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USMLE Step 1 Biochemistry

Subjects : health-sciences, usmle-step-1

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1. From What aa does glutathione come from?
P53 and Rb; p53 activates BAX Which inhibits BCL2 When there is DNA damage - Rb phosphorylation allows progression into S phase
Glutamate
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
Mucus secreting goblet cells - ab secreting plasma cells - nt secreting neurons

2. What is ascorbic acid? What is its 5 main function?
TPP (from B1- pyrophosphate) - FAD (B2) - NADH2 (B3) - CoA (B5 - panothenate) - Lipoic Acid
Urine turns black on standing
Vitamin C; facilitates iron absorption by making sure its in its reduced state (Fe2+) - hydroxylation for lysine and proline Which is necessary for crosslinking; necessary for dopamine Beta hydroxylase for conversion of dopamine to NE; keeps FH4 in i
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

3. What are the findings in pyruvate dehydrogenase def? How do you treat it
3 hydrogen bonds; 2 hydrogen bonds
Vit C
Tyrosine
Neurologic defects - myopathy - lactic acidosis; giving ONLY ketogenic nutrient high fat content and aa (lysine and leucine)

4. What is the difference between a nucleotide and a nucleoside?
Insertion or deletion of a number of nucleotides indivisible by 3; tay sachs - duchennes MD
Hemolytic anemia due to heinz bodies Which are oxidized hemoglobin precipitating within the RBCs
Nucleoside is just the ribose plus the base; nucleotide is the ribose plus the base but the phosphate bond
AAUAAA; Poly A polymerase; no

5. What disease is associated with chromosome 21?

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6. What does SAM turn into after it loses a methyl? How does it get turned back to SAM?
Cytoplasmic side; active
Pellagra (dermatitis - diarrhea - dementia); INH use - B6 deficiency - Hartnup disease - malignant carcinoid syndrome - and a corn based diet (lacks trp and niacin in corn cant be absorbed)
6MP blocks de novo purine synthesis
Homocysteine; homocysteine methyltransferase with B12 and tetrahydrofolate

7. What do enhancers/silencers bind?
Dopamine
Hemolytic anemia with a blood smear with heinz bodies and bite cells (phagocytic removal of heinz bodies)
TFs
Pulmonary - GI - reproductive (infertility in male due to absence of vas deferens and seminal fluid thickness)

8. What is etoposide? why does this not affect normal healthy cells?
Isoleucine - valine - leucine
Pellagra
Inability to transport LCFA into mitochondria results in their build up and causes weakness - hypotonia And HYPOKETOTIC HYPOGLYCEMIA
A topoisomerase II inhibitor; because cancer cells use II more so than healthy cells

9. What is uniparental disomy? give an example of a disease it can cause.
When child gets two chromosomes from one parent; imprinting dx
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
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST); alanine to pyruvate and aspartate to oxaxloacetate
Cri du Chat

10. What luminal secretions are affected in CF? What is wrong with the secretions?
Thinned cornea from lack of connective tissue so see underlying choroidal lens
Branche aa alpha ketoacid dehydrogenase; thiamine; Isoleucine - leucine - valine
Stored ATP - creatine phosphate - anaerobic glycolysis; as distances increase - ATP is obtained from additional resources; above plus ox phos
Respiratory - seminal fluid - pancreatic - gallbladder; very thick without NaCl to pull water

11. What is the exception to degeneracy in the genetic code?
Tryptophan; niacin
Thick mucus plugs lungs recurrent pulmonary infections (pseudomonas and aureus) - chronic bronchitis - bronchiectasis (which can lead to cor pulmonale!); biofilms form on resp tract
Aldolase B
Methionine is only encoded by AUG

12. What is the function of Vit D?
Highly condensed forms of DNA; mitosis; neoplasia - highly dividing and thus hyperchromatic
To increase serum Ca and Phosphate for ultimate bone deposition by: increase intestinal absorption of calcium and phosphate (also renal); and increase resorption of bone by stimulating macrophages (osteoclasts)
When the 2nd hit of the allele is What causes the disease; sporadic retinoblastoma
Prevents neural tube defects in 1st trimester

13. What aa degradation disorder results in atherosclerosis? debiltating arthralgias? osteoporosis?
Homocystinuria (homocysteine damages endothelial cells); alkaptonuria (tyrosine degradation); homocystinuria
Neurons and RBCs
paternal
Pellagra (dermatitis - diarrhea - dementia); INH use - B6 deficiency - Hartnup disease - malignant carcinoid syndrome - and a corn based diet (lacks trp and niacin in corn cant be absorbed)

