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Polish I · High-ROI Weak Points

Your weakpoints (ChatGPT finals review) × the high-yield analysis. Drill in ROI order: kinetics, folate/B12/one-carbon, purines/pyrimidines, lipoproteins (Tier 1) · AA/urea, PPP, cholesterol (Tier 2) · vitamins+cofactors, mol bio (quick points). Colored to the study-book guide.

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1. Front

   Km equals the substrate concentration at what fraction of Vmax ?
   Back

   [S] at ½ Vmax . Low Km = high affinity ; high Km = low affinity .
2. Front

   Which enzyme parameter is the turnover number — molecules of substrate converted per second by one saturated enzyme, independent of [E]?
   Back

   kcat . Intrinsic to the enzyme. Contrast: Vmax = kcat × [E]total , which scales with enzyme amount.
3. Front

   Write the equation linking Vmax , kcat , and total enzyme .
   Back

   Vmax = kcat × [E]total . Double the enzyme → double the Vmax; kcat is unchanged (intrinsic).
4. Front

   Which single ratio expresses catalytic efficiency (performance at low, non-saturating [S] )?
   Back

   kcat / Km . Diffusion-limited ceiling ≈ 10⁸–10⁹ M⁻¹s⁻¹ .
5. Front

   Competitive inhibitor — effect on Km and Vmax ?
   Back

   Km UP (apparent), Vmax SAME . Inhibitor resembles substrate and fights for the active site .
6. Front

   Reversible inhibitor: Km increased , Vmax unchanged . Which type?
   Back

   Competitive . The only reversible type that spares Vmax .
7. Front

   Noncompetitive inhibitor — effect on Km and Vmax ?
   Back

   Km SAME , Vmax DOWN . Binds an allosteric site , not the active site; ES still forms but ESI can't turn over.
8. Front

   Reversible inhibitor: Vmax decreased , Km unchanged . Which type?
   Back

   Noncompetitive (kinetically identical to irreversible ). Cannot be rescued by excess substrate.
9. Front

   Uncompetitive inhibitor — effect on Km and Vmax ?
   Back

   Km DOWN and Vmax DOWN (both, by the same factor). Inhibitor binds only the ES complex .
10. Front

    Inhibitor with Km DOWN and Vmax DOWN (both decrease) — which type?
    Back

    Uncompetitive . Binds ES only → traps it as dead-end ESI, lowering apparent Km while killing Vmax.
11. Front

    An inhibitor binds only to the ES complex (not free enzyme). Name the type and its LB signature.
    Back

    Uncompetitive . On Lineweaver-Burk: parallel line (slope unchanged), shifted up and to the left .
12. Front

    On a Lineweaver-Burk plot, the y-intercept = ? and the x-intercept = ?
    Back

    y-intercept = 1/Vmax ; x-intercept = −1/Km . Trap: a higher y-intercept means a lower Vmax (reciprocal).
13. Front

    Competitive inhibition on Lineweaver-Burk — how do the intercepts move?
    Back

    y-intercept SAME (1/Vmax unchanged); x-intercept shifts right toward 0 (less negative → larger apparent Km). Slope increases ; line rotates about the y-intercept .
14. Front

    Noncompetitive inhibition on Lineweaver-Burk — how do the intercepts move?
    Back

    x-intercept SAME (−1/Km unchanged); y-intercept rises (1/Vmax up → lower Vmax). "Same x-intercept, different y-intercept" = noncompetitive .
15. Front

    Lineweaver-Burk: line has the same x-intercept but a higher y-intercept than control. Which inhibition?
    Back

    Noncompetitive — same x-intercept = same Km ; higher y-intercept = lower Vmax .
16. Front

    Lineweaver-Burk: line has the same y-intercept but a less-negative x-intercept than control. Which inhibition?
    Back

    Competitive — same y-intercept = same Vmax ; x-intercept toward 0 = higher apparent Km .
17. Front

    Lineweaver-Burk: inhibited line is parallel to control, shifted up and left. Which inhibition?
    Back

    Uncompetitive — slope unchanged, both Km and Vmax down. "Parallel lines" is the mnemonic.
18. Front

    Can competitive inhibition be overcome by adding more substrate ?
    Back

    Yes — flood with substrate to out-compete the inhibitor; Vmax is reached. (Noncompetitive and uncompetitive: cannot be rescued.)
19. Front

    How does an irreversible inhibitor differ from noncompetitive on kinetics alone — and the real distinction?
    Back

    Kinetically identical: Vmax down , Km unchanged . Distinction: irreversible forms a covalent bond — washing out the inhibitor or adding substrate does NOT restore activity; recovery needs new enzyme synthesis.
20. Front

    What is the central carrier of one-carbon units that the entire one-carbon economy runs on?
    Back

    Tetrahydrofolate (THF) — the reduced, active form of folate (vitamin B9) .
21. Front

    Which enzyme reduces dietary folate → DHF → THF , and what reducing cofactor does it use?
    Back

    Dihydrofolate reductase (DHFR) , using NADPH . (Blocked by methotrexate .)
22. Front

    Which THF derivative is the major source of one-carbon units , and which reaction produces it?
    Back

    N5,N10-methylene-THF — produced by the serine → glycine reaction via serine hydroxymethyltransferase (SHMT) (needs PLP + THF).
23. Front

    N5,N10-methylene-THF is consumed by which enzyme , to make which product for DNA?
    Back

