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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. Name two antineoplastic drugs that work by inhibiting the mitotic spindle by MT blocking.
Karyotyping
is active
Vincrstine (vinca alkaloids) and paclitaxel
Avidin in raw egg whites prevents their reabsorption; also antibiotic use; dermatitis - alopecia - glossitis - lactic acidosis - enteritis

2. What type of enyzmes are used in base excision repair?
When different combination of exons get combined together; in Beta thallasemia
To supply sufficient glucose to the brain and the RBCs and to preserve protein
Glycosylases (only remove the base - cut the bond between ribose and base)
Orotic aciduria megaloblastic anemia can not be corrected with folic acid or vit B12

3. What are the findings in Krabbes disease?
Peripheral neuropathy - developmental delay - optic atrophy - globoid cells
Hepatic glycogenolysis (mostly) - also hepatic gluconeogenesis - adipose release of FFA (minor)
Branching increases the rate of synthesis and breakdown of glycogen by having more sites to add on to and break off
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)

4. What carries 1 carbon units as energy?
Tetrahydrofolates
Cytoplasmic side; active
plasma membrane
teratogenic

5. What converts pyruvate to Acetyl CoA ? What allosterically downregulates this enzyme?
Glucagon - insulin and epinephrine
Pyruvate dehydrogenase; ATP - NADH - acetyl CoA
Schilling test
Converts it to citrulline

6. How many ATP does aerobic metabolism of glucose produce? depending On what? What tissues use which?
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)
XR - iduronate sulfatase
32 or 30; malate aspartate shuttle or glycerol 3 phosphate shuttle; heart/liver and muscle
Citrulline is combined with aspartate to make arginosuccinate Which is then split into fumarate (which leaves to enter TCA) and arginine. Arginine is then converted to Ornithine (via arginase) giving off Urea Which then goes to the kidney and ornithi

7. Which water soluble vitamins get stored in the liver with the fat soluble vitamins? Which has a greater pool of storage in the liver? Where do all the other water soluble vitamins go?
Gets converted to glycerol 3 P Which is then converted to DHAP Which then can enter glycolyis
Becomes methionine
Neimann pick and tay sachs
B12 and folate; B12; washed out

8. What type of exonuclease activity does DNA polymerase I have? in What organisms is it found? What is it used for?

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9. What are the resp. clinical symptoms of CF?
Thick mucus plugs lungs recurrent pulmonary infections (pseudomonas and aureus) - chronic bronchitis - bronchiectasis (which can lead to cor pulmonale!); biofilms form on resp tract
Oxaloacetate gets shifted to malate d/t excess NADH
Highly condensed forms of DNA; mitosis; neoplasia - highly dividing and thus hyperchromatic
Cafe au lait spots - optic pathway gliomas - lisch nodules - scoliosis - neural tumors

10. What is the product of alpha ketoglutarate dehdrogenase?
Hereditary defect of renal tubular amino acid transporter for cysteine - ornithine - lysine and arginine in the PCT of kidnyes
Succinyl coA
Increased CPK and muscle biopsy
Cu; hydroxylation

11. What is the deficient enzyme in Von Gierkes disease? What are the findings?
Edwards
Thinned cornea from lack of connective tissue so see underlying choroidal lens
Severe fasting hypoglycemia - very high levels glycogen in liver - high blood lactate - hepatomegaly
Conversion to UDP glucose via UDP glucose pyrophosphorylase; glycogen synthase (rate limiting step )

12. The three steps of PCR
fat
1. denature by heating 2. during cooling anneal with DNA primers 3. elongation - add heat stable DNA polymerase 4. repeat
Glycine; heme
Lesch Nyhan syndrome; X linked recessive

13. Achondroplasia is associated with advanced ________ age
Glutamate; glutamate decarboxylase; B6; gamma aminobutyrate
COP II
Arg - lys - his; positive except His has no charge at body pH
paternal

14. Is hexokinase or glucokinase activated by insulin?
Glutamate
UV specific endonucleases for excision repair; AR; dry skin - photosensitivity - poikiloderma - susceptibility to skin cancers
5' capping (with 7 methylguanosine) - 3' adenylation - splicing of introns; nucleus
Glucokinase

