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USMLE Step 1 Biochemistry

Subjects : health-sciences, usmle-step-1

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Answer 50 questions in 15 minutes.
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1. How do you differentiate causes of megaloblastic anemia?
Citrate - Isocitrate - alpha ketoglutarate - Succinyl CoA - Succinate - Fumarate - Malate - Oxaloacetate
Orotic aciduria megaloblastic anemia can not be corrected with folic acid or vit B12
Peripheral neuropathy - developmental delay - optic atrophy - globoid cells
Cells that stay in G0 and cannot replicate - instead they regenerate from stem cells; neurons - skeletal and cardiac muscles - and RBCs

2. From What aa does porphyrin come from? What is porphyrin the precursor of?
Depression - progressive dementia - choreiform movements; between the ages of 20 and 50
Neural tissue and adrenal medulla
Glycine; heme
Acetyl coA carboxylase converting Acetyl coA into malonyl coA; increased AMP - glucagon - epinephrine - palmitate; citrate

3. The three steps of PCR
Zero order; increased production of NADH no matter the amount of end products produced
Marfans and emphysema; marfans is a fibrillin protein defect - fibrillin is a supporting protein in tropoelastin scaffolding and results in aorta - skeletal and eye defects; emphysema is due to a deficiency in the function of alpha 1 antitrypsin
1. denature by heating 2. during cooling anneal with DNA primers 3. elongation - add heat stable DNA polymerase 4. repeat
Malabsorption problems (CF and sprue) and mineral oil intake

4. What is the result of lactase deficiency? in What nationalities is it seen the most?
Branched chain alpha keto acid dehydrogenase; inability to break down branched chain aa
Lack of lactase (brush border enzyme) so can not break down lactose (a dissaccharide of galactose and glucose); African Americans and Asians
It contains the peptidyltransferase activity (for elongation of protein
Increased G3P for TG synthesis - increased acetyl CoA (Fatty acid synthesis for TG synthesis) - and decreased oxidation of FA in the mitochondria due to alcohols toxicity on the mit

5. After the PCR reaction - How do you actually visualize the DNA?
Do agarose gel eletrophoresis to separate the different sizes of the PCR products (sizes id the the fragment)
Pernicious anemia; older - mentally slow european woman who is anemic and icteric with a smooth shiny tongue and has broad based shuffling gait
P53 and Rb; p53 activates BAX Which inhibits BCL2 When there is DNA damage - Rb phosphorylation allows progression into S phase
30S + 50S= 70S

6. What are the symptoms of williams syndrome? What is the pathogenesis?
An aminotransferase enzyme transfers an amino group from an amino acid on to alpha ketoglutarate making it a glutamate (to join the urea cycle or excreted in the kidney) and the amino acid that lost the amino group is then turned into a glycolytic in
only L form
Cortisol; inhibits insulin action
Distinctive elfin faces - mental retardation - hypercalcemia d/t sensitivity to vit D - well developed verbal skills and extreme friendliness - CV problems

7. What creates a frameshift mutation? What are some clinical examples?
Tyrosine
glutton
Insertion or deletion of a number of nucleotides indivisible by 3; tay sachs - duchennes MD
Because carbamaoyl phosphate is involved in both urea cycle and pyrimidine synthesis

8. What are the three mc autosomal trisomies in decreasing order?
can be d/t lyonization
Prolonged Ab use
Downs (21) - Edwards (18) - Pataus (13); also in increasing severity
Glutamine PRPP amidotransferase

9. Is DNA acidic or basic?
TFs
When the disease manifestation depends on from who the gene deletion was inherited from d/t methylation that occurs; Prader Willi and AngelMann
Flourescent DNA/RNA In SITU hybridization; for visualization of anomalies (like microdeletions) that are too small to be seen on karyotype; Prader - Willi syndrome
Acidic

10. What type of vitamin is Vit D? Where do we get it? in What form?
Karyotyping
Fat soluble; either endogenous production or exogenous; D2 ergocalciferol is ingested from plants and D3 cholecalciferol is formed in sun exposed skin (and can be consumed in fortified milk)
Arginne
A folic acid analogue

11. What are the only substrates for gluconeogenesis? and What products are convertible to it?
Inhibits lipoic acid; lipoic acid is a cofactor for pyruvate dehydrogenase
Pyruvate (through OXA); lactate - alanine - malate (and all other TCA intermediates through OXA) - glycerol - odd chain fatty acids yield propionyl coA Which can be converted to succinyl coA and enter as TCA cycle
Nucleus
Vit D levels