    Thymidylate synthase converts dUMP → dTMP , oxidising THF to DHF (which DHFR must regenerate).
24. Front

    Which THF derivative is the methyl donor used to regenerate methionine from homocysteine ?
    Back

    N5-methyl-THF — donates its methyl group to homocysteine via methionine synthase .
25. Front

    Which enzyme regenerates methionine from homocysteine , and which vitamin cofactor does it require?
    Back

    Methionine synthase — requires vitamin B12 (methylcobalamin) , using N5-methyl-THF as the methyl donor.
26. Front

    Methionine synthase transfers a methyl group FROM which donor TO which acceptor?
    Back

    FROM N5-methyl-THF → TO homocysteine , regenerating methionine (+ freeing THF ).
27. Front

    Why can N5-methyl-THF NOT simply be reconverted to other THF forms — what is its only exit?
    Back

    The N5-methyl-THF → THF step is essentially irreversible ; its only exit is through methionine synthase (the B12 step). This is the structural basis of the folate trap .
28. Front

    B12 deficiency : in which single THF form does folate get stranded , and what is this called?
    Back

    Folate is trapped as N5-methyl-THF — the methyl-folate trap . Without B12, methionine synthase stalls and THF can't be recycled into N5,N10-methylene-THF.
29. Front

    Mechanistically, how does the folate trap cause megaloblastic anemia in B12 deficiency?
    Back

    Trapped N5-methyl-THF can't reform N5,N10-methylene-THF → no substrate for thymidylate synthase → no dTMP → DNA replication halts in erythroid precursors.
30. Front

    Deficiency of WHICH vitamin causes homocysteine accumulation ?
    Back

    Either B12 or folate — both feed the remethylation step (B12 runs methionine synthase; folate supplies N5-methyl-THF), so deficiency of either raises homocysteine .
31. Front

    Both B12 deficiency and folate deficiency — which TWO findings do they SHARE?
    Back

    Megaloblastic anemia + elevated homocysteine . (The hematology and the homocysteine look identical.)
32. Front

    Which finding is present in B12 deficiency but NOT in folate deficiency — and is the most sensitive marker?
    Back

    Elevated methylmalonic acid (MMA) — only B12 deficiency raises it (folate is normal). More sensitive than serum B12 itself.
33. Front

    Which B12-only clinical feature distinguishes it from folate deficiency ?
    Back

    Neurological signs — subacute combined degeneration of the spinal cord (demyelination). Folate deficiency alone causes NO neuro disease.
34. Front

    Why does B12 deficiency raise methylmalonic acid but folate deficiency does not?
    Back

    B12 is also the cofactor ( 5'-deoxyadenosylcobalamin ) for methylmalonyl-CoA mutase ( methylmalonyl-CoA → succinyl-CoA ). Folate has no role here, so MMA stays normal in folate deficiency.
35. Front

    The clinical pitfall : why is giving folate alone to a B12-deficient patient dangerous?
    Back

    Folate corrects the megaloblastic anemia but masks the underlying B12 deficiency — the neurological degeneration progresses unchecked . Always rule out B12 before treating with folate alone.
36. Front

    Purine de novo synthesis: the ring is built on what activated starting molecule ?
    Back

    PRPP (phosphoribosyl pyrophosphate). The purine ring is assembled atom-by-atom directly on the ribose scaffold of PRPP — opposite of pyrimidines.
37. Front

    Ring assembled FIRST as a free molecule, THEN attached to PRPP — purines or pyrimidines? (classic trap)
    Back

    Pyrimidines . Ring built free in the cytoplasm first, then bolted onto PRPP. (Purines = ring built on PRPP.)
38. Front

    Which amino acid donates the amide nitrogen at the committed step of purine synthesis (and 2 N total to the ring)?
    Back

    Glutamine (Gln) — its amide N is used by PRPP amidotransferase to make 5-phosphoribosylamine .
39. Front

    Purine de novo: which enzyme catalyzes the committed/rate-limiting step?
    Back

    PRPP amidotransferase — converts PRPP → 5-phosphoribosylamine . Inhibited by AMP, GMP, IMP ; activated by PRPP .
40. Front

    Purine de novo committed step: PRPP amidotransferase — what activates it, what inhibits it?
    Back

    Activated by PRPP (substrate). Inhibited by the downstream products AMP, GMP, and IMP .
41. Front

    Purine branch point: which nucleotide is the common precursor from which both AMP and GMP diverge?
    Back

    IMP (inosine monophosphate). The whole 10-step de novo pathway converges on IMP before branching to AMP or GMP .
42. Front

    IMP → AMP : which energy nucleotide is consumed, and which amino acid is needed? (cross-dependency trap)
    Back

    Needs aspartate and consumes GTP as the energy source. (Making AMP requires GTP — the elegant cross-dependency.)
43. Front

    IMP → GMP : which energy nucleotide is consumed, and which amino acid is needed?
    Back

    Needs glutamine and consumes ATP as the energy source. (Making GMP requires ATP — mirror of the AMP branch.)
44. Front

    Folate cofactor needed at two steps of de novo purine ring assembly (donates 2 carbons)?
    Back

    Formyl-THF (N10-formyl-THF). This is why antifolates like methotrexate cripple purine synthesis too — not just pyrimidines.
45. Front

