Nucleotide Metabolism (Week 14)

Nucleotide

5-carbon sugar, nitrogenous base, and phosphate group

Nucleoside

5-carbon sugar, and a nitrogenous base, no phosphate group

Pentose pathway

Where pentose sugar comes from in nucleotide/nucleoside formation via G6PD

A, G

Purines

C, T, U

Pyrimidines

Purines, pyrimidines, de novo

__ and __ are required for synthesizing nucleotides and nucleic acids via __ __

ATP

Important biomolecule is byproduct of purine formation

PRPP synthetase

Key enzyme converting Ribose 5-P to this product… (for nucleotide synthesis)

De novo synthesis

Purines and pyrimidines are synthesized from smaller precursors, and PRPP is added to the pathway

Salvage pathways

Preformed purine and pyrimidine bases can be converted into nucleotides by enzymes

Carbamoyl phosphate synthetase 2 (CSP2)

Enzyme for pyrimidine synthesis de novo in cytoplasm, regulated step

Aspartate, CO2, glutamine

Pyrimidines are synthesized de novo in cytoplasm from - (3)

Dihydrofolate reductase, antineoplastic, methotrexate

__ (enzyme) initiates production of THF from conversion of UMP to dTMP

• Target of __ drugs

  • Drug target is specifically __

Decrease, UTP, CPSII

As pyrimidines __ in concentration (as indicated by __ levels), __ (enzyme) is activated and pyrimidines are synthesized

PRPP amidotransferase

Catalyzes first and rate-limiting reaction of de novo purine synthesis in liver

Allopurinol

Inhibits xanthine oxidase and also can reduce purine synthesis

PRPP amidotransferase, HGPRT

Allopurinol reduces purine synthesis by inhibiting __ __ (enzyme), if __ is active

PRPP synthetase, PRPP amidotransferase

• Rate-limiting enzyme for pyrimidine synthesis = __ __

• Rate-limiting enzyme for purine synthesis = __ __

HGPRT

Transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate

purine salvage

HGPRT plays a central role in the generation of purine nucleotides through the __ __ pathway

Hypoxanthine, guanine, xanthine

(3) - Molecules either salvaged or excreted via Purine catabolism

Uric acid

End product of dietary purines from catabolism, after Xanthine, hypoxanthine, guanine

Gout

Too much Xanthine, guanine, hypoxanthine (uric acid) formation from excess xanthine oxidase

Allopurinol

Inhibits excretion pathway activity of xanthine oxidase for therapeutic relief

Other metabolic waste, flare ups

Exercising with gout is counter-intuitive due to the production of __ __ __ along with uric acid

• Means less is cleared out and can lead to __ __

Lesch-Nyhan Syndrome

Excess excreted Xanthine, guanine, hypoxanthine (uric acid) from deficient HGPRT

X-linked recessive

Lesch-Nyhan Syndrome and Gout Inheritance Pattern

Lesch-Nyhan Syndrome sx

Mental retardation, spastic cerebral palsy with compulsive biting of hands and lips, hyperuricemia, death in 1st decade

Gout sx

Severe pain, redness, and swelling in joints; monosodium urate crystals

Orotic Aciduria

Defective OTC enzyme where carbamoyl-P accumulates in mitochondria, leaks out into cytoplasm, high OTC