Biochem Review: Eicosanoids, AAs, Urea Cycle, Special AA Products, FH4/B12/SAM, Purines & Pyrimidines

Flashcards covering core concepts from Eicosanoids, Amino Acid Synthesis/Degradation, Urea Cycle, Special AA Products, FH4/B12/SAM, and Purine & Pyrimidine metabolism.

What are the three main classes of eicosanoids?

Prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT).

What is the precursor for all eicosanoids?

Arachidonic acid (AA), a 20-carbon polyunsaturated fatty acid from linoleic acid.

Which enzyme releases arachidonic acid from membranes?

Phospholipase A2 (PLA2).

Which enzyme converts arachidonic acid into prostaglandins and thromboxanes?

Cyclooxygenase (COX).

Which enzyme converts arachidonic acid into leukotrienes?

Lipoxygenase.

Which enzyme produces epoxides and HETEs from arachidonic acid?

Cytochrome P450 epoxygenases/metabolizing enzymes.

What is the function of Thromboxane A2 (TXA2)?

Platelet aggregation and vasoconstriction (autocrine signal).

Which COX isoform is constitutive and protective in gastric mucosa?

COX-1.

Which COX isoform is inducible during inflammation?

COX-2.

Which COX isoform is a splice variant of COX-1?

COX-3.

How does aspirin affect COX enzymes?

Irreversibly acetylates COX, blocking PG/TX synthesis.

How do omega-6 and omega-3 fatty acids differ in eicosanoid production?

Omega-6 (AA) tends to produce pro-inflammatory series-2 PGs; omega-3 (EPA) produces anti-inflammatory series-3 PGs.

From which dietary sources are omega-6 and omega-3 eicosanoids derived?

Omega-6 from AA (linoleic acid pathway); omega-3 from EPA (from alpha-linolenic acid pathway).

In the fed state, what do amino acids primarily do?

Used for protein synthesis and neurotransmitter synthesis (insulin-driven).

In the fasting state, what happens to amino acids?

Muscle proteolysis releases alanine for gluconeogenesis in the liver.

In starvation, how are amino acids used?

Proteolysis slows; amino acids are used minimally for gluconeogenesis.

Which vitamin is required for transamination reactions?

Vitamin B6 (pyridoxal phosphate).

What is the difference between essential, nonessential, and conditionally essential amino acids?

Essential: must be obtained from diet; nonessential: body makes enough; conditionally essential: required in special conditions.

What are classical and malignant PKU due to?

Classical PKU: phenylalanine hydroxylase deficiency; malignant PKU: DHPR or BH4 synthesis defects.

What enzyme deficiencies cause cystathioninuria and homocystinuria (types I–III)?

Cystathioninase deficiency causes cystathioninuria; cystathionine β-synthase deficiency (B6-responsive) causes homocystinuria Type I; B12/folate metabolism defects cause Type II/III.

Which amino acids are exclusively ketogenic?

Leucine and lysine.

Which enzyme deficiency leads to hyperammonemia with orotic acid accumulation (OTC deficiency)?

Ornithine transcarbamoylase (OTC) deficiency.

What is a key effect of lead on heme synthesis?

Inhibition of δ-ALA dehydratase and ferrochelatase.

What bilirubin is direct (conjugated) bilirubin?

Direct bilirubin is water-soluble and conjugated with glucuronide.

What bilirubin is indirect (unconjugated)?

Indirect bilirubin is unconjugated and albumin-bound.

Which type of jaundice shows increased unconjugated bilirubin?

Hemolytic jaundice.

Which type of jaundice shows mixed bilirubin with increased urobilinogen?

Hepatocellular jaundice.

Which type of jaundice shows increased direct bilirubin, pale stools, and dark urine?

Obstructive jaundice.

What enzyme makes nitric oxide from arginine?

Nitric oxide synthase (NOS), requiring BH4.

What amino acid is a precursor to catecholamines?

