Usmle Step 1 -- Dit: Biochem

Front 1

To what main two molecules is iron bound in human cells? To what main two molecules is iron bound in blood?

Back 1

Myoglobin and ferritin; Hemoglobin and transferrin.

Front 2

What are some of the clinical effects of zinc deficiency?

Back 2

Delayed wound healing, acrodermatitis enteropathica, anorexia, diarrhea, growth retardation, depressed mental function, impaired night vision, and infertility.

Front 3

What are some of the signs of hypocalcemia?

Back 3

Tetany and neuromuscular instability, Chvostek's sign, Trousseau's sign.

Front 4

You see basophillic stippling on a peripheral blood smear. What's your diagnosis?

Back 4

Lead poisoning.

Front 5

What two enzymes are inhibited by lead poisoning?

Back 5

Ferrochelatase and ALA dehydratase.

Front 6

What might you see in an erythrocyte of a patient with lead poisoning?

Back 6

Basophillic stippling.

Front 7

What would be some of the clinical signs in a patient that would lead you to suspect lead poisoning?

Back 7

Anemia, colicky abd pain, diarrhea, nausea, encephalopathy, WRIST DROP, FOOT DROP, lead lines on gingivae

Front 8

What are the features of Plummer-Vinson syndrome?

Back 8

Dysphagia, glossitis, Iron-deficiency.

Front 9

What is the rate limiting step in the HMP shunt (PPP)? What is produced in this pathway? Which tissues utilize this pathway?

Back 9

G6PD; NADPH and Ribulose-5-P (for nucleotide synthesis); RBCs, liver, adrenal cortex, lactating mammary glands.

Front 10

A deficiency in G6PD leads to what? What is the inheritance pattern of this deficiency?

Back 10

Hemolytic anemia (no G6PD = no NADPH = no glutathione reductase activity = bunches of oxidized glutathione running around in the cell lysing stuff --> this is bad); X-linked.

Front 11

The respiratory burst (oxidative burst) is dependent on what enzyme?

Back 11

NADPH oxidase.

Front 12

What are the histological characteristics of G6PD deficiency?

Back 12

Heinz bodies and bite cells.

Front 13

What is the defective enzyme in essential fructosuria? What are the symptoms?

Back 13

FRUCTOKINASE -- i.e., fructose can't get into the cell; Asymptomatic -- fructose appears in blood and urine.

Front 14

What is the defective enzyme in Fructose Intolerance? What substrate accumulates? What are the symptoms?

Back 14

ALDOLASE B; Fructose-1-P accumulates in cell, bogarting all the phosphate! None for gluconeogenesis or glycogenolysis; Sx include hypoglycemia, jaundice, cirrhosis, vomiting.

Front 15

What are the symptoms of Galactokinase Deficiency?

Back 15

Accumulation of galactitol in the lens of eye --> can lead to infantile cataracts. Relatively benign condition.

Front 16

What is the deficient enzyme in Classic Galactosemia? How does it present?

Back 16

Galactose-1-phosphate uridyltransferase --> accumulation of toxic substances like galactitol; Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation, ascites.

Front 17

What enzyme converts glucose to sorbitol?

Back 17

Aldose reductase.

Front 18

What is the primary energy source in a patient that has not eaten in two days? What is the brain using for energy in this situation?

Back 18

Fatty acids. Glucose and some ketone bodies.

Front 19

What is the rate-limiting enzyme in ketone body synthesis?

Back 19

HMG-CoA synthase.

Front 20

Which ketone body is metabolized by muscle and brain tissue?

Back 20

β-hydroxybutarate.

Front 21

When does gluconeogenesis begin in the post-absorptive period? When does it become fully active?

Back 21

Begins 4-6 hours after the last meal; in full swing at 10-18 hours after last meal.

Front 22

What determines survival time after 3 days of starvation?

Back 22

Amount of adipose stores.

Front 23

This drug inhibits acetaldehyde dehydrogenase.

Back 23

Disulfuram -- acetaldehyde accumulates, contributing to hangover symptoms.

Front 24

This drug inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning.

Back 24

Fomepizole.

Front 25

How does chronic alcoholism cause hypoglycemia?