12. What is the defect that causes Alport's Syndrome? What is the most common inheritance pattern? What are the three mc clinical presentations?
5'--> 3'; prokaryote only; for removing RNA primer and filling it with DNA
Glutamate
Type IV collagen defect; X linked recessive; hereditary glomerulonephritis - deafness - ocular disturbances
Lysine and arginine; basic

13. What is loss of heterozygosity? Name an example.
When the 2nd hit of the allele is What causes the disease; sporadic retinoblastoma
Differentiation of cells - vision in reduced light (retinol makes up rhodopsin cells) - antioxidant
Pyruvate to lactate (results in lactic acidosis and decreased pyruvate for oxaloacetate for gluconeogenesis) - increased production of glycerol 3 phosphate from DHAP for TG synthesis; and increased betahydroxybutyrate ketoacid production from increas
It contains the peptidyltransferase activity (for elongation of protein

14. Where do aminotransferase reactions occur? and What vitamin cofactor do they require?
It induces its action!
In hepatocytes; B6
Steroid synthesis and detoxification
Which dimerizes and activates a protein phosphatase Which de phosphorylates glycogen phosphorylase

15. From What aa does serotonin come from? What NT is serotonin a precursor for?
Tryptophan; melatonin
Griseofulvin
Sickle cell disease - conversion of hydroophillic glutamic acid to hyrdophobic valine
Autosomal Dominant; NF1 and mit. diseases (variable expression) - ?

16. Vitamin c is needed in...
Mebendazole and thiabendazole
Trimethroprim inhibits bacterial dihyrofolate reductase
catecholamine synthesis (dopamine to norepinephrine)
Lactating mammary glands - adrenal cortex (sites of fatty acid or steroid synthesis) - RBCS (for glutathione reduction for FR injury)

17. What cofactor is required of preprocollagen hydroxylation?
Vit C
NF2 - DiGeorge/Velocardiofacial syndromes
Osteoblasts; de phosphorylates pyrophosphate Which inhibits bone mineralization; bone mineralization
XR - iduronate sulfatase

18. The plasma membrane...
Promoter binds RNA Pol II and is very close (25 bases) to initiation site and is AT rich; enhancer/silencers bind TFs only - can be located close or far and regulate gene expression but not specifically initiation; transcription
Lyonization; nondisjunction in mitotic divisions during embryonic period
is asymmetric
2 NADH - 2 ATP - 2 pyruvate - 2H+ - 2H20

19. What are the three main cytoskeletal elements?
all carriers
AD
Acetyl coA; gluconeogenesis
Actin/myosin - MT - intermediate filaments

20. What carries electrons (as energy)?
Urea cycle enzyme deficiency (mc: ornithine transcarbamoylase); liver disease - alcoholic cirrhosis and reye's
Mental retardation - obesity - short stature - hypogonadism - hypotonia - hyperphagia; father
NADH - NADPH - FADH2
Back up of pyruvate and alanine and thus lactic acidosis occurs; can be d/t alcoholism (vit B1 def)

21. Name two antineoplastic drugs that work by inhibiting the mitotic spindle by MT blocking.
Conversion to UDP glucose via UDP glucose pyrophosphorylase; glycogen synthase (rate limiting step )
Vincrstine (vinca alkaloids) and paclitaxel
When the 2nd hit of the allele is What causes the disease; sporadic retinoblastoma
LDL; LDL oxidize atherosclerosis

22. What is one steroid that increases gluconeogenesis? What else does cortisol do that yields hyperglycemia?
Cortisol; inhibits insulin action
5' capping (with 7 methylguanosine) - 3' adenylation - splicing of introns; nucleus
25 OH D3; 1 -25 (OH)2 D3 (Calcitriol)
Endonucleases are specific and break specific linking phosphodiester bonds - exonucleases are not sequence specific and just remove the nucleoside

23. What are the findings in Metachromatic leukodystrophy?
Assist in spontaneous refolding of proteins
Central and peripheral demyelination with ataxia and dementia
Dactinomycin - doxorubicin
1 for all three classes of RNA; Rifampin; TB

24. What is the pathogenesis of Goodpasteurs syndrome? What are the main targets?
Mental and growth retardation; seizures - fair skin - eczema - musty body odor; neurotoxic ketones and acids stimulate vomitting - can lead to pyloric stenosis
Edwards
Abs against type IV collagen; pulmonary and glomerular capillaries
Phenylethanolamine N- methyl transferase; SAM

25. What is def of Vit E caused by?
When different combination of exons get combined together; in Beta thallasemia
Fat malabsorption (CF) and abetalipoproteinemia (damage takes up all antioxidants)
Yes! congenital simply means 'born with'- hereditary is familial
Increased orotic acid in urine - megaloblastic anemia - +/- hyperammonemia