    Pyrimidine de novo: which enzyme makes carbamoyl phosphate, and where?
    Back

    CPS-II (carbamoyl phosphate synthetase II), in the cytosol . Uses glutamine + CO2 + 2 ATP. Activated by PRPP , inhibited by UTP .
46. Front

    CPS-II vs CPS-I : which uses glutamine vs NH4+ , which compartment, which pathway?
    Back

    CPS-II : glutamine , cytosol , pyrimidine synthesis (activated by PRPP, inhibited by UTP). CPS-I : NH4+ , mitochondria , urea cycle (activated by N-acetylglutamate ).
47. Front

    Pyrimidine de novo: the ring intermediate orotic acid is attached to PRPP, decarboxylated, and yields which mother pyrimidine nucleotide ?
    Back

    UMP . Orotate + PRPP → orotate monophosphate → (decarboxylation) → UMP , the parent of all pyrimidines (→ UDP → UTP → CTP).
48. Front

    Which enzyme reduces ribonucleotides to deoxyribonucleotides, and at which phosphorylation level?
    Back

    Ribonucleotide reductase (RNR) — acts at the NDP level (ADP/GDP/CDP/UDP → dNDPs). Reducing power from NADPH via thioredoxin.
49. Front

    Ribonucleotide reductase activity site: what turns it completely OFF vs keeps it ON ?
    Back

    dATP turns RNR OFF ; ATP keeps it ON . (This is the lever behind ADA deficiency → SCID .)
50. Front

    dUMP → dTMP : which enzyme catalyzes it, and which cofactor donates the methyl group?
    Back

    Thymidylate synthase , using N5,N10-methylene-THF as the methyl donor (oxidized to DHF in the process).
51. Front

    After thymidylate synthase runs, the folate is oxidized to DHF — which enzyme regenerates active THF, using what cofactor?
    Back

    Dihydrofolate reductase (DHFR) , using NADPH . Without it the cycle stalls and dTMP production halts — the target of methotrexate .
52. Front

    Methotrexate — which enzyme does it inhibit, and what two pathways does that shut down?
    Back

    Inhibits DHFR (~1000× tighter than DHF). No THF regenerated → blocks dTMP synthesis (no methylene-THF) AND de novo purine synthesis (no formyl-THF).
53. Front

    5-Fluorouracil (5-FU) — its active metabolite F-dUMP is a suicide inhibitor of which enzyme ?
    Back

    Thymidylate synthase . F-dUMP forms a covalent, irreversible ternary complex with the enzyme + methylene-THF , jamming dTMP synthesis.
54. Front

    Drug-to-target: name the enzyme hit by 5-FU and the one hit by methotrexate .
    Back

    5-FU → thymidylate synthase (via F-dUMP). Methotrexate → DHFR .
55. Front

    Purine salvage : which enzyme recycles hypoxanthine → IMP and guanine → GMP, and which disease is its complete deficiency?
    Back

    HGPRT (hypoxanthine-guanine phosphoribosyltransferase). Complete deficiency = Lesch-Nyhan syndrome (self-mutilation, choreoathetosis, hyperuricemia/gout).
56. Front

    Lesch-Nyhan (HGPRT loss) causes hyperuricemia — by what mechanism (not just "less salvage")?
    Back

    No salvage → PRPP accumulates → over-activates PRPP amidotransferase → de novo purine synthesis runs unchecked → degradation floods out excess uric acid . (Overproduction-type gout.)
57. Front

    Purine degradation: which enzyme oxidizes hypoxanthine → xanthine → uric acid (acts twice)?
    Back

    Xanthine oxidase . Humans lack uricase, so uric acid is the terminal purine catabolite — the reason gout exists in humans.
58. Front

    Xanthine oxidase — name its three cofactors .
    Back

    FAD , molybdenum (Mo) , and non-heme iron . (A flavoprotein — classic 'which mineral?' = molybdenum.)
59. Front

    Gout treatment: allopurinol — what is it an analogue of, and which enzyme does it inhibit?
    Back

    A hypoxanthine analogue. Xanthine oxidase oxidizes it to alloxanthine (oxypurinol) , a suicide inhibitor of xanthine oxidase . Result: more-soluble hypoxanthine/xanthine accumulate instead of urate.
60. Front

    ADA deficiency → SCID: trace the biochemical mechanism.
    Back

    No ADA → dATP accumulates → turns ribonucleotide reductase OFF → no dNDP pools → lymphocytes can't replicate DNA → both T and B cells fail = SCID .
61. Front

    Most common cause of gout (~90% of cases) — overproduction or under-excretion?
    Back

    Decreased renal excretion of urate (~90%), NOT overproduction. (Overproduction types include Lesch-Nyhan and overactive PRPP synthetase.)
62. Front

    Which lipoprotein carries the MOST cholesterol (is the cholesterol-delivery particle)?
    Back

    LDL — core is almost entirely cholesteryl esters ; delivers cholesterol to tissues.
63. Front

    Which lipoprotein is TAG-rich and carries DIETARY fat from the gut, and what is its signature apolipoprotein?
    Back

    Chylomicron — signature apo is ApoB-48 (intestine-only).
64. Front

    Which apolipoprotein is found ONLY on chylomicrons and is made exclusively in the intestine?
    Back

    ApoB-48 — synthesized only in intestinal enterocytes ; it cannot bind the LDL receptor (truncated, lacks the receptor-binding domain).
65. Front