15. What cofactor does acetyl coA carboxylase require? What does it convert?
Flourescent DNA/RNA In SITU hybridization; for visualization of anomalies (like microdeletions) that are too small to be seen on karyotype; Prader - Willi syndrome
Biotin; rate limiting step in fA synthesis - acetyl coA into malonyl coA
Converts it to citrulline
Respiratory burst - P450 - and glutathione reductase

16. What is lebers hereditary optic neuropathy? What is the main clinical symptom? and What is its mode of inheritance?
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!!
1) if it is stable/labile or permanent 2) intact BM and 3) intact ECM
Degeneration of retinal ganglion cells and axons; acute loss of central vision; mit. inheritance
Intestine - renal - bone

17. What is the order of cell cycle phases? What happens in each phase?
Lactose (glucose and galactose)
Vit D levels
Mitosis then Interphase (G1 - S - G2); in G1 is presynthesis phase - S is synthesis phase (DNA rep. etc) - G2 is premitotic (making of MT spindle etc)
Gets converted to pyruvate via the Cori cycle in the liver

18. What are stable/quiescent cells? Which cells are stable?
A topoisomerase II inhibitor; because cancer cells use II more so than healthy cells
Chloramphenicol
Trinucleotide expansion diseases
They can enter G1 from G0 and replicate if they like; hepatocytes - lymphocytes - fibroblasts

19. What are the cofactors required for pyruvate dehydrogenase?
Collagen; fibroblasts; 4; ECM
TPP (from B1- pyrophosphate) - FAD (B2) - NADH2 (B3) - CoA (B5 - panothenate) - Lipoic Acid
XR - iduronate sulfatase
Phenylalanine hydroxylase or tetrahydrobiopterin factor

20. When are there low levels of cAMP? What does this result in?
Actin/myosin - MT - intermediate filaments
Phosphofructokinase 1; fructose 1 phosphate to fructose 1 -6 bisphosphate; enhancers: AMP - fructose 2 -6 Bisphosphate; downregulators: citrate - ATP
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!!
NADPH oxidase; CGD

21. What can cause a def in vit D?
Renal failure - decreased sun - fat malabsorption - chronic liver disease - p450 induction - hypoparathyroidism (activates 1 alpha hyrdoxylase)
Heteroplasmy
Hepatic glycogenolysis (mostly) - also hepatic gluconeogenesis - adipose release of FFA (minor)
are AR

22. Only muscle and brain have transferase enzyme that converts ketone bodies to...
3 hydrogen bonds; 2 hydrogen bonds
Inability to taste
acetyl coA
Pyridoxine; converted to pyridoxal phsophate used in transamination reaction - decarboxylations - heme synthesis - niacin synthesis from trp - glycogen phosphorylase - cystathionine synthesis - NT synthesis

23. What happens to homocysteine after converting a methyl?
Arginine
Vit C deficiency; glossitis - anemia - weakened vessels - hemorrahges - hemarthroses - swollen gums - bruises -
Becomes methionine
Mitochondria - archaebacteria - mycoplasma - and some yeasts

24. Heterozygous females in X linked recessive disease...
can be d/t lyonization
are AR
The lack of lysosomal proteins (are secreted - default from RER!) results in macromolecules accumulating in lysosomes - inclusions cause pathology
Renal calculi of uric acid (replaces uric acid in excretion)

25. What is the rate limiting step in fatty acid synthesis? What four things inhibit this rate limiting step? What stimulates it?
Von gierkes
Urea cycle enzyme deficiency (mc: ornithine transcarbamoylase); liver disease - alcoholic cirrhosis and reye's
Lysine and arginine; basic
Acetyl coA carboxylase converting Acetyl coA into malonyl coA; increased AMP - glucagon - epinephrine - palmitate; citrate

26. What is the effect of defiiency of VIt E?
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
Marfans - homocystinuria - MEN 2B
Uric acidemia; HGPRT; purine salvage
Lime and CaCO3 to displace the niacin