26. What is the precursor in the skin that the sun turns to D3?
Tyrosine hydroxylase; tetrahydrobiopterin factor; NADP+
Increased NADH causes lactate production and pyruvate dehydrogenase def causes increased lactate (d/t thiamine def that often occurs with alcoholics)
7 dehydrocholesterol
They use the H2O2 produced by some bacteria to produce bleach with myeloperoxidase Which they still have

27. What vit def occur from antibiotic use?
Milder form of type 1 with normal blood lactate levels; debranching enzyme (alpha -1 -6 glucosidase)
All and Alzheimers
Antineoplastic agents; alkylate DNA!; cyclophosphamide and nitrosurea (aka lomustrine - a nitrosource)
Biotin (vit B7) and Vit K

28. How many stages are there in HMP shunt? Where do they occur? how much energy does HMP shunt use up?
MT!
COP II
Developmental delay - gargoylism - airway obstruction (d/t short neck) - corneal clouding - CAD - hepatosplenomegaly
2 oxidative and nonoxidative; cytoplasm (both); none (none produced either - you are simply switching carriers of energy- from glucose 6 phosphate to NADPH)

29. What are permanent cells? Which cells are permanent?
Silent - misssense - nonsense
Cells that stay in G0 and cannot replicate - instead they regenerate from stem cells; neurons - skeletal and cardiac muscles - and RBCs
30S ribosomal RNA (small one)
teratogenic

30. What is the source of Vitamin B1? What is its other name? What causes a deficiency in B1?
Fructose bisphosphatase 2
DiGeorge and Velocardiofacial; deletion on chromosome 22q11 results in aberrant dev of 3rd and 4th branchial pouches; digeorge has thymic and parathyroid prob - velocardiofacial has palate and facial instead
The active form of Vit D (1 -25 (OH)2 D3)
Enriched whole grain cereals and other things; thiamine; malnutrition (nonenriched white processed bread and rice) and alcohol second to malnutrition

31. From What aa does niacin come from? with What vitamin cofactor?
NAD+; through ETC you produce NAD+; through production of Lactate from pyruvate you create lactate
Pyruvate to lactate (results in lactic acidosis and decreased pyruvate for oxaloacetate for gluconeogenesis) - increased production of glycerol 3 phosphate from DHAP for TG synthesis; and increased betahydroxybutyrate ketoacid production from increas
Tryptophan; B6
Lysine and arginine; basic

32. What is the reason for blue sclerae in Osteogenesis Imperfecta?
Via fructose 1 P by fructokinase in the liver; as glucose 1 by being GALT- ed ;)
Excreted from the kidney in the form of urea in hepatocytes
Thinned cornea from lack of connective tissue so see underlying choroidal lens
Either salvage by HGPRT and PRPP or conversion to xanthine and then uric acid by xanthine oxidase

33. Where is type 1 collagen found?
Bone - Skin - Tendon - dentin - fascia - cornea - late wound repair
Do agarose gel eletrophoresis to separate the different sizes of the PCR products (sizes id the the fragment)
2 -4 dinitrophenol - aspirin - and thermogenin (in brown fat)
Avidin in raw egg whites prevents their reabsorption; also antibiotic use; dermatitis - alopecia - glossitis - lactic acidosis - enteritis

34. What does a def in folic acid cause? is it more or less common than cobalamin def? How do you differentiate it with cobalamin def?
Fat soluble; either endogenous production or exogenous; D2 ergocalciferol is ingested from plants and D3 cholecalciferol is formed in sun exposed skin (and can be consumed in fortified milk)
Histidine; B6
Macrocytic megaloblastic anemia; it is the most common vit def in the US; no neuro symptoms and no methylmalonyl coA in the urine
Acetone

35. What are the findings of homocystinuria?
Pellagra
Increased homocysteine in the urine - mental retardation - osteoporosis - marfanoid habitus - and atherosclerosis
Vit K; neonates have sterile intestine and can not synthesize vit K
BM; laminins; most flexible; different aa composition

36. list three uncoupling agents
Cytosine to uracil
Each codon specifies only one amino acid
2 -4 dinitrophenol - aspirin - and thermogenin (in brown fat)
Ile - Phe - Thr - Trp

37. Glucagon works on __________ to activate glycogenolysis by activating adenylyl cyclase
Meiotic nondisjunction in mothers gametes during the first meiosis
liver
Phosphoenolpyruvate; pyruvate kinase; fructose 1 - 6 BP; ATP - alanine
catecholamine synthesis (dopamine to norepinephrine)

