before age 20.

Front 11

Marfan's syndrome

Back 11

Fibrillin (sheath of elastin) gene mutation causing connective tissue disorders.
Skeletal abnormalities - tall with long extremities, pectum excavatum, hyperextensive joints, long, tapering fingers and toes - arachnodactyly
Cardiovascular - cystic medial necrosis of aorta, leading to aortic incompetence and dissectin aortic aneurysms. Floppy mitral valve.
Ocular - subluxation of lenses

Front 12

Neurofibromatosis type 1
von Recklinghausen's disease

Back 12

Findings - cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (scoliosis), optic pathway gliomas, pheochromocytomas, increased tumor susceptibility. on chr 17

Front 13

Neurofibromatosis type 2

Back 13

Bilateral acoustic neuromas, jeuvenile cataracts, NF2 gene on chr 22

Front 14

Tuberous sclerosis

Back 14

facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas. incomplete penetrance, variable presentation.

Front 15

von Hippel-Lindau disease

Back 15

hemangioblastomas of retina/cerebellum/medulla. about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors. Assoc w/ deletion of VHL gene (tumor suppressor) on chr 3, von Hippel Lindau - three words for chr 3

Front 16

Huntington's disease

Back 16

Depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of GABA and ACh in the brain. Sx manifest in affected individuals b/n ages of 20-50. Located on chr 4; triplet repeat disorder.

Front 17

Familial adenomatous polyposis

Back 17

colon covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected. Deletion on chromosome 5 APC gene.

Front 18

Hereditary spherocytosis

Back 18

Spheroid erythrocytes; hemolytic anemia. increased MCHC. Splenectomy is curative.

Front 19

Achondroplasia

Back 19

Autosomal-dominant cell-signaling defect of fibroblast growth factor FGF receptor 3. Results in dwarfism; short limbs but head and trunk are normal size. Assoc w/ advanced paternal age.

Front 20

Vitamin A

Back 20

Deficiency - night blindness, dry skin

Function - constituent of visual pigments in retina. Found in leafy vegetables.

Excess - Arthralgias, fatigue, headaches, skin changes, sore throat, alopecia.

Front 21

Vitamin B1

Back 21

Thiamine

Deficiency - Beriberi (Dry - polyneuritis, symmetrical muscle wasting; wet - high-output cardiac failure, dilated cardiomyopathy, edema) and
Wernicke-Korsakoff syndrome (confusion, ataxia, opthalmoplegia, hemorrhage and necrosis of mamillary bodies)

Functions in thiamine pyrophosphate, a cofactor fo oxidative decarboxylation of a-ketoacids and branched chain AA dehydrogenase, and a cofactor for transketolase in HMP shunt.

Front 22

Vitamin B2

Back 22

Riboflavin

Deficiency - Angular stomatitis (inflammation of oral mucous linings), Cheilosis (inflam of lips), Corneal vascularization

Function - cofactor in oxidation and reduction, FAD and FMN - make 2 ATP

Front 23

Vitamin B3

Back 23

Niacin.

Deficiency - made from body tryptophan, synthesis requires B6. Pellagra can be caused by Hartnup's disease (dec tryptophan absorption), malignant carcinoid syndrome (inc tryptophan metabolism), INH (dec B6)

Pellagra = 3D's : Diarrhea, Dermatitis, Dementia (beefy glossitis)

Constituent of NAD, NADP in redox rxns

Front 24

Vitamin B5

Back 24

Panthogenate = part of CoA

Deficiency - dermatitis, enteritis, alopecia, adrenal insufficiency

Function - constituent of CoA and component of fatty acid synthase

Front 25

Vitamin B6

Back 25

Pyridoxine.

Deficiency - Convulsion, hyperirritability, peripheral neuropathy. deficiency inducible by INH and COC's)

Function - converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation rxns, glycogen phosphorylase, heme synthesis. Required for synthesis of niacin from tryptophan

Front 26

Vitamin B12

Back 26

Cobalamin.

Deficiency - macrocytic, megaloblastic anemia, neurologic symptoms ( optic neuropathy, subacute combined degeneration, paresthesia), glossitis.

Function - Cofactor for homocystein methyltransferase, transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase.
Stored primarily in the liver, very large reserve pool (several years). synthesized by microorganisms. In animal products.

Causes - malabsorption, lack of intrinsic factor, absence of terminal ileum.