    ApoB-48 vs ApoB-100: tissue of origin, particles carried, and LDL-receptor binding for each?
    Back

    ApoB-48 : intestine -only, chylomicrons only, cannot bind LDL receptor . ApoB-100 : liver -only, stays on VLDL→IDL→LDL, IS the LDL-receptor ligand .
66. Front

    Which lipoprotein is TAG-rich, hepatic (endogenous) fat export , and which apo is its mandatory scaffold?
    Back

    VLDL — made by the liver with ApoB-100 as the obligatory structural scaffold; core is predominantly TAG .
67. Front

    Which lipoprotein mediates reverse cholesterol transport , and what is its main apolipoprotein?
    Back

    HDL — main apo is ApoA-I ; carries cholesterol from peripheral tissues back to the liver.
68. Front

    Which apolipoprotein activates lipoprotein lipase (LPL) , and where does it come from in circulation?
    Back

    ApoCII — obligate activator of LPL ; donated to chylomicrons/VLDL from HDL , then returned to HDL. Without it, LPL sits idle and TAG cannot be cleaved .
69. Front

    Which apolipoprotein is the ligand for remnant (chylomicron remnant / IDL) uptake by the liver?
    Back

    ApoE — recognized by the liver's LDL receptor and LRP for receptor-mediated clearance of remnants and IDL.
70. Front

    Reverse cholesterol transport: which enzyme esterifies free cholesterol in HDL, and what activates it?
    Back

    LCAT (lecithin:cholesterol acyltransferase), activated by ApoA-I — esterifies free cholesterol (fatty acid from lecithin/phosphatidylcholine ) so the cholesteryl ester sinks into the HDL core and matures the particle.
71. Front

    Name the apolipoprotein for each particle (COLD): chylomicron, VLDL, LDL, HDL .
    Back

    Chylomicron → ApoB-48 (+ApoCII, ApoE) VLDL → ApoB-100 (+ApoCII) LDL → ApoB-100 only HDL → ApoA-I (activates LCAT)
72. Front

    After VLDL→IDL→LDL remodeling, which apolipoprotein is the ONLY one left on LDL ?
    Back

    ApoB-100 — LDL has lost all ApoCII and ApoE; only ApoB-100 remains (the LDL-receptor ligand).
73. Front

    Rank the 4 lipoproteins by DENSITY (least → most dense). What inversely tracks with density?
    Back

    Chylomicron < VLDL < LDL < HDL (least → most dense). SIZE is inverse : chylomicrons are largest, HDL smallest — more lipid relative to protein = larger and less dense (fat is lighter than protein).
74. Front

    Which lipoprotein is the LARGEST and LEAST dense , and which is the SMALLEST and densest ?
    Back

    Largest / least dense = Chylomicron (TAG-rich, ~80–500 nm). Smallest / densest = HDL (high protein-to-lipid ratio).
75. Front

    Which receptor clears LDL , what apo does it recognize, and what mechanism internalizes it?
    Back

    The LDL receptor (B/E receptor) recognizes ApoB-100 ; uptake is by receptor-mediated endocytosis in clathrin-coated pits.
76. Front

    Both chylomicrons and VLDL deliver TAG to peripheral tissues. Which enzyme strips the TAG, and which apo activates it?
    Back

    Lipoprotein lipase (LPL) on capillary endothelium , activated by ApoCII — cleaves core TAG into free fatty acids + glycerol .
77. Front

    Which protein transfers cholesteryl esters from HDL → LDL/VLDL (in exchange for TAG)?
    Back

    CETP (cholesteryl ester transfer protein) — moves cholesteryl esters from HDL to LDL/VLDL for eventual LDL-receptor clearance. (Contrast: LCAT esterifies; CETP transfers.)
78. Front

    Free cholesterol delivered by LDL regulates the cell in three ways — name them.
    Back

    (1) Suppresses HMG-CoA reductase (stops synthesis); (2) activates ACAT (re-esterifies cholesterol for storage); (3) downregulates the LDL receptor (limits further uptake).
79. Front

    The remnant of a stripped chylomicron carries which apos, and which organ clears it via which apo?
    Back

    Chylomicron remnant keeps ApoE + ApoB-48 ; the liver clears it via ApoE (LDL receptor + LRP). ApoCII and surface phospholipids are returned to HDL.
80. Front

    Transamination requires which coenzyme , and from which vitamin is it derived?
    Back

    PLP (pyridoxal phosphate) , the active form of vitamin B6 . It is the obligate coenzyme for every aminotransferase .
81. Front

    In transamination, the amino group from most amino acids is transferred onto which acceptor , producing which product ?
    Back

    Acceptor = α-ketoglutarate ; product = glutamate . This funnels the nitrogen of virtually all amino acids into one hub .
82. Front

    Which two amino acids do NOT undergo classical transamination?
    Back

    Lysine and threonine — the two exceptions. (Trap: "all amino acids transaminate" is false .)
83. Front

    Define transdeamination — its two steps and the enzymes/compartments.
    Back

    Transamination (by an aminotransferase , collects N onto glutamate ) + oxidative deamination (by glutamate dehydrogenase in the mitochondria , releases free NH4+ ). It is the major route of nitrogen removal .
84. Front

    Which enzyme releases free NH4+ from glutamate, where, and reducing what cofactor ?
    Back