27. What does the passage of electrons in the ETC result in?
NAD+; through ETC you produce NAD+; through production of Lactate from pyruvate you create lactate
Lupus
1 for all three classes of RNA; Rifampin; TB
Formation of a proton gradient that is then used to create ATP through ATP synthase

28. What Abs block the binding between aminoacyl tRNA and rRNA by binding the 30S ribosome?
SnRNPs; RNA polymerase III
G6PD dehydrogenase; transketolases
Aminoglycosides and tetracyclines
When the disease manifestation depends on from who the gene deletion was inherited from d/t methylation that occurs; Prader Willi and AngelMann

29. What is the treatment of hyperammonia?
RER; free ribosomes
in hepatocytes
Limit protein in diet; give benzoate or phenylbutyrate Which bind amino acids and lead to excretion - lactulose (hydrogen ion binds to ammonia to make excretable ammonium) and neomycin (to kill bacteria that release ammonia from aa)
kidney

30. Is PRPP added later or first in pyrimidine synthesis?
Cell signaling defect in FGF receptor resulting in dwarfism and short limbs with normal head and trunk; AD
Hepatic glycogenolysis (mostly) - also hepatic gluconeogenesis - adipose release of FFA (minor)
Constitutive - random insertion of gene into mouse genome; conditional - targeted through homologous recombination
Later

31. What 4 diseases specifically results with B1 deficiency?
Phenylalanine build up
1) Dry beriberi: peripheral neuropathy demyelination (symmetricul muscle wasting) 2) Wernicke: ataxia - confusion - nystagmus - mammilary body and medial dorsal nuc of thalamus hemorrhage 3) Korsakoff: anterograde and retrograde amnesia - demyelinati
Uric acidemia; HGPRT; purine salvage
Stored ATP - creatine phosphate - anaerobic glycolysis; as distances increase - ATP is obtained from additional resources; above plus ox phos

32. Where are secreted proteins synthesized? Where are cellular/organellar proteins synthesized?
RER; free ribosomes
Pantothenate; essential comp of CoA (needed for acyl transfers) and fatty acid synthase
Glycogen phosphorylase; phosphorylation and dephosphorylation
To transfer methyls; a methionine and an ATP; norepinephrine plus a methyl makes epinephrine

33. What is a common result of unbalanced robertsonian translocation?
Depression - progressive dementia - choreiform movements; between the ages of 20 and 50
Oral uridine administration; provides nucleosides and provides feedback inhibition
Chromosomal imbalance (downs for ex)
osteosarcomas (Rb mutation is in all cells)

34. What are labile cells? Which cells are labile?
Gets converted to glycerol 3 P Which is then converted to DHAP Which then can enter glycolyis
When one allele on a gene is only expressed and the other is methylated/inactivated; during gametogenesis one of the alleles is methylated because the gamete from the other sex will provide those characteristics for the child
Night blindness - dry skin
Cells that never got into G0 and divide rapidly with a short G1; bone marrow - gut epithelium - hair follicles - skin

35. We can't use even chain fatty acids for blood glucose or else we would all...
1 for all three classes of RNA; Rifampin; TB
be anorexic
Riboflavin makes up FAD and FMN both used in redox reactions; vegans
Developmental delay - gargoylism - airway obstruction (d/t short neck) - corneal clouding - CAD - hepatosplenomegaly

36. What is the metabolism of fructose?
Decreased substrate for gluconeogenesis (pyruvate to lactate and not oxaloacetate); and pyruvate doing only lactic acidosis and not glycolysis
Consumption of bear liver - and overtreatment isoretinoin; constitutional symptoms and alopecia and skin changes
homocysteine transferase
Fructose gets phosphorylated into fructose 1- P by fructokinase and then fructose 1P gets metabolized into DHAP or glyceraldehyde by aldolase B

37. How would one use a PCR to id an RNA virus?
Von gierkes
Phosphofructokinase 1
Do an RT PCR (reverse transcriptase)- RT the RNA first - then PCR the DNA
Distinctive elfin faces - mental retardation - hypercalcemia d/t sensitivity to vit D - well developed verbal skills and extreme friendliness - CV problems