Front 27

Folic Acid

Back 27

Most common vitamin deficiency in US

Deficiency - macrocytic, megaloblastic anemia w/ no neurologic symptoms.

Function - Coenzyme for 1-carbon transfer; involved in methylation rxns, synthesis of nitrogenous bases. found in green leaves.

Front 28

Biotin

Back 28

Deficiency - dermatitis, enteritis. Rare, caused by antibiotic sues, excessive ingestion of raw eggs.

Cofactor for carboxylations
pyruvate to oxaloacetate
Acetyl-CoA to malonyl CoA
Propionyl-CoA to methylmalonyl-CoA

Front 29

Vitamin C

Back 29

Scurvy - swollen gums, bruising, anemia, poor wound healing, petechiate

Necessary for hydroxylation of proline and lysine in collagen synthesis.
Facilitations iron absorption by keeping in Fe2+ state
Necessary as a cofactor for dopamine beta-hydroxylase, converts dopamine to NE

Front 30

Vitamin D

Back 30

ergocalciferol form in milk
cholecalciferol formed in skin

Deficiency - rickets in children, osteomalacia in adults, hypocalcemic tetany.

Function - inc intestinal absorption of calcium and phosphate.

Excess - hypercalcemia, loss of appetite, stupor. seen in sarcoidosis, disease where epithelioid mac's convert vit D to active form

Front 31

Vitamin E

Back 31

Deficiency - increased fragility of erythrocytes, neurodysfunction.

Function - antioxidant

Front 32

Vitamin K

Back 32

Deficiency - Neontatl hemorrhage w/ elevated PT and PTT, but normal bleeding time.

Function - catalyzes carboxylation of glutamic acid residues on various proteins concerned with blood clotting - factors II, VII, IX, X and proteins C and S. synthesized by intestinal flora - absent at birth and after antibiotic use.

Front 33

Zinc deficiency

Back 33

Delayed wound healing, hypogonadism, decreased adult hair in axilla, facial, pubic, may predispsoe to alcoholic cirrhosis.

Front 34

Amino acids needed for purine synthesis

Back 34

Glycine
Aspartate
Glutamate

In the De novo pathway, purines are made from IMP precursor

Front 35

Transition vs. Transversion

Back 35

Transition - substituting purine for purine or pyrimidine for pyrimidine

Transversion - substituting purine for pyrimidine or vice versa

Front 36

DNA polymerase III

Back 36

Elongates the chain by adding deoxynucleotides to the 3' end (leading strand).

Elongates lagging strand until it reaches primer of preceding fragment.

3' --> 5' exonuclease activity proofreads each added nucleotide.

Front 37

DNA polymerase I

Back 37

Degrades RNA primer (5' --> 3' exonuclease) and fills in the gap with DNA

Front 38

Stop codons

Back 38

UGA
UAA
UAG

Front 39

Cell Cycle regulators

Back 39

CDK - constitutive and inactive

Cyclins - phase specific, activate CDKs

Rb and p53 tumor suppressors normally inhibit G1 to S progression.

Front 40

I cell disease

Back 40

Failure of addition of mannose-6-phosphate lysosome proteins.
Enzymes are secreted outside the cell instead of being targeted to the lysosome.

Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes.

Often fatal in childhood

Front 41

Chediak-Higashi syndrome

Back 41

due to a microtubule polymerization defect resulting in decreased phagocytosis, can't fuse lysosomes.

Increased susceptibility to infection, esp S. aureus, due to defects in chemotaxis, degranulation and bacteriocidal activity

Front 42

Kartagner's syndrome

Back 42

Immotile cilia due to a dynein arm defect.

Results in male and female infertility, bronchiectasis, recurrent sinusitis.

Associated w/ situs inversus

Front 43

Osteogenesis imperfecta

Back 43

Variety of gene defects; all result in abnormal collagen synthesis.

Most common form is autosomal-dominant with abnormal collagen type I.

1. multiple fractures occuring with minimal trauma, during birth
2. Blue sclerae - translucency of connective tissue over the choroid
3. Hearing loss - abnormal middle ear bones
4. Dental imperfections - lack dentin

Front 44

Metabolic processes in the mitochondria

Back 44

Fatty acid oxidation (beta)
acetyl-CoA production
Krebs cycle
oxidative phosphorylation

Front 45

Metabolic processes in the cytoplasm

Back 45

Glycolysis
fatty acid synthesis
HMP shunt
Protein synthesis RER
Steroid synthesis SER

Front 46

Hexokinase vs. Glucokinase

Back 46

Hexokinase -
high affinity (low Km), low capacity (low Vmax), uninduced by insulin

Glucokinase -
low affinity (high Km) and high capacity (high Vmax), induced by insulin, only in liver and pancrease

Front 47

Coenzymes required by pyruvate dehydrogenase complex

Back 47

1. Pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenate)
5. Lipoic acid

Arsenic inhibits lipoic acid and results in vomiting, rice water stools, garlic breath.