14. Where is type IV collagen found? to What protein is bound? What is special about this type? How do the different types of collagen differ?
Dermatitis - glossitis - diarrhea
Renal calculi of uric acid (replaces uric acid in excretion)
TCA cycle - FA oxidation - acetyl coA production; ox phos
BM; laminins; most flexible; different aa composition

15. How do you differentiate causes of megaloblastic anemia?
Orotic aciduria megaloblastic anemia can not be corrected with folic acid or vit B12
long saturated fatty acids
Ascites from liver damage
Osteomalacia is vit D def seen in adults and causes bowed legs and results in increased fractures

16. What two compounds provide the two N's of urea? What else is in urea other than two NH2's?
Glutamate and aspartate; CO2 provides an ketone
Endonucleases - exonucleases - DNA polymerase - DNA ligase
Cardiomegaly and systemic findings leading to early death; lysosomal alpha -1 -4- glucosidase (acid maltase)
Colchine

17. What converts dUMP to dTMP? What drug blocks this?
Fruits and vegetables
Thymidylate synthase; 5- Flourouracil
An allosteric regulator; fructose 1 phosphate; phosphofructokinase 2
degradation

18. In What stage of the cell cycle must cells be in order to be analyzed for karyotyping? and From What fluids can you draw the cells? and for What is karyotyping is used for?
Metaphase (all lined up); blood - bone marrow - amniotic fluid - placental tissue; used to diagnose chromosomal abnormalities (deletions - trisomies - sex chromosomal disorders)
Def in Vit C; def in Vit D
Where there is insulin; low protein kinase A means dePhosphorylation of the complex Which results in increased PFK2 Which results in more fructose 2 -6 bp and thus more PFK1!!
Isocitrate dehydrogenase

19. How is the nitrogen of amino acids transferred to the liver for the urea cycle? explain this process.
Dopamine beta hydroxylase; vit C
As alanine; amino acids donate their amino group to alpha ketoglutarate making it glutamate and the aa then becomes an alpha ketoacid (joins TCA cycle); glutamate then converts pyruvate to alanine by donating its amino group to pyruvate (with ALT); a
Lesch Nyhan syndrome; X linked recessive
Decreased phenylalanine - increase tyrosine

20. Where are cilia found? What symptoms are associated with kartageners syndrome?
Uses HMG coA reductase
Hungtington
Cells that are stable go in and out of the G1 to G0 Which is the stable/quiescent (can go into replication but dont) type of cells; cells that stay in G0 are permanent and can not enter G1
In the reproductive tract and in the resp tract; infertility - bronchiectasis and recurrent sinusitis - associated with situs inversus

21. Loss of heterozygosity is the rule for...
long saturated fatty acids
Von gierkes
Convulsions - hyperirritiability - peripheral neuropathy - sideroblastic anemias; alcoholics and INH and fortified goats milk consumption
tumor suppressor genes (p53 - Rb - BAX)

22. In the fasting state - What ensures that the pyruvate doesnt get used for TCA cycle?
degradation
Chronic pancreatitis leads to type 1 diabetes - pancreatic insufficiency leads to ADEK deficiencies - malabsorption and steatorrhea - blocked gallbladder ducts leads to secondary biliary cirrhosis
Ehler Danlos; type III collagen def; joint dislocation - berry aneurysm - ecchymoses - organ rupture
The products of FA oxidation (Acetyl CoA and NADH) phosphorylate pyruvate deyhdrogenase Which inactivates it

23. 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?
Carbomyl phoshpate synthetase I
Macrocytic megaloblastic anemia; it is the most common vit def in the US; no neuro symptoms and no methylmalonyl coA in the urine
Cardiomegaly and systemic findings leading to early death; lysosomal alpha -1 -4- glucosidase (acid maltase)
Nacetyl cysteine; breaks disulfide bridges of mucus plugs

24. What disease is associated with chromosome 13?
Ascites from liver damage
Deficiencies in one of the many lysosomal enzymes results in accumulation of abnormal metabolic products
To increase serum Ca and phosphate for bone deposition
Pataus

25. What does alcohol do to the P450 system?
By epoxide reductase in the liver; coumadin; intestinal flora and leafy vegetables
Isocitrate dehydrogenase
Induction in chronic alcoholism (increases tolerance); inhibition in acute alcoholism
Galactose gets converted to galactose 1 Phosphate by galactokinase Which then gets turned into glucose 1 phosphate by Galactose 1 Uridyl Transferase (GALT) Which also produces UDP Gal Which is used for lactose production in the breast; the fate of gl