Phenylalanine is converted to tyrosine, which is the precursor to catecholamines.

What amino acid is a precursor to GABA?

Glutamate.

What is the function of tetrahydrofolate (FH4)?

Carries 1-carbon units (methyl, methylene, formyl) for amino acid and nucleotide synthesis.

Which drug inhibits dihydrofolate reductase (DHFR)?

Methotrexate.

Which drug inhibits thymidylate synthase?

5-fluorouracil (5-FU).

How do sulfa drugs affect bacteria?

Block PABA to folate synthesis in bacteria.

Which deficiency causes spina bifida and megaloblastic anemia?

Folate deficiency.

What are the two main reactions of B12 (cobalamin) in metabolism?

Homocysteine → methionine (with FH4) and methylmalonyl-CoA → succinyl-CoA.

What are signs of B12 deficiency?

Macrocytic anemia and neurologic symptoms due to demyelination from methylmalonic acid accumulation.

What is SAM used for?

Methyl donor for creatine synthesis, norepinephrine to epinephrine, phospholipids, melatonin, and DNA methylation.

What are key precursors for purine nucleotide synthesis?

Ribose-5-phosphate, glutamine, glycine, aspartate, CO2, and FH4 one-carbon units.

What is the committed step of purine synthesis?

PRPP amidotransferase: PRPP → phosphoribosylamine.

How is purine synthesis regulated?

AMP and GMP feedback-inhibit PRPP amidotransferase and their own branch enzymes.

Which enzymes convert IMP to AMP and GMP?

IMP → AMP: adenylosuccinate synthetase and lyase; IMP → GMP: IMP dehydrogenase and GMP synthetase.

What is the purine salvage pathway enzyme?

HGPRT (hypoxanthine-guanine phosphoribosyltransferase).

What disease results from complete HGPRT deficiency?

Lesch-Nyhan syndrome (self-mutilation, hyperuricemia, gout).

Which enzyme deficiency causes SCID due to dATP inhibition of ribonucleotide reductase?

Adenosine deaminase (ADA) deficiency.

Which enzyme deficiency can cause gout from uric acid overproduction?

PRPP synthetase overactivity or HGPRT partial deficiency.

Which enzyme is inhibited by allopurinol in gout treatment?

Xanthine oxidase.

What enzyme reduces ribonucleotides to deoxyribonucleotides?

Ribonucleotide reductase.

How is ribonucleotide reductase regulated?

Inhibited by dATP; activated by ATP.

What is the committed step in pyrimidine synthesis?

CPS-II (carbamoyl phosphate synthetase II).

How is CPS-II regulated?

Activated by PRPP; inhibited by UTP.

Which enzyme links pyrimidine synthesis to DNA synthesis?

Thymidylate synthase (dUMP → dTMP; requires methylene-FH4).

What drug inhibits thymidylate synthase?

5-fluorouracil (5-FU).

Which enzyme inhibits DHFR, blocking dTMP synthesis?

Methotrexate.

What is orotic aciduria caused by?

UMP synthase deficiency; causes megaloblastic anemia with ↑orotic acid and no hyperammonemia.

How do you distinguish OTC deficiency from UMP synthase deficiency?

OTC: ↑orotic acid with hyperammonemia (urea cycle defect). UMP synthase deficiency: ↑orotic acid without hyperammonemia.

Which enzyme deficiency causes SCID with both B- and T-cell failure?

Adenosine deaminase (ADA) deficiency.

What nucleotide is required for dTMP synthesis?

dUMP.

Which nucleotide pathways are regulated by feedback inhibition?

Purines: AMP and GMP inhibit their own synthesis; Pyrimidines: UTP inhibits CPS-II.

Which CPS is used in the urea cycle?

CPS-I (mitochondrial, requires N-acetylglutamate as activator).

Which CPS is used in pyrimidine synthesis?

CPS-II (cytosolic, uses glutamine; not NAG).