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Biochemistry

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1. Describe the location and fxn of the Na/K ATPase
1 ring
P+q = 1
Plasma membrane - 3Na out - 2K in - ATP on cytoplasmic side
D2 = ergocalciferol - ingested from plants D3 = cholecalciferol - ingested from milk - formed in sun exposed skin

2. What enzyme converts glucose 1 p to UDP glucose
CTG
De novo pyrimidine synthesis and urea - ornithine transcarbamoyl def in the urea cycle leads to a build of CP - then converted to orotic acid in pyrimidine synthesis pathway
UDP glucose pyrophosphorylase
Skin

3. Acetyl - CoA carboxylase catalyzes what rxn
Robertsonian translocation and mosaicism
Inc vit B6
Acetyl - CoA to malonyl - CoA (2C to 3C)
17 - 17 letters in von Recklinghausen

4. Which amino acids are elastin rich in
Proline and glycine (non glycosylated forms)
Breaks down acyl - coa to acetyl coa groups in mito
Hypercalciuria - loss of appetite - stupor - seen in sarcoidosis from activation fo vit D by epithelioid macrophage
BOne

5. Which step in the de novo purine and pyrimidine synthesis pathway requires just aspartate
Protein
Phosphorylation - glycosylation - hydroxylation
Orotic acid to UMP
Protective against malaria

6. In what direction are DNA and RNA synthesized

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7. Broadly - What can cause fat - soluble vitamin deficiencies
Glycine - aspartate - glutamine
In mitochondria - pyruvate to oxaloacetate - requires biotin - ATP - activated by acetyl coA
CarTWOlage
Malapsorption syndromes like sprue or CF or mineral oil intake

8. What sugar is sorbitol converted to and via what enzyme - and What can happen in cells lacking this enzyme
Fructose via sorbitol dehydrogenase - inc sorbitol leading to osmotic damage as in cataracts - retinopathy - peripheral neuropathy as in diabetes
Convulsions - hyperirritability - peripheral neuropathy - deficiency inducible by INH and oral contraceptives - sideroblastic anemais
Transfers methyl units
Alpha - ketoglutarate dehydrogenase complex

9. What enzyme catalyzes the rxn from pyrvuate to Acetyl - CoA and what inhibits it
Dermatitis - alopecia - enteritis
After day 1
Malonyl coa (+ biotin= palmitiate - 1 16C fatty acid)
Pyruvate dehydrogenase - ATP - NADH - acetyl - CoA

10. What is a nonsense mutation
Cori's - debranching enzyme alpha 1 -6 glucosidase - gluconeogenesis intact
Metachromatic leukodystrophy - arylsulfatase A - cerebroside sulfate AR
Antigen - antibody reactivity - can look for antigen or antibody in patients blood
Change resulting in early stop codon

11. What enzyme degrades a small amount of glycogen in lysosomes
Orotic acid phosphoribosyltransferase or orotidine 5'- phosphate decarboxylase
Glutamine PRPP amidotransferase
1- capping on 5' (7- methyguanosine) 2 - polyadenylation on 3' end 3 - splicing out of introns
Alpha 1 -4 glucosidase

12. What activates the pyruvate dehydrogenase complex
Exercise: inc NAD/NADH - inc ADP - inc Ca
Citrate - isocitrate - alpha ketoglutarate - succinyl - CoA - succinate - fumarate - malate - oxaleoacetate
Arg and his inc in histones Which bind negatively charged DNA
Night blindness - dry skin

13. What is the limiting reagent in EtOH metabolism
NAD+
CFTR gene - 7 - Phe 508
Consesus sequenec of base pairs
Galactitol - galactose appears in blood and urine - can cause infantile cataracta - AR

14. What does the mutation in the gene cause in protein synthesis
Core proteins
NADH - NADPH - FADH2
Muscle
Abnormal protein folding - degradation before reaching cell surface

15. What are the two possible causes of albinism
17 - 17 letters in von Recklinghausen
Inhibits EtOH dehydrogenase and is an antidote for methanol and ethylene glycol poisoning
Lack of tyrosinase (no melanin) AR ordefective tyrosine transporters (less tyrosine) - can results in lack of migration of NC cells
TTP

16. What does an umabiguous genetic code refer to...
Severity of disease worsens or age of onset of disease is earlier in succeeding generations - huntingtons
Tuberous sclerosis
Progressive hreditary nephritis and deafness - associated with occular disturbances - due to abnl type IV collagen - usually x- linked recessive
Each codon specifies only 1 amino acid

17. What defects characterize DiGeorge syndrome
Fasting
Thymic - parathyroid and cardiac
ATP
Breaks down acyl - coa to acetyl coa groups in mito

18. What is pseudohypertrophy in the calf a result of - and What are the cardiac manifestations
Ornithin transcarbamoylase def - x linked recesssive - other urea cycle enzymes defs are autosommal recessive
Colchicine
Collagen
Fibrofatty replacement of muscle - cardiac myopathy

19. What step begins the urea cycle and What is the enzyme needed - Where does it happen
Presence of both nl and mutated mtDNA resulting in mitochondrial inherited disease
Removal of N or C termal propeptides from zymogens to generate mature proteins
CO2 + NH4 needs carbamoyl phosphate synthase I - in the mitochondria
Post to neg