    Glutamate dehydrogenase (GDH) , a mitochondrial enzyme. It oxidizes glutamate → α-ketoglutarate + NH4+ , reducing NAD+ (or NADP+) to NADH. This is the primary source of free NH4+ in the liver .
85. Front

    How is glutamate dehydrogenase allosterically regulated, and what does it sense?
    Back

    ADP activates (energy-poor → catabolize amino acids); GTP inhibits (energy-rich → no need to burn amino acids). Ties nitrogen catabolism to cellular energy state .
86. Front

    Which aminotransferase generates aspartate for the urea cycle, and by what reaction?
    Back

    AST (aspartate aminotransferase) — transfers an amino group from glutamate to oxaloacetate , making aspartate (the cycle's 2nd nitrogen donor).
87. Front

    On a liver panel: which transaminase is more specific for liver damage vs more sensitive ?
    Back

    ALT = more specific for liver. AST = more sensitive (very high activity inside hepatocytes ). Both rise with cell necrosis .
88. Front

    Urea cycle: which enzyme catalyzes the committed first step, and in which compartment ?
    Back

    CPS-I (carbamoyl phosphate synthetase I) , in the mitochondrial matrix of the liver .
89. Front

    What does CPS-I condense to form carbamoyl phosphate , and at what ATP cost?
    Back

    NH4+ + HCO3− → carbamoyl phosphate , consuming 2 ATP . This nitrogen becomes one of the two nitrogens in urea .
90. Front

    Which activator is obligatory for CPS-I , and what happens without it?
    Back

    N-acetylglutamate (NAG) . Without it, CPS-I is completely inactive — no NAG = no carbamoyl phosphate = the entire cycle stops at step zero . (NAG synthesis is feed-forward activated by arginine .)
91. Front

    CPS-I vs CPS-II — distinguish by location and nitrogen source .
    Back

    CPS-I : mitochondrial , uses NH4+ , → urea. CPS-II : cytosolic , uses amide of glutamine , → pyrimidine synthesis . Mnemonic: CPS- I = m I tochondria; CPS- II = cytosol II c + glutam II ne.
92. Front

    Cytosolic enzyme: makes carbamoyl phosphate for pyrimidine synthesis , uses glutamine , activated by PRPP , inhibited by UTP ?
    Back

    CPS-II .
93. Front

    Urea cycle Reaction 1: ornithine transcarbamoylase (OTC) combines carbamoyl phosphate with ornithine to make what?
    Back

    Citrulline (in the mitochondria ; then exported to the cytosol). OTC deficiency is the most common inherited urea cycle disorder — X-linked recessive .
94. Front

    Urea cycle Reaction 2: which enzyme adds the second nitrogen , from what donor, at what ATP cost?
    Back

    Argininosuccinate synthetase joins citrulline + aspartate → argininosuccinate , using 1 ATP → AMP + PPi (= 2 ATP equivalents ). Aspartate donates the cycle's 2nd nitrogen.
95. Front

    Reaction 3: argininosuccinase cleaves argininosuccinate into which two products, and why is one of them special?
    Back

    Arginine + fumarate . Fumarate is a direct TCA cycle intermediate → links the urea cycle to the TCA cycle (→ malate → oxaloacetate → aspartate, regenerating the 2nd N donor).
96. Front

    Reaction 4 — the only step that directly produces urea: which enzyme, and what else is regenerated?
    Back

    Arginase hydrolyzes arginine → urea + ornithine . Ornithine re-enters the mitochondria to restart the cycle.
97. Front

    Where do the two nitrogens in urea come from? (Name both, precisely.)
    Back

    One from NH4+ (via carbamoyl phosphate, Rxn 1); one from aspartate (Rxn 2). NOT from glutamine, and NOT two NH4+.
98. Front

    What is the total ATP cost per molecule of urea, and how is it split?
    Back

    4 ATP equivalents : 2 ATP at CPS-I + 2 equivalents (ATP → AMP + PPi) at argininosuccinate synthetase . Occurs in the liver .
99. Front

    PPP oxidative phase: which enzyme is the rate-limiting / committed step?
    Back

    Glucose-6-phosphate dehydrogenase (G6PD) — the irreversible, regulated gate; G6PD oxidizes glucose-6-phosphate → 6-phosphogluconolactone .
100. Front

     What is the regulator of G6PD activity (the PPP rate-limiting step)?
     Back

     The NADPH/NADP+ ratio — G6PD is product-inhibited by NADPH ; it accelerates when NADP+ rises (biosynthesis / oxidative stress). NOT ATP/AMP as in glycolysis.
101. Front

     Per glucose-6-phosphate through the oxidative phase, exactly what is produced? (count the NADPH, the sugar, the CO2, the ATP)
     Back

     2 NADPH + 1 ribose-5-phosphate + 1 CO 2 ; no ATP is made.
102. Front

     The two PPP products and their roles: NADPH is for ___ ; ribose-5-phosphate is for ___ ?
     Back

     NADPH = reducing power for biosynthesis + antioxidant defense . Ribose-5-phosphate = the sugar backbone for nucleotide synthesis .
103. Front

     Antioxidant chain — which enzyme uses NADPH to regenerate reduced glutathione (GSH) from GSSG ?
     Back

     Glutathione reductase ( enzyme ) — uses NADPH as the electron donor: GSSG → 2 GSH .
104. Front

     Which enzyme uses GSH to actually neutralize H₂O₂ / ROS?
     Back

     Glutathione peroxidase — GSH → GSSG while reducing H 2 O 2 to water. ( Glutathione reductase then restores GSH using NADPH .)
105. Front