38. What causes the pathology in I- cell disease? What does I cell sidease
Lack of proper dietary therapy during pregnancy resulting in infant's microcephaly - mental retardation - growth retardation and congenital heart defects
Succinate hydrogenase; matrix
The lack of lysosomal proteins (are secreted - default from RER!) results in macromolecules accumulating in lysosomes - inclusions cause pathology
Acidic

39. What is the main form of glycogenolysis after glycogen phosphorylase? What happens instead in some lysosomes? does this process use glycogen phosphorylase? in What disease is this enzyme deficient?
Helps make Vit K and antioxidant
Familial Adenomatous Polyposis (APC gene)
Debranching enzyme; alpha 1 - 4 glucosidase; no!; Pompes disease
Creates nicks in DNA to prevent supercoiling; both!

40. What is the mode of inheritance for the multiple endocrine neoplasias?
Zero order; increased production of NADH no matter the amount of end products produced
AD
Homocysteine; homocysteine methyltransferase with B12 and tetrahydrofolate
Macrocytic megaloblastic anemia; it is the most common vit def in the US; no neuro symptoms and no methylmalonyl coA in the urine

41. give an example of how phenylketonuria is pleiotropic.
Phosphofructokinase 1
Pataus
Also have fair skin - blond hair - blue eyes - eczema
NADH - NADPH - FADH2

42. What dose a deficiency in Vit B12 cause? What causes it?
N linked oligosaccharides
Macrocytic megaloblastic anemia - hypersegmented PMNs - subacute combined degeneration myelopathy Which results in degeneration of the dorsal and lateral columns (loss of position and vibration sense - spastic paresis and ataxia) due to abnormal myel
Liver mit and liver cytosol
Uses HMG coA reductase

43. list three uncoupling agents
NADH - Acetyl CoA - ATP; NAD+ - ADP and Ca2+
Ile - Phe - Thr - Trp
2 -4 dinitrophenol - aspirin - and thermogenin (in brown fat)
Formation of the alpha chains out of glycine - lysine - proline in the RER to make preprocollagen; hydroxylation of the proline and lysine residues in the RER; glycosylation of the lysine residues to make procollagen Which is triple helix of alpha ch

44. What disease is associated with chromosome 15?

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45. What enzyme is involved in the degradation of tyrosine to fumarate?
Hexosaminidase A; GM2 ganglioside
pleiotropic
Homogentistic acid oxidase
severe

46. What are two examples of X linked Autosomal Dominant disease?
Pyruvate dehydrogenase; ATP - NADH - acetyl CoA
Hypophosphatemia rickets and Alports
Dark connective tissue - brown pigmented sclera - debilitating athralgias; homogentistic acid builds up and can be toxic to cartilage
Coenzyme A and lipoamides

47. What contributes to the acidosis in alcoholism?
Using serine (which turns into glycine after reaction)
Because carbamaoyl phosphate is involved in both urea cycle and pyrimidine synthesis
Type IV collagen defect; X linked recessive; hereditary glomerulonephritis - deafness - ocular disturbances
Lactic acidosis and ketoacidosis

48. What is the major cause of B12 def? What is the clinical picture of this?
Pernicious anemia; older - mentally slow european woman who is anemic and icteric with a smooth shiny tongue and has broad based shuffling gait
Multiple bone fractures - blue sclerae - hearing loss (abdnormal middle ear bones!) - dental imperfections - retarded wound healing
alk phos
X linked recessive; deletion of the dystrophin gene (connects actin to the membrane glycoprotein) due to frame shift mutation - lack of dystrophin results in muscle breakdown Which gets replaced by fibrofatty tissue and collagen

49. Prokaryotes have What ribosomal units?
SAM; Vit C
Succinate hydrogenase; matrix
Kartaganer's aka ciliar dyskinesia; lack of dynein arm ATPase
30S + 50S= 70S

50. What is the first step in glycolysis?
Phosphorylation of glucose
Inability to taste
Codons may encode same amino acid since there are only ~20 aa
A cytoskeletal protein - apart of flagella - cilia - mitotic spindles and transport (in neurons for example)

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USMLE Step 1 Biochemistry

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