Front 48

Alkaptonuria

Back 48

Deficient homogentiasate oxidase

Accumulate homogentisate

Black urine and cartilage, degenerative arthritis

Front 49

Galactosemia

Back 49

Galactose 1-phosphate uridyltransferase deficiency

accumulate galactose 1-phosphate

Mental retardation, cirrhosis, hypoglycemia.cataracts (galactitol)
Avoid dairy products

Front 50

Hereditary fructose intolerance

Back 50

deficient Aldolase B

accumulate fructose 1-phosphate

Cirrhosis, hypoglycemia, renal disease

Avoid fructose, sucrose, honey

Front 51

Homocystinuria

Back 51

deficient Cystathionine synthase

accumulate homocystein and methionine

Mental retardation, vessel thrombosis

Front 52

Maple syrup urine disease

Back 52

Branched chain alpha-ketoacid dehydrogenase deficient

Accumulate leucine, valine, isoleucine and their ketoacids.

Mental retardation, seizures, feeding problems, sweet smelling urine

Front 53

McArdles' disease
type V glycogen storage disease

Back 53

Deficient muscle phosphorylase

Accumulate glycogen

Glycogenosis, muscle fatigue, myoglobinuria, painful cramps, no increase in lactic acid w/ exercise

Front 54

Phenylketonuria

Back 54

Deficient Phylalanine hydroxylase

Accumulate phenylalanine

Mental retardation, microcephaly, decreased tyrosine (essential), fair skin, eczema, musty body odor (aromatic amino acids)

Restrict phenylalanine, avoid artificial sweetners containing phenylalanine

Autosomal recessive

Front 55

Pompe's disease
type II glycogen storage disease

Back 55

Deficient alpha-1,4 glucosidase lysosomal enzyme

Accumulate glycogen

Glycogenosis, cardiomegaly with early death

Front 56

Von Gierke's disease

Back 56

Deficient Glucose-6-phosphatase (gluconeogenic enzyme)

Accumulate glucose-6-phosphate

Glycogenosis, enlarged liver and kidneys, hypoglycemia, elevated lactate
no increase in glucose w/ glucagon challenge.

Front 57

Fragile X

Back 57

Trinucleotide repeat disorder of FMR1 gene
associated w/ chromosome breakage

X-linked recessive.

Mental retardation, autism.
Long face, large mandible, everted ears.
Macro-orchidism

Front 58

Lesch-Nyhan Syndrome

Back 58

Deficiency of hypoxanthine-guanine phosphoribosyltranfserase

Involved in slavaging the purines hypoxanthine and guanine

Excess uric acid production

Mental retardation, Hyperuricemia, self-mutilation, aggression, gout, choreoathetosis

X-linked recessive

Front 59

Down's syndrome

Back 59

Trisomy 21

Mental retardation
Epicanthic folds, flat facial profile, macroglossia
Simian crease

Risk of Hirschsprung's disease and duodenal atresia, increased risk of leukemia, Alzheimers

dec AFP, inc hCG, dec urine estriol

Front 60

Edward's syndrome

Back 60

Trisomy 18

Metal retardation.
Clenched hands with overlapping fingers
VSD
Rocker-bottom feet
Early death

Front 61

Patau's syndrome

Back 61

Trisomy 13

Mental retardation, cleft lip and palate
Polydactyl, VSD, cystic kidneys, rocker-bottom feet
Early death

Front 62

Cori cycle

Back 62

Allows lactate generated during anaerobic metabolism to undergo hepatic gluconeogenesis and become a source of glucose for muscle/RBC.