38. What is the first step in the respiratory burst/oxidative burst? in What disease is this deficient?
NADPH oxidase; CGD
AD
Matrix; intermembrane space
Multiple bone fractures - blue sclerae - hearing loss (abdnormal middle ear bones!) - dental imperfections - retarded wound healing

39. What causes fat soluble vitamin deficiencies?
Malabsorption problems (CF and sprue) and mineral oil intake
Osmotic diarrhea - bloating - cramps
Gets converted to glycerol 3 P Which is then converted to DHAP Which then can enter glycolyis
Vitamin B1 (thiamine) - Vitamin B2 (riboflacin) - Vitamin B3 (niacin) - Vitamin B5 (pantothenate) - Vitamin B6 (pyridoxine) - Vitamin B7 (Biotin) - Vitamin B12 (cobalamin) - folate - Vit. C

40. What is the primary source of nitrogen in the urea cycle
Dihydrofolate reductase; vitamin B12; homocysteine
Glutamate
Gets converted to pyruvate via the Cori cycle in the liver
Marfans and emphysema; marfans is a fibrillin protein defect - fibrillin is a supporting protein in tropoelastin scaffolding and results in aorta - skeletal and eye defects; emphysema is due to a deficiency in the function of alpha 1 antitrypsin

41. What does the brain do with ketone bodies?
Metabolizes them with transferase enzymes to acetyl coA
Insertion or deletion of a number of nucleotides indivisible by 3; tay sachs - duchennes MD
all are diseased!
Structural (constitutively active)

42. What does ornithine transcarbamyolase do to carbamoyl phosphate?
Alpha 1 -4 linkages; alpha 1 -6 linkages
Converts it to citrulline
Increased CPK and muscle biopsy
Glycolysis and aerobic respiration

43. Insulin receptor is not cAMP second receptor but rater tyrosine kinase...
Do agarose gel eletrophoresis to separate the different sizes of the PCR products (sizes id the the fragment)
High glycogen in muscle - but cannot break it down - leading to painful muscle cramps - myoglobinuria with strenuous exercise - no increase in lactic acid after exercise; skeletal muscle glycogen phophorylase
Which dimerizes and activates a protein phosphatase Which de phosphorylates glycogen phosphorylase
The active form of Vit D (1 -25 (OH)2 D3)

44. What is the inheritance pattern of hereditary spherocytosis?
When water is pulled in; polyols (sugar alcohols); cataracts - retinopathy - peripheral neuropathy all seen in chronic hyperglycemia in diabetes
AD
Increased blood levels of ammonia - decreased BUN
Each codon specifies only one amino acid

45. What are the symptoms of arsenic poisoning?
ATP depletion and highly aerobic tissues (heart and brain) are affected first; false - glucose infusion worsens
Oxaloacetate depleted for gluconeogenesis; excess NADH shunts oxaloactetate towards malate
Increased blood levels of ammonia - decreased BUN
Vomiting - rice water stools - garlic breath

46. Which is the most common lysosomal storage disease? What are its findings?
Gauchers; hepatosplenomegaly - aseptic necrosis of the femur - bone crises - Gauchers cells - crumpled tissue paper looking (fibrillar appearing macrophages in liver - spleen - b.m.)
Glycolysis and aerobic respiration
Galactokinase deficiency and classic galactosemia; classic galactosemia
Yes! congenital simply means 'born with'- hereditary is familial

47. When is phenylketonuria screened? why?
Schwann cells - lens - retina - kidneys because they only have aldose reductase and no sorbital dehydrogenase
2-3 days after birth because maternal enzyme during fetal like might still be there
Reticulin - skin - blood vessels - uterus - fetal tissue - early phase of granulation tissue
Galactose

48. Amino acids are found in...
Proprionyl coA; through methylmalonyl coA; B12
only L form
AD
In ability to reabsorb phosphate from renal tubular cells results in osteomalacia due to defective bone mineralization; no

49. What is vitamin B7? What is its main job? in What reactions?
Lens and neural tissue; converts galactose to osmotically active galactitol
Glucagon - insulin and epinephrine
When the disease manifestation depends on from who the gene deletion was inherited from d/t methylation that occurs; Prader Willi and AngelMann
Biotin; cofactor for carboxylation; pyruvate carboxylase (turning pyruvate to oxaloacetate) - acetyl coA carboxylase (acetyl coA to malonyl Co A) - and proprionyl coA caroboxylase for (propionyl CoA to methylmalonyl coA)

50. 'Initiation' of protein tranlsation is activated by ATP hydrolysis. T/F?
Lysine and leucine
tyrosine hydroxylase
False; GTP hydrolysis
Lys and arg

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USMLE Step 1 Biochemistry

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