Back 25

The body needs NAD+ to metabolize alcohol, AND to do gluconeogenesis. The NAD+ gets depleted doing EtOH metabolism, increasing the NADPH:NAD+ and shutting down gluconeogenesis.

Front 26

What are some of the hallmarks of Kwashikor? How about Marasmus?

Back 26

Kwashikor: protein malnutrition, protruding belly, edema, skin lesions, sick liver, anemia.
Marasmus: generalized malnutrition, tissue and muscle wasting, loss of sc fat and variable edema.

Front 27

What deficiency causes familial hypercholesterolemia?

Back 27

Absent or decreased synthesis of LDL receptors.

Front 28

Which apolipoprotein is responsible for mediating the secretion of chylomicrons from the enterocytes of the gut?

Back 28

Apo B-48

Front 29

Which apolipoprotein binds to the LDL receptor and is also responsible for the secretion of VLDL from the liver?

Back 29

Apo B-100

Front 30

Which apolipoprotein acts as a cofactor for LPL?

Back 30

Apo C-II

Front 31

Which apolipoprotein mediates the uptake of chylomicron remnants?

Back 31

Apo E

Front 32

Which apolipoprotein activates LCAT?

Back 32

Apo A-1

Front 33

Where does FA synthesis take place? FA degradation? What are the rate-limiting enzymes for these reactions?

Back 33

Cytosol; Mitochondria; Acetyl Co-A carboxylase and Carnitine acyl transferase (CAT).

Front 34

Name 3 of the Omega-3 Fatty Acids.

Back 34

EPA, DHA, and α-Linoleic Acid.

Front 35

What are the essential amino acids?

Back 35

"PVT TIM HALL": Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histadine, Arginine, Leucine, and Lysine.

Front 36

What are the ketogenic amino acids?

Back 36

Leucine, Lysine.

Front 37

What are the glucogenic amino acids?

Back 37

Methionine, valine, arginine, histadine.

Front 38

What are the acidic amino acids?

Back 38

Aspartate and glutamate.

Front 39

What are the basic amino acids? Where do we find these guys?

Back 39

Arginine, Lysine, and histadine. You'll find these guys in the histones of DNA (b/c they are negatively charged)!

Front 40

What AA is the precursor to histamine?

Back 40

Histadine.

Front 41

What AA is the precursor to porphyrin and heme?

Back 41

Glycine.

Front 42

What AA is the precursor to NO?

Back 42

Arginine.

Front 43

What AA is the precursor to GABA?

Back 43

Glutamate.

Front 44

What AA is the precursor to SAM?

Back 44

Methionine.

Front 45

What is the AA precursor of creatine?

Back 45

Arginine.

Front 46

What is the path of catecholamine synthesis?

Back 46

Phenylalanine --> tyrosine --> dopa -> dopamine --> NE --> Epi

Front 47

A deficiency in tyrosine hydroxylase will lead to a build-up of what substrate?

Back 47

Tyrosine; can go to thyroxine.

Front 48

A deficiency in phenylalanine hydroxylase will lead to a build-up of what substrate?

Back 48

Phenylalanine.

Front 49

A deficiency in dopa carboxylase will lead to a build-up of what substrate?

Back 49

Dopa; can go to melanin.

Front 50

What are the catecholamine breakdown products via MAO and COMT?

Back 50

Dopamine --> HVA
NE --> VMA
Epi --> Metanephrine

Front 51

What is the rate limiting enzyme in the urea cycle? Where does this enzyme live?

Back 51

Carbamoyl phosphate synthetase I; it lives in the mitochondria.

Front 52

What is the most common urea cycle disorder? How does this present? What is the inheritance pattern?

Back 52

Ornithine transcarboamoylase (OTC) deficiency; Orotic acid in blood and urine (crystals in diaper), decreased BUN, sx of hyperammonemia; X-linked recessive.

Front 53

What are the symptoms of ammonia intoxication (hyperammonemia)?

Back 53

Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.

Front 54

Explain the mechanism of action of lactulose in removing NH4+ from the blood.

Back 54

Lactulose --> acidifies the gut --> traps NH4+ --> excretion.

Front 55

A full-term neonate becomes mentally retarded and hyperactive and has a must body odor. Phenylketones are detected in the urine. What is the diagnosis? What is the deficient enzyme?