20. Where is glucose 6 phosphatase found and What does it do
Loss of brush border enzyme causing bloating - cramps - osmotic diarrhea
In ER - glucose 6- P to glucose
Adenylyl cycle - inc cAMP - inc PKA - glycogen phosphorylase kinase activated - glycogen phosphoylase active - glycolysis
Mucus secreting globlet cells and antibody secreting plasma cells

21. What apolipoprotein is on LDL
B100
Many generations - both male and female affected - often pleiotropic - can present clinically after puberty
Enhancers
Result from phagocytic removal of heinz bodies my macs - G6PD def

22. What components come together to make S- adenosyl methionine
FMR1 gene - methylation - associated with chromosomal breakage
Fibroblast
Antibiotic use or excessive ingestion of raw eggs
ATP and methionine

23. Gene imprinting implies that How many alleles are active at a single locus
One
B100 and E
Reads usual codon but inserts wrong AA
Same AA - often base change in 3rd position of codon (tRNA wobble)

24. What is the Name and function of vit B2
Riboflavin - cofactor in oxidation and reduction (FAD and FMN are derived from riboflavin)
ATP and alanine
Retardation - self mutilation - aggression - hyperuricemia - gout - choreoathetosis
Connective tissue

25. What is variable expression and What is an example
Met - val - arg his
Neurons
VMA
Nature and severity of phenotype vary from 1 individual to another - NF type 1

26. What is the activated carrier for methyl groups
Lacks glucose 6 phophatase
SAM
P2 +2pq+ = 1
Adipse tissue stores - keton bodies become the main source of energy fo the brain and heart - after these are depleted - vital protein degradation accelerates - leading to organ failure and death

27. When are glycogen reserves depleted
Mutated dystrophin gene - less severe - adolescence
RER - translation of alpha chains - usually Gly-X-Y polypeptide (preprocollagen)
After day 1
Purines= A - G pyrimidine = C - T (U)

28. What are the complications/signs of familial hypercholesterolemia
Microarrays
AMP - fructose 2 -6 BP
Sever atherosclerotic disease early in life - and tendon xanthomas on the achilles - MI may develop before 20
Inhibits acetaldehyde dehydrogenase and contributes to hangover symptoms

29. What causes Hartnup's disease
Convulsions - hyperirritability - peripheral neuropathy - deficiency inducible by INH and oral contraceptives - sideroblastic anemais
Breaks down acyl - coa to acetyl coa groups in mito
RER - translation of alpha chains - usually Gly-X-Y polypeptide (preprocollagen)
AR disorder characterized by defective neutral amino acid transporte on renal and intestinal epith cells

30. If two alleles are present - but the active allele is deleted - what happens
Cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms - floppy mitral valve - subluxation of lenses
Disease
Silencers
Catalase positive (catalase neg produce H2O2 the cell can use) like S. aureus or aspergillus

31. What is the breakdown product of dopamine
VMA
HVA
Poor defense from oxidizing agents - fava beans - sulfonamides - primaquine - antituberclosis drugs leadig to hemolytic anemia.
Locus heterogeneity - ocular albinism is x- linked recessive

32. Which type of chromatin is condensed - transcriptionally inactive - sterically inaccessible?
O- oligosaccharaides
Liver - ovaries - seminal vesicles
Heterochromatin = HighlyCondensed
Adipse tissue stores - keton bodies become the main source of energy fo the brain and heart - after these are depleted - vital protein degradation accelerates - leading to organ failure and death

33. What are the function of vit C
Cystathionine synthase def - dec affinity of cystathionine synthase for pyridoxal phosphate - homocystein methyltransferase def
Inc permeability of membrane causing a dec in proton gradient and inc in O2 consumption - ATP synthesis stops - but electron transport continues to produce heat
Antioxidant - facilitates iron absorption by keeping iron in the Fe2+ reduced state - necessary for hydroxylation of proline and lysine collagen bridges - necessary for dopamine beta hydroxylase which converts DA to NE
Ribulose 5P to ribose 5P - G3P and F6P - transketolase and B1

34. Pts with albinism are at inc risk For what cancer
Antibiotic use or excessive ingestion of raw eggs
D2 = ergocalciferol - ingested from plants D3 = cholecalciferol - ingested from milk - formed in sun exposed skin
Dermatitis - alopecia - enteritis
Skin

35. Which bond is stronger AT or CG and why? What is the laboratory consequence of this?
Dec in alpha ketoacid dehydrogenas leading to blocked degredation of branches amino acids like Ile - Leu - and Val - severe CNS defects mental retardation and death
Loss of brush border enzyme causing bloating - cramps - osmotic diarrhea
Familial hypercholesterolemia - hyperlipidemia type IIA
CG- 3 > AT-2 - More CG content - melting point goes up

36. What is disulfiram used for
ATP hyrdolysis couple to energetically unfavorable rxns
Inhibits acetaldehyde dehydrogenase and contributes to hangover symptoms
25OHD3
Initial is heterogenous nuclear RNA - the capped and tailed is called mRNA