26. What are the clinical symptoms of NF1?
Cafe au lait spots - optic pathway gliomas - lisch nodules - scoliosis - neural tumors
Southern - DNA - Northern - RNA - Western - Protein; blotting procedures are used to detect a specific nucleic acid or aa sequence; the sample is electrophoresed and then transferred to a filter Which is then soaked in a denaturant and then a radiola
Abs against type IV collagen; pulmonary and glomerular capillaries
By cyclin CDK complexes

27. What disease is associated with chromosome 4?
Hungtington
7 dehydrocholesterol
Carnitine acyltransferase I
Fat malabsorption (CF) and abetalipoproteinemia (damage takes up all antioxidants)

28. Which vesicular trafficking protein takes vesicles from the Golgi to the ER (retrograde)?
glutton
Heart - SKELETON - and EYES: arachnodactyly - long limbs - cystic medial necrosis of aorta resulting in aneurysms (and eventual dissection) - floppy mitral valve (prolapse and regurg!) - subluxation of lens
Niemann pick and Tay Sachs; hepatosplenomegaly or not
COP I

29. Name two proapoptotic/tumor suppressor genes. How do they each act?
NADH - NADPH - FADH2
Hexosaminidase A; GM2 ganglioside
P53 and Rb; p53 activates BAX Which inhibits BCL2 When there is DNA damage - Rb phosphorylation allows progression into S phase
Milder form of type 1 with normal blood lactate levels; debranching enzyme (alpha -1 -6 glucosidase)

30. What is the impetus for ketoacidosis in starvation? alcoholism?
Oxaloacetate depleted for gluconeogenesis; excess NADH shunts oxaloactetate towards malate
Pernicious anemia; older - mentally slow european woman who is anemic and icteric with a smooth shiny tongue and has broad based shuffling gait
UV specific endonucleases for excision repair; AR; dry skin - photosensitivity - poikiloderma - susceptibility to skin cancers
Prevents neural tube defects in 1st trimester

31. RER adds ___________ to asparagines
Prevents neural tube defects in 1st trimester
As alanine; amino acids donate their amino group to alpha ketoglutarate making it glutamate and the aa then becomes an alpha ketoacid (joins TCA cycle); glutamate then converts pyruvate to alanine by donating its amino group to pyruvate (with ALT); a
Aminoglycosides and tetracyclines
N linked oligosaccharides

32. Even chain fatty acids can not produce new glucose since they...
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)
NADPH- reductive biosynthesis!
Neimann pick and tay sachs
only yield acetyl coA

33. What is the reason for blue sclerae in Osteogenesis Imperfecta?
Thinned cornea from lack of connective tissue so see underlying choroidal lens
CCA and chemically modified bases Where amino acid is covalently bonded
Induction in chronic alcoholism (increases tolerance); inhibition in acute alcoholism
Vit C; Vit E

34. What is the result of lactase deficiency? in What nationalities is it seen the most?
Macrocytic megaloblastic anemia; it is the most common vit def in the US; no neuro symptoms and no methylmalonyl coA in the urine
Increased CPK and muscle biopsy
Lack of lactase (brush border enzyme) so can not break down lactose (a dissaccharide of galactose and glucose); African Americans and Asians
AD; disorder of blood vessels that results in telangietasias - skin discolorations - and AVMs (arteriovenous malformations)

35. What are three ways to poison Ox phos?
Arg and his
fatty acid degradation
Cleft palate - Abnormal faces - thymic aplasia (t cell def) - Cardiac defects - hypocalcemia (secondary to hypoparathyroid); 3rd and 4th branchial pouch aberrant development
Electron transport inhibitors - ATPase inhibitors - Uncoupling agents (increase permeability of the membrane - loss of hydrogen gradient)

36. In protein translation - What is the 'A' site for? 'P' site? 'E' site? What is the exception to this?

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37. What is elastin? How is it different from collagen? Where is it found? How is it broken down?
Homocysteine; homocysteine methyltransferase with B12 and tetrahydrofolate
A fibrous protein (ie produced by fibroblasts); it has lysine and proline but nonglycosylated; arteries - lungs - elastic ligaments - vocal cords - ligamenta flava (connect vertebrae); broken down by elastase Which is inhibited by alpha 1 antitrypsin
3 hydrogen bonds; 2 hydrogen bonds
Delayed wound healing - hypogonadism - decreased adult hair - dysgeusia - anosmia - and alcoholic cirrhosis - perioral rash