     Why are erythrocytes uniquely dependent on the PPP for antioxidant defense?
     Back

     They have no mitochondria — so the PPP is their only source of NADPH , hence their only way to regenerate GSH and fight oxidative stress.
106. Front

     G6PD deficiency — what disease results, and what hallmark RBC finding?
     Back

     Hemolytic anemia with Heinz bodies (precipitated, oxidized hemoglobin). Episodic, oxidant-triggered — not continuous.
107. Front

     G6PD deficiency : name the classic oxidative triggers of hemolysis.
     Back

     Fava beans (favism), oxidant drugs ( primaquine , dapsone, nitrofurantoin), and infection . Patients are asymptomatic at rest ; hemolysis appears 1–3 days after the trigger.
108. Front

     G6PD deficiency — inheritance pattern and who is predominantly affected?
     Back

     X-linked — males predominantly affected. It is the most common human enzyme deficiency worldwide (~400 million).
109. Front

     Walk the broken chain in G6PD deficiency : no G6PD → ? → ? → hemolysis.
     Back

     No G6PD → no NADPH → glutathione reductase cannot regenerate GSH → ROS accumulate → oxidize Hb ( Heinz bodies ) + membrane → hemolysis .
110. Front

     Which process does NOT require NADPH ? — fatty acid synthesis, cholesterol synthesis, steroid hormone synthesis, β-oxidation
     Back

     β-oxidation — it instead produces FADH 2 and NADH . The other three (all biosynthetic) require NADPH . Classic trap: synthesis vs breakdown.
111. Front

     Besides GSH regeneration and fatty-acid/cholesterol synthesis, name two more major NADPH uses.
     Back

     Ribonucleotide reductase (ribonucleotides → deoxyribonucleotides for DNA) and cytochrome P450 detoxification of drugs/xenobiotics ( liver ).
112. Front

     Oxidative-phase step 2 (hydrolysis of 6-phosphogluconolactone) is catalyzed by which enzyme? What is the planted distractor?
     Back

     6-phosphogluconolactonase ( enzyme ) → 6-phosphogluconate . Trap = phosphohexose isomerase , which is a glycolysis enzyme.
113. Front

     How can a cell make ribose-5-phosphate when it has abundant NADPH and doesn't need the oxidative phase?
     Back

     Run the non-oxidative phase in REVERSE : transketolase + transaldolase pull fructose-6-phosphate + glyceraldehyde-3-phosphate → ribose-5-P. No NADPH made — NADPH is exclusive to the irreversible oxidative phase.
114. Front

     Which non-oxidative PPP enzyme requires a vitamin-derived cofactor , and what is it?
     Back

     Transketolase requires thiamine pyrophosphate (TPP) — vitamin B1. (Thiamine deficiency → beriberi / Wernicke's impairs this phase.)
115. Front

     What is the rate-limiting enzyme of cholesterol synthesis?
     Back

     HMG-CoA reductase (converts HMG-CoA &#8594; mevalonate )
116. Front

     HMG-CoA reductase reduces HMG-CoA to mevalonate using which cofactor ?
     Back

     NADPH (2 molecules)
117. Front

     In which compartment does cholesterol synthesis occur?
     Back

     Cytosol (and ER for the final cyclization stage) &mdash; not mitochondria
118. Front

     Which drug class are competitive inhibitors of HMG-CoA reductase ?
     Back

     Statins (e.g., lovastatin, atorvastatin ) &mdash; they structurally mimic HMG-CoA
119. Front

     By depleting hepatic cholesterol, statins indirectly upregulate which cell-surface receptor &mdash; lowering plasma LDL?
     Back

     LDL receptors on hepatocytes (via SREBP ), pulling LDL out of blood
120. Front

     HMG-CoA reductase is active in which phosphorylation state?
     Back

     Dephosphorylated = active ; phosphorylated = inactive
121. Front

     Which kinase phosphorylates (inactivates) HMG-CoA reductase during energy deficit?
     Back

     AMPK (activated by a high AMP:ATP ratio)
122. Front

     Which hormone activates HMG-CoA reductase (promotes dephosphorylation, fed state)?
     Back

     Insulin &mdash; drives the fed/anabolic state
123. Front

     Which hormone inhibits HMG-CoA reductase (promotes phosphorylation, fasting)?
     Back

     Glucagon &mdash; suppresses cholesterol synthesis when fasting
124. Front

     Cholesterol itself feedback-inhibits its own synthesis through which transcription factor pathway?
     Back

     SREBP (Sterol Regulatory Element Binding Protein) &mdash; high cholesterol retains SREBP-SCAP in the ER , so the reductase gene is not transcribed
125. Front

     When intracellular cholesterol is LOW , what does the SREBP-SCAP complex do?
     Back

     Released from the ER &#8594; travels to Golgi &#8594; cleaved by S2P &#8594; SREBP domain enters nucleus &#8594; upregulates HMG-CoA reductase + LDL receptor genes
126. Front

     Name the THREE independent mechanisms that regulate HMG-CoA reductase .
     Back

     (1) Phosphorylation (covalent), (2) SREBP transcription , (3) proteasomal degradation of the enzyme (triggered by excess cholesterol + bile acids)
127. Front

