The Synthesis and Degradation of Nucleotides

Practice flashcards covering nucleotide structure, biosynthesis of purines and pyrimidines, related metabolic diseases, and drug interactions as detailed in the lecture transcript.

Nucleotide

A metabolic building block composed of a heterocyclic base, a pentose sugar, and a phosphate group.

$\beta$-glycosidic linkage

The specific bond connecting the $N-1$ of a pyrimidine or the $N-9$ of a purine to the $C-1$ of a pentose sugar in a nucleoside or nucleotide.

Tetrahydrofolic acid (THF)

A derivative of folic acid that acts as a carrier for one-carbon (C-1) units such as methanol, formaldehyde, and formic acid.

PABA (p-aminobenzoic acid)

An important precursor in folic acid synthesis; its competitive inhibition by sulfonamides or sulfa drugs blocks folic acid formation in bacteria.

$N^5$-methyl THF

The specific derivative of tetrahydrofolate that acts as the methyl group donor in the biosynthesis of methionine.

Serine hydroxymethyl transferase

The enzyme that uses serine as the principle source of one-carbon units, requiring a pyridoxal phosphate derivative and producing glycine and $N^5, N^{10}$-Methylene THF.

De Novo Pathway

A biosynthetic pathway that builds complex end products like purine or pyrimidine rings from scratch using simple precursors.

PRPP (5-Phosphoribosyl-$\alpha$-pyrophosphate)

The activated form of ribose-5-phosphate that serves as the starting point for both de novo and salvage pathways of nucleotide synthesis.

IMP (Inosine monophosphate)

The common purine precursor in the de novo pathway from which both adenosine-$5^{\prime}$-monophosphate (AMP) and guanosine-$5^{\prime}$-monophosphate (GMP) are synthesized.

Azaserine

An irreversible inhibitor of glutamine-dependent enzymes used as an antitumor or immunosuppressive agent in the purine synthesis pathway.

Methotrexate

A folic acid antagonist that binds to dihydrofolate reductase with approximately $1000$-fold greater affinity than DHF, blocking the regeneration of THF.

HGPRT

Hypoxanthine-Guanine Phosphoribosyltransferase, a salvage enzyme that re-attaches purine rings to ribose; a genetic deficiency in this enzyme causes Lesch-Nyhan Syndrome.

Lesch-Nyhan Syndrome

A congenital, X-linked recessive trait characterized by excessive uric acid accumulation, gouty arthritis, mental retardation, and aggressive self-mutilation behaviour.

Xanthine Oxidase

The enzyme that converts hypoxanthine and xanthine into uric acid; its inhibition by allopurinol is used to treat gout.

Gout

A condition characterized by painful joint inflammation due to an excess of uric acid and subsequent urate deposition in cartilaginous tissue.

AZT ($3^{\prime}$-azido-$2^{\prime}$-deoxythymidine)

A nucleoside derivative used to treat HIV/AIDS that acts as a DNA synthesis chain terminator by inhibiting reverse transcriptase.

SCID (Severe Combined Immunodeficiency Disease)

An inherited disease often caused by adenosine deaminase (ADA) deficiency, leading to high levels of dATP which inhibit deoxynucleotide synthesis and cell division in lymphocytes.

CPS-II (