38. From What aa do the catecholamines come from? and What aa does that aa come from?
Tyrosine; phenylaline
Decrease intake of fructose and sucrose (fructose and glucose)
Galactose 1 phosphate uridyltransferase (GALT) results in an accumulation of toxic substances; failure to thrive - jaundice - hepatomegaly - infantile cataracts - mental retardation; exclude galactose and lactose from diet
succinyl coA (and then to OXA)

39. What is loss of heterozygosity? Name an example.
Mitochondrial inheritance
Riboflavin; dairy and meat
When the 2nd hit of the allele is What causes the disease; sporadic retinoblastoma
Ouabain

40. Which form of iron is most absorbable? What form is non heme ingested iron in (vegetables for ex)?
When different combination of exons get combined together; in Beta thallasemia
Arylsulfatase A; cerebroside sulfate
Fe2+; Fe3+
Tyrosine

41. Which amino acids are required during periods of growth?
Bilateral acoustic schwannomas - juvenile cataracts
Flourescent DNA/RNA In SITU hybridization; for visualization of anomalies (like microdeletions) that are too small to be seen on karyotype; Prader - Willi syndrome
Citrate is positive on it - AMP and fructose 2 -6 bisphosphate is negative on it; gluconeogenesis
Arg and his

42. What is the rate determining enzyme in glycogenolysis?
Glycogen phosphorylase
Pyridoxine; converted to pyridoxal phsophate used in transamination reaction - decarboxylations - heme synthesis - niacin synthesis from trp - glycogen phosphorylase - cystathionine synthesis - NT synthesis
Dopamine beta hydroxylase; vit C
Using serine (which turns into glycine after reaction)

43. How many RNA polymerases do prokaryotes have? What drug blocks prokaryotic RNA polymerase only? What is it used for?
Sulfonamides - primaquine - dapsone - antiTB drugs - fava beans - LDL; RBCs
1 for all three classes of RNA; Rifampin; TB
Dihydropterin reductase; NADP+; phenylalanine to tyrosine and tyrosine to DOP
Glucokinase

44. What is the effect of defiiency of VIt E?
Alpha 1 -4 linkages; alpha 1 -6 linkages
Hemolytic anemia (fragility of RBCs) - muscle weakness and posterior column and spinocerebellar tract demyelination (neuron damage) resulting in decreased proprioception and vibration sensation - and peripheral neuropathy - and retinal degeneration
NADH - Acetyl CoA - ATP; NAD+ - ADP and Ca2+
Ortinithine transcarbamoylase - orotic acid phosphoribosyltransferase - and orotidine 5 phosphate decarboxylase; urea cycle; last two are involved in conversion of orotic acid to UMP (adding PRPP to orotic acid)

45. What converts dihydrobioterin back to tetrahydrobioterin factor? What energy carrier is used? in What reactions is this cofactor used?
Aromatic; musty body odor
dimers
Dihydropterin reductase; NADP+; phenylalanine to tyrosine and tyrosine to DOP
VHL (Von Hippa Lindau)

46. Which antifungal acts on MT?
Oral uridine administration; provides nucleosides and provides feedback inhibition
Heart - SKELETON - and EYES: arachnodactyly - long limbs - cystic medial necrosis of aorta resulting in aneurysms (and eventual dissection) - floppy mitral valve (prolapse and regurg!) - subluxation of lens
Griseofulvin
adrenal medulla

47. What is the rate determining enzyme in HMP shunt?
Griseofulvin
Fe2+; Fe3+
ATP
Glucose 6 phosphate dehydrogenase

48. _____________ prevents fluidity of plasma membrane
activation of PFK1
Phenylalanine hydroxylase or tetrahydrobiopterin factor
Stored ATP - creatine phosphate - anaerobic glycolysis; as distances increase - ATP is obtained from additional resources; above plus ox phos
high cholesterol

49. What are the common symptoms of B vitamin deficiencies?
Dermatitis - glossitis - diarrhea
Meconium ileus and failure to thrive; negative serum immunoreactive trypsin
Alpha 1 -4 linkages; alpha 1 -6 linkages
Lens and neural tissue; converts galactose to osmotically active galactitol

50. What is the most common disorder of the urea cycle? What is the result? What is its mode of inheritance? What is the mode of inheritance of the other urea cycle enzyme def?
Progressive neurodegeneration (spasticity d/t UMN disease) - hepatosplenomegaly - cherry red spot on macula - foam cells
Peripheral neuropathy - developmental delay - optic atrophy - globoid cells
Ornithine transcarbomyalse; orotic aciduria; X linked recessive; autosomal recessive
Urea cycle enzyme deficiency (mc: ornithine transcarbamoylase); liver disease - alcoholic cirrhosis and reye's

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USMLE Step 1 Biochemistry

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