Back 55

PKU. Deficient phenylalanine hydroxylase or tetrahydrobiopterin cofactor.

Front 56

What dietary modifications should a patient with PKU make?

Back 56

Decrease phenylalanine, increased tyrosine, increased THB.

Front 57

A middle-aged man has dark spots on his sclera and has noted that his urine turns black when left sitting for a period of time. What is the dx? What is the deficient enzyme?

Back 57

Alkaptonuria; Deficiency in homogentisic acid oxidase.

Front 58

Albinism is caused by a deficiency in one of these two things..

Back 58

Tyrosinase (which synthesizes melanin from tyrosine) or defective tyrosine transporters. Also can be d/t lack of migration of NEURAL CREST CELLS! remember, they give rise to melanocytes!

Front 59

What are the findings in a patient with homocystinuria?

Back 59

Elevated homocystine in urine, mental retardation, osteoporosis, tall stature, kyphosis, LENS SUBLUXATION and ATHERSCLEROSIS.

Front 60

What does S-adenosyl-methionine (SAM) do and what is required to regenerate SAM?

Back 60

Methyl donor -- required for the synthesis of epi from NE; Requires Vitamin B12 and folate in order to be regenerated.

Front 61

What causes Maple syrup urine disease?

Back 61

Blocked degradation of BRANCHED chain amino acids (isoleucine, leucine, and valine) due to deficient α-KETOACID DEHYDROGENASE.

Front 62

What symptoms does Hartnup disease present with?

Back 62

Tryptophan excretion in urine and decreased absorption from gut -- PELLAGRA.

Front 63

What accounts for the positive charge on histones? What accounts for the negative charge on DNA?

Back 63

Lysine and arginine residues; Phosphate groups.

Front 64

Which amino acids are required for de novo purine synthesis? What else is required?

Back 64

Glycine, aspartate, glutamine. THF.

Front 65

What is the rate-limiting enzyme in pyrimidine synthesis?

Back 65

CPSII. It happens in the cytosol, FYI.

Front 66

What is the biochemical result of Lesch-Nyhan syndrome?

Back 66

No HGPRT = no de novo synthesis of purines. Excess uric acid production and de novo purine synthesis. X-linked recessive.

Front 67

What is the main treatment for Lesch-Nyhan syndrome?

Back 67

Need to prevent excessive amounts of uric acid -- use a xanthine oxidase inhibitor like ALLOPURINOL.

Front 68

This drug blocks DHFR.

Back 68

Methotrexate (humans), TMP (bacteria).

Front 69

This drug block thymidylate synthase.

Back 69

5-FU.

Front 70

This drug blocks ribonucleotide reductase.

Back 70

Hydroxyurea.

Front 71

This drug blocks de novo purine synthesis.

Back 71

6-MP.

Front 72

What's the problem in orotic aciduria? What are the signs and sx?

Back 72

No conversion of orotic acid to UMP (de novo pyrimidine synth) d/t defect in orotic acid phosphoribyltransferase or orotidine 5-phosphate decarboxylase; increased orotic acid in urine (crystals in diaper), megaloblastic anemia refractive to B12 or folate tx, failure to thrive, no hyperammonemia.

Front 73

What is the defect in Xeroderma pigmentosum?

Back 73

Mutated nucleotide excision repair --> no repair of thymidine dimers caused by UV exposure.

Front 74

Which DNA repair mechanism is mutated in BRCA1 and BRCA2 mutations, and in patients with ataxia-telangiectasia?

Back 74

Nonhomologous end joining.

Front 75

What is the genetic defect responsible for HNPCC?

Back 75

Mismatch repair.

Front 76

What are the differences between carbamoyl phosphate synthetase I and II with regard to location, pathway, and nitrogen source?

Back 76

CPSI: Located in the mitochondria, urea cycle, and ammonia is its nitrogen source.
CPSII: Located in the cytosol, pyrimidine synthesis, glutamate is its nitrogen source.

Front 77

What are some of the sx of zinc deficiency?

Back 77

Delayed wound healing, decreased immune response, mental retardation, impaired vision, infertility, alopecia, dysgeusia, anosmia, ACRODERMATITIS ENTEROPATHICA (lesions around mouth and anus + diarrhea).