37. What do neurofilaments stain for
Degradation of TG stored in adipocytes
Inhibits 50S peptidyltransferase
Q -
Neurons

38. What tissues have both enzymes of sorbitol metabolism
DNA
No mutation occuring at the locus - no selection for any genotypes at the locus - completely random mating - no migration
Liver - ovaries - seminal vesicles
Transfers cholesterol from mature HDL to VLDL - IDL and LDL (cholesterol ester transfer protein)

39. Delivers dietary TGs to peripheral tissues - delivers cholesterol to liver in the form of remnants - mostly depleted of TGs - secreted by intestinal epith cells
Chylomicrons
Medial dorsal nucleus of thalamus - mamillary bodies
Oxidative is irreversible
Citrate - acetyl coa from mito to cyto

40. How is ATP used by the cell
ATP hyrdolysis couple to energetically unfavorable rxns
BOne
Poly A polymerase - signal is AAUAA
Pyroxidine - converted to pyroxidine phosphate a cofactor used in transamination - decarboxylation - glycogen phosphorylase - cystathionine synthesis and heme synthesis - required for synthesis of niacin and tryptophan

41. What is anticipation and give an example
Removal of N or C termal propeptides from zymogens to generate mature proteins
Severity of disease worsens or age of onset of disease is earlier in succeeding generations - huntingtons
Thymic - parathyroid and cardiac
Chylomicrons

42. What are the fat soluble vitamins and What does their absorption depend on...
Anabolic processes like steroid and fatty acid synthesis - respiratory burst - P-450 - glutathione reductase
P2 +2pq+ = 1
ADEK - dependent on gut (ileum) and pancreas - accumulate in fat and can cause toxicity
Ca/calmodulin in muscle to coordinate with muscle activity

43. What are the findings with homocystinuria and What amino acid is needs to be supplemented
Locus heterogeneity - ocular albinism is x- linked recessive
2 rings
Homocystein in ruine - mental retardation - osteoporosis - tall stature - kyphosis - lens subluxation and atherosclerosis leading to stroke and MI - cysteine
Dopamine beta hydroxylase

44. Fluorescent DNA or RNA probe binds to specific gene of interest - used for specific localization of genes and direct visualization of anomalies - like microdeletions - at molecular level
Tay- Sachs - hexosaminidase A - GM2 ganglioside - AR
De novo pyrimidine synthesis and urea - ornithine transcarbamoyl def in the urea cycle leads to a build of CP - then converted to orotic acid in pyrimidine synthesis pathway
Via 1 proprionyl - CoA which can enter the TCA as succinyl - CoA and undergo gluconeogenesis
FISH

45. What happens in vit K def
Neonatal hemorrhage with inc PT and PTT - but nl bleeding time - can also occur after prolonged use of broad spectrum Abx
Base + ribose + phosphate (3' -5') phosphodiester bond
Hydroxyurea - inhibits ribonucleotide reductase - 6 MP - blocks de novo purine synthesis - 5 FU inhibits thymidilate synthase - MTX - inhibits DHFR - Trimethroprin inhibits bacterial DHFR
Myeloperoxidase

46. Which phase of the HMP shunt is reversible and Which is irreversible
Exerts a dominant effect - a heterozygote produces a nonfxnal altered protein that also prevents the normal gene from functioning - mutation of Tx factor its allosteric site - nonfxning mutant can still bind DNA - preventing wild type Tx from binding
Euchromatin
Oxidative is irreversible
Inability to transport LCFAs into mitochondria results in toxic accumulation causing weakness - hypotonia - hyperketotic hyperglycemia

47. What is mosaicism and give an example
Inherited lysosomal storage disorder; failure of addition of mannose 6 phosphate to lysosomal proteins - enzymes secreted outside of cell instead of lysosomes
Seals.
Occurs when cells in the body have different genetic makeup - can be germline mosaic - which may produce a disease that is not carried by parents somatic cells - lyonization - random X inactivation in females
Medial dorsal nucleus of thalamus - mamillary bodies

48. How do odd chain fatty acids participate in gluconeogenesis
By inhibiting formation of the initiation complex and cause misreading of mRNA
Glutamine PRPP amidotransferase
Mental retardation - growth retardation - seizures - fair skin - eczema - musty body odor
Via 1 proprionyl - CoA which can enter the TCA as succinyl - CoA and undergo gluconeogenesis

49. What does the golgi do to sugars in proteoglycans and of selected tyrosine on proteins
Alpha - ketoglutarate dehydrogenase complex
Oral uridine administration
Sulfation
Robertsonian translocation and mosaicism

50. Which anticancer drugs work on microtubules
Hepatic glycogenolysis - adipose tissue release of FFA - muslce and liver FFA - hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and proprionyl - coA (odd chain FFA)
Aberrant 3rd and 4th branchial arches causing 22q11 deletion - cleft palate - abnl facies - thymic dysplasia - cardiac defects - hypocalcemia secondary to parathyroid aplasia
Vincritsine/vinblastine
Cheilosis - inflammation of lips - scaling and fissures at the corner of the mouth - corneal vascularization

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Biochemistry

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