     Cholesterol synthesis happens in the cytosol, but acetyl-CoA is made in the mitochondria &mdash; and acetyl-CoA cannot cross the inner membrane . How does it reach the cytosol?
     Back

     The citrate shuttle : acetyl-CoA + OAA &#8594; citrate (exported), then cleaved back to cytosolic acetyl-CoA
128. Front

     Which enzyme regenerates cytosolic acetyl-CoA from citrate (consuming 1 ATP)?
     Back

     ATP-citrate lyase (citrate &#8594; acetyl-CoA + OAA)
129. Front

     Cytosolic HMG-CoA commits to which pathway?
     Back

     Cholesterol synthesis (via HMG-CoA reductase &#8594; mevalonate)
130. Front

     Mitochondrial HMG-CoA commits to which pathway, and via which enzyme?
     Back

     Ketogenesis &mdash; via HMG-CoA lyase (NOT reductase)
131. Front

     HMG-CoA &#8594; mevalonate by HMG-CoA reductase. Which pathway / compartment is this?
     Back

     Cholesterol synthesis in the cytosol
132. Front

     HMG-CoA &#8594; acetoacetate + acetyl-CoA by HMG-CoA lyase. Which pathway / compartment is this?
     Back

     Ketogenesis in the mitochondria (liver)
133. Front

     B1 (thiamine) &rarr; which active cofactor , and what reaction type does it run?
     Back

     B1 thiamine &rarr; TPP (thiamine pyrophosphate) ; runs oxidative decarboxylation &mdash; pyruvate dehydrogenase , &alpha;-ketoglutarate dehydrogenase , and transketolase .
134. Front

     Which cofactor /vitamin is required by the PDH , &alpha;-KG dehydrogenase , and transketolase reactions?
     Back

     TPP (thiamine pyrophosphate), the active form of vitamin B1 / thiamine . Mnemonic: TPP runs oxidative decarboxylations .
135. Front

     B2 (riboflavin) &rarr; which two active cofactors , and what chemistry do they do?
     Back

     B2 riboflavin &rarr; FAD and FMN ; flavin redox carriers in oxidoreductases (FAD accepts 2e &minus; + 2H + &rarr; FADH 2 ).
136. Front

     An enzyme needs FAD/FMN . Which vitamin is the precursor?
     Back

     Vitamin B2 (riboflavin) . (Contrast: NAD+/NADP+ come from B3 , not B2.)
137. Front

     B3 (niacin) &rarr; which active cofactors , and what reaction type?
     Back

     B3 niacin / nicotinamide &rarr; NAD + and NADP + ; hydride (H &minus; ) redox carriers in dehydrogenases (NAD + takes 2e &minus; + 1H + &rarr; NADH).
138. Front

     Which vitamin gives rise to NAD + and NADP + ?
     Back

     Vitamin B3 (niacin) . (Bonus: tryptophan can also be converted to nicotinamide for NAD + /NADP + .)
139. Front

     B5 (pantothenate) &rarr; which active cofactor , and what does it carry?
     Back

     B5 pantothenic acid &rarr; Coenzyme A (CoA) ; carries acyl groups (e.g. acetyl-CoA ) &mdash; the acyl-transfer cofactor of transferases .
140. Front

     Which vitamin is the precursor of Coenzyme A ?
     Back

     Vitamin B5 (pantothenic acid) &mdash; CoA carries acyl groups .
141. Front

     B6 (pyridoxine) &rarr; which active cofactor , and what is its signature reaction type?
     Back

     B6 pyridoxine &rarr; PLP (pyridoxal phosphate) ; signature reaction = transamination (also decarboxylations &rarr; bioamines). "Moving, removing, or making a bioamine from an amino acid" = PLP .
142. Front

     A transaminase (e.g. ALT, AST) requires which cofactor , derived from which vitamin?
     Back

     PLP (pyridoxal phosphate) , from vitamin B6 . The amino group is shuttled onto &alpha;-ketoglutarate &rarr; glutamate via a ping-pong mechanism.
143. Front

     B7 (biotin) &rarr; what reaction type, and name its two flagship enzymes ?
     Back

     B7 biotin = CO 2 carrier for carboxylations (ATP-dependent); flagship pyruvate carboxylase and acetyl-CoA carboxylase (ACC) . Covalently bound = prosthetic group .
144. Front

     Which vitamin acts as the covalently-bound CO 2 carrier in carboxylase reactions?
     Back

     Biotin (vitamin B7) &mdash; e.g. pyruvate + CO 2 + ATP &rarr; oxaloacetate (pyruvate carboxylase).
145. Front

     B9 (folate) &rarr; which active cofactor , and what does it carry?
     Back

     B9 folate &rarr; THF (tetrahydrofolate) ; carries one-carbon units for nucleotide synthesis (dTMP) and homocysteine remethylation. (Folate &rarr; DHF &rarr; THF by DHFR .)
146. Front

     The Ser&rarr;Gly reaction loads which exact one-carbon form onto THF , and what uses it?
     Back

     Loads N5,N10-methylene-THF &mdash; the major one-carbon source. Used by thymidylate synthase : dUMP &rarr; dTMP (then THF is oxidized to DHF). Folate deficiency &rarr; no dTMP &rarr; megaloblastic anemia.
147. Front

     B12 (cobalamin) is required for exactly which two enzymes ?
     Back

     Methionine synthase (methylcobalamin; homocysteine + 5-methyl-THF &rarr; methionine ) and methylmalonyl-CoA mutase (5'-deoxyadenosylcobalamin; methylmalonyl-CoA &rarr; succinyl-CoA ).
148. Front