Front 78

To which molecules is iron bound in human cells? What about in the blood?

Back 78

Myoglobin and Ferritin; Transferrin and Hb.

Front 79

What are some of the signs of hypocalcemia?

Back 79

Trousseau's sign and facial spasm.

Front 80

What organs are primarily affected by cadmium excess?

Back 80

Bones, lung, kidney.

Front 81

What organs are primarily affected by an excess of mercury?

Back 81

Kidneys, brain.

Front 82

Which antibiotic inhibits prokaryotic RNA polymerase? Topoisomerase? DHFR?

Back 82

Rifampin; Fluoroquinolones; TMP.

Front 83

Which antibiotic inhibits 50S peptidyltransferase? Which binds 50S and blocks translocation? Which binds 30S and prevents attachment of tRNA?

Back 83

Streptogramins; Macrolides; Tetracyclines.

Front 84

How does Vit D exert its effects?

Back 84

Interacts directly with DNA to selectively stimulate or repress gene expression.

Front 85

What is another name for D2 and where does it come from? What is another name for D3 and where does it come from? How does Vit D deficiency manifest in children? adults?

Back 85

Ergocalciferol - plants.
Cholecalciferol - consumed in diet, synth in sun-exposed skin.
Rickets in children.
Osteomalacia in adults.

Front 86

How does Vit D def bring about Rickets and Osteomalacia?

Back 86

Decreased bone mineral deposition. If def occurs at the growth plate, growth slows and bone age is retarded (Rickets). Poor mineralisation of trabecular bone, resulting in a greater proportion of unmineralised osteoid, is the condition of osteomalacia. Rickets is found only in growing children before fusion of the epiphyses, whereas osteomalacia is present at all ages.

Front 87

What enzyme is responsible for the activation of Vit D? Where does this process occur?

Back 87

α1-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the KIDNEY.

Front 88

In what disease does Vit D toxicity result from excess MACROPHAGE generation of 25-hydroxycholecalciferol?

Back 88

Sarcoidosis.

Front 89

What pharmacological agents can cause Vit K deficiency with long-term use?

Back 89

Warfarin, antibiotics (loss of gut bacteria), anticonvulsants.

Front 90

What are the different forms of Vitamin A?

Back 90

Retinol, retinal, B-carotene, retinoic acid.

Front 91

What disease can be treated with Vitamin A?

Back 91

AML-M3, measles.

Front 92

What is the function of Vitamin A?

Back 92

Antioxidant, constituent of visual pigment, need it for normal differentiation of epithelial cells.

Front 93

What are the signs of Vitamin A deficiency?

Back 93

Lots of EYE PATHOLOGY: Night blindness, xeropthalmia, corneal ulceration, keratmalacia (clouding of cornea), Bitot's spots (silver plaques on the conjunctiva).

Front 94

What are the signs of hypervitaminosis A?

Back 94

Headache, N & V, stupor, dry + pruritic skin, hepatomegaly, bone and joint pain, alopecia, increased ICP; TERATOGEN in pregnant women (NC defects -- cleft palate, cardiac abnormalities, etc.).

Front 95

What headache condition can most commonly result from an excess of Vitamin A?

Back 95

Pseudotumor cerebri.

Front 96

What is the main metabolic reaction that Vitamin C is involved in?

Back 96

Hydroxylation of proline and lysine residues in the synthesis of collagen.

Front 97

What are the major signs of Vit C deficiency?

Back 97

Sore, spongy gums, loose teeth, fragile blood vessels --> hemorrhages, swollen joints (bleeding into joint spaces), impaired wound healing, anemia.

Front 98

What is the primary function of Vitamin E?

Back 98

Antioxidant -- protects RBCs from non-enzymatic oxidation of cell components.

Front 99

What is associated with Vitamin E deficiency? What autosomal recessive gene mutation is responsible for Vitamin E deficiency?

Back 99

Spinocerebellar degeneration leading to ATAXIA, peripheral neuropathy, proximal muscle weakness, increased fragility of RBCs, ACCELERATED ATHEROSCLEROSIS; α-tocopherol transfer gene protein.