Comes at the cost of a net loss of 4 ATP/cycle

Front 63

Irreversible enzymes of Gluconeogenesis

Back 63

Pyruvate carboxylase - in mitochondria, converts pyruvate to oxaloacetate

PEP carboxykinase - in cytosol, converts oxaloacetate to PEP

Fructose 1,6 bisphosphatase - in cytosol. Fructose1,6P to F6P

Glucose 6 phosphatase - in ER, G6P --> glucose

only in liver, kidney, intestine

only odd chain fatty acids can enter TCA cycle and gluconeogenesis via propionyl-CoA

Front 64

Essential fructosuria

Back 64

defect in fructokinase
benign, asymptomatic
fructose in blood and urine
fructose does not enter cells

Front 65

Hyperammonemia

Back 65

Aquired with liver disease or hereditary, for example w/ ornithine transcarbamoylase deficiency

Excess NH4 depletes a-ketoglutarate, leading to inhibition of TCA cycle

Ammonia intoxication - tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Rx - benzoate or phenylbutyrate to lower serum ammonia

Front 66

Albinism

Back 66

Defects in either
1. Tyrosinase - inability to synthesize melanin from tyrosine - autosomal recessive
2. Defective tyrosine transporters - dec amounts of tyrosine, so dec melanin

Can also result for lack of migration of neural crest cells.
Inc risk of skin cancer.

Variable inheritance due to locus heterogeneity

Front 67

Homocysteinuria

Back 67

Three forms, all autosomal recessive

1. Cystathionine synthase deficiency
Rx - Dec Met, Inc Cys, Inc B12 in diet

2. Decreased affinity of cystathionine synthase for pyridoxal phosphate
Rx - Inc B6 in diet

3. Homocystein methyltransferase deficiency

All forms result in excess homocystein and cysteine becomes essential.

Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI).

Front 68

Cysteinuria

Back 68

Common inherited defect of renal tubular amino acid transportor for cysteine, ornithine, lysine and arginin in PCT of kidneys

Excess cystine in urine can lead to ppt of cystine kidney stones (staghorn calculi)

Rx - acetazolamide to alkalinize urine

Front 69

Maple syrup urine disease

Back 69

Blocked degradation of branched amino acids Ile, Val, Leu due to dec alpha-ketoacid dehydrogenase.

Inc alpha-ketoacids in the blood, esp Leu

CNS, defects, mental retardation, death, Urine smells like maple syrup

Front 70

What are the functions of apolipoproteins AI, B100, CII, B48, E?

Back 70

AI - activates LCAT (esterifies cholesterol)

B100- binds to LDL receptor, mediates VLDL secretion

CII - Cofactor for lipoprotein lipase

B48 - Mediates chylomicron secretion

E - mediates extra remnant uptake

Front 71

Hyperchylomicronmeia

Back 71

Type 1 familial dyslipidemia

Increased chylomicrons

Elevated TG, cholesterol

LPL deficiency or altered CII

Pancreatitis, lipema retinalis, eruptive xanthomas

Front 72

Hypercholesterolemia

Back 72

Type IIa familial dyslipidemias

Inc LDL

Elevated cholesterol

Decreased LDL receptors

Front 73

Hypertriglyceridemia

Back 73

Type IV dyslipidemia

Inc VLDL

Elevated TG

Hepatic overproduction of VLDL

Front 74

Acute intermittent Porphyria

Back 74

Deficient prophobilinogen deaminase

Accumulate porphobilinogen and delta-ALA

Abd pain, neurologic manifestations, urine darkens when standing

No photosensitivity

Front 75

Porphyria cutanea tarda

Back 75

Deficient uroporphyrinogen decarboxylase

Accumulate uroporphyrin (tea-colored)

Abd pain, pink urine, polyneuropathy, psychologica disturbances, precipitated by drugs.
Photosensitive

Front 76

Lead poisoning

Back 76

Defective Ferrochelatase and ALA dehydratase

Accumulate coproporphyrin and delta-ALA

Front 77

Factors that cause the Hb O2 dissociation curve to shift to the right

Back 77

Increases Cl, H+, CO2, 2,3BPG and temperature

Cause increased unloading

Front 78

Prader Willi

Back 78

Deletion of normally active paternal allele

Mental retardation, obesity, hypogonadism, hypotonia

Front 79

Angleman's syndrome

Back 79

Deletion of normally active maternal allele

MR, seizures, ataxia, inappropriate laughter (happy puppet)

Front 80

Cri-du-chat Syndrome

Back 80

congenital deletion of short arm of chromosome 5

microcephaly, severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities

Front 81

22q11 syndromes

Back 81

Cleft palate, Abnormal facies, Thymic aplasia (T cell deficiency), Cardiac defects, Hypocalcemia (parathyroid aplasia)

Microdeletion at 22q11

Variable presentation as DiGeorge's (thymic, parathyroid, cardiac) or velocardiofacial (palate, facial, cardiac)