     Which enzyme converts methylmalonyl-CoA &rarr; succinyl-CoA , and which cofactor/form does it use?
     Back

     Methylmalonyl-CoA mutase , using 5'-deoxyadenosylcobalamin (B12) . B12 deficiency &rarr; methylmalonic aciduria (most sensitive marker).
149. Front

     Vitamin K &rarr; what reaction type, and on which proteins?
     Back

     Vitamin K = cofactor for &gamma;-carboxylation of glutamate residues on &gamma;-glutamyl carboxylase 's substrates &mdash; the clotting factors II, VII, IX, X (and proteins C, S). Creates Ca 2+ -binding Gla residues.
150. Front

     Distinguish the role of biotin vs vitamin K &mdash; both touch CO 2 /carboxyl chemistry. Which does which?
     Back

     Biotin = carries CO 2 to add a NEW carboxyl in ATP-dependent carboxylases (pyruvate carboxylase, ACC). Vitamin K = &gamma;-carboxylates EXISTING Glu residues on clotting factors &mdash; no CO 2 -carrier role, no ATP .
151. Front

     Replication: which enzyme unwinds the double helix at the fork by breaking base-pair H-bonds (ATP-driven)?
     Back

     DNA helicase — uses ATP hydrolysis to break the hydrogen bonds between base pairs and open the fork.
152. Front

     Replication: which enzyme lays down the short RNA primer that DNA polymerase needs to start?
     Back

     Primase — it is an RNA polymerase that makes a ~10-nt RNA primer providing the free 3'-OH. (In eukaryotes the primase subunit of DNA pol α .)
153. Front

     Replication: which enzyme synthesizes the new strand, and in which direction?
     Back

     DNA polymerase — adds nucleotides only 5'→3' (reading template 3'→5'). It cannot start de novo — needs a primer with a free 3'-OH.
154. Front

     Which exonuclease activity does DNA polymerase use to proofread , and which direction does it run?
     Back

     Its 3'→5' exonuclease — backs up 3'→5', excises the mispaired nucleotide, and reinserts the correct one. Note: DNA pol α lacks this proofreading.
155. Front

     Replication: which enzyme seals the nicks between Okazaki fragments after primer removal?
     Back

     DNA ligase — forms the phosphodiester bond at the cost of ATP (eukaryotes) / NAD+ (bacteria). It joins pre-existing strands — it cannot synthesize DNA de novo.
156. Front

     Replication: which enzyme relieves the positive supercoils generated ahead of the fork?
     Back

     Topoisomerase — relaxes supercoiling . Type I cuts one strand; Type II cuts both strands (and can unlink catenanes).
157. Front

     Replication: which enzyme extends the chromosome ends to solve the end-replication problem?
     Back

     Telomerase — a reverse transcriptase carrying its own RNA template ; it extends the 3' end of the parental strand . Active in stem/cancer cells ; low/absent in most somatic cells .
158. Front

     Match the function → enzyme: seals nicks · unwinds helix · lays RNA primer · relieves supercoils
     Back

     seals nicks = ligase · unwinds = helicase · lays primer = primase · relieves supercoils = topoisomerase .
159. Front

     Replication TRAP: DNA polymerase needs a primer to start — but does RNA polymerase (transcription) need one?
     Back

     No — RNA polymerase needs NO primer. It can initiate synthesis de novo. Only DNA polymerase requires a primer (a free 3'-OH from primase ).
160. Front

     Which replication enzyme functions WITHOUT needing a pre-existing 3'-OH primer — DNA polymerase or primase/RNA polymerase?
     Back

     Primase / RNA polymerase — these synthesize RNA de novo , no primer required. DNA polymerase always needs a primer.
161. Front

     Translation: which ribosome site receives the incoming aminoacyl-tRNA ?
     Back

     The A site (aminoacyl site) — accepts each new incoming aminoacyl-tRNA (delivered by eEF1A, 1 GTP).
162. Front

     Translation: which ribosome site holds the peptidyl-tRNA (the tRNA carrying the growing chain)?
     Back

     The P site (peptidyl site) — holds the peptidyl-tRNA bearing the growing polypeptide.
163. Front

     Translation: which ribosome site is where the uncharged tRNA exits ?
     Back

     The E site (exit site) — the empty/uncharged tRNA leaves here after its amino acid has been transferred.
164. Front

     Match: incoming aminoacyl-tRNA · peptidyl-tRNA (growing chain) · uncharged tRNA exits → which ribosome site each?
     Back

     incoming aminoacyl-tRNA = A site · peptidyl-tRNA = P site · uncharged tRNA exits = E site . Ribosome moves 5'→3' along mRNA.
165. Front

     Translation: which activity forms the peptide bond , and what is it chemically made of?
     Back

     Peptidyl transferase — it is the rRNA of the large subunit , i.e. a ribozyme (not a protein). Eukaryote: 28S rRNA ; prokaryote: 23S rRNA .
166. Front

     Peptidyl transferase is a ribozyme — what does "ribozyme" mean here, and what does it catalyze?
     Back

     An RNA enzyme — the catalytic rRNA (28S/23S) of the large subunit catalyzes peptide bond formation between the A-site and P-site amino acids. The ribosomal proteins are scaffolding, not the catalyst .