Front 100

What is the biologically active form of folic acid? What metabolic reactions is it involved in? What does a deficiency in folic acid cause?

Back 100

THF; synthesis of purines (A, G) and thymine (T); megaloblastic anemia, growth defects, neural tube defects.

Front 101

What results from an excess of folate? Why?

Back 101

Vitamin B12 deficiency, it's used in making THF -- get this, A deficiency in B12 can cause a deficiency in folate.

Front 102

In what metabolic reactions in Vitamin B12 involved?

Back 102

Homocysteine and THF-CH3 --> Methionine and THF.
Methylmalonyl CoA --> Succinyl CoA.

Front 103

What is seen in B12 deficiency?

Back 103

Pernicious anemia; megaloblastic anemia, CNS sx, atrophy of stomach glands, homocysteinuria and methylmalonic acid in urine.

Front 104

What is another name of B12 deficiency?

Back 104

Subacute combined degeneration.

Front 105

What is usually the cause of B12 malabsorption? Where is B12 absorbed in the GI tract? Name two malabsorption problems that can cause B12 deficiency.

Back 105

AI destruction of parietal cells = no IF = no B12 absorption; terminal ileum; Crohn's disease and celiac sprue.

Front 106

What is the tx for B12 deficiency?

Back 106

IM injection of cyanocobalamin.

Front 107

What is the biologically active form of Vitamin B6? What is its metabolic function?

Back 107

Pyridoxal phosphate; coenzyme for many enzymes, esp those involved in AA metabolism (transamination).

Front 108

What drugs can cause a B6 deficiency? What are the clinical findings of a B6 deficiency?

Back 108

Isoniazid, OCPs; Convulsions, hyperirritability, and peripheral neuropathy.

Front 109

What is Vitamin B1? What reactions is Vitamin B1 involved in?

Back 109

Thiamine; pyruvate --> acetyl CoA (via PDH); α-Ketoglutarate --> succinyl CoA for TCA cycle (via α-Ketoglutarate dehydrogenase; Ribose 5-P --> G3P in HMP shunt (via transketolase).

Front 110

What two syndromes are associated with B1 deficiency? In which populations do these occur?

Back 110

Beriberi (dry and wet) -- populations where rice is the major component of the diet; Wernicke-Korsakoff syndrome -- alcoholics.

Front 111

What are the characteristics of dry beriberi? Wet beriberi?

Back 111

Peripheral neuropathy, toe-drop, wrist-drop, and foot-drop, muscle weakness, hyporeflexia and areflexia; Wet beriber includes peripheral vasodilation --> high-output heart failure --> peripheral edema, cardiomegaly.

Front 112

Describe Wernike-Korsakoff syndrome. What is the classic triad? What are other sx?

Back 112

Classic Triad : Confusion, opthalmoplegia, ataxia; other sx include confabulation, personality change, memory loss (permanent).

Front 113

What are the two biologically active forms of B2 (riboflavin)? What is their function?

Back 113

FMN and FAD, cofactors in oxidation and reduction reactions.

Front 114

What are some of the symptoms of B2 deficiency? In what populations is this prevalent?

Back 114

Dermatitis, cheilosis/angular stomatitis (fissuring and inflammation at the corners of the mouth), glossitis, corneal vascularization; denture wearers.

Front 115

What are the biologically active forms of niacin (Vitamin B3)? What is their function?

Back 115

NAD+, NADP+; cofactors for oxidation-reduction reactions.

Front 116

From which amino acid is niacin derived?

Back 116

Tryptophan.

Front 117

What disease is caused by niacin deficiency? What are the sx? What can cause niacin deficiency?

Back 117

Pellagra; diarrhea, dementia, dermatitis; Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), INH (decreased Vit B6).

Front 118

What is the function of Vit B5 (pantothenate)? What sx occur with deficiency?

Back 118

It's a component of coenzyme A and fatty acid synthase; "DEA": dermatitis, enteritis, alopecia, adrenal insufficiency.

Front 119

What is the metabolic role of biotin? What can cause a deficiency in biotin?

Back 119

Apoenzyme in carboxylation reactions; excessive consumption of egg whites, abx use. (gut bacteria make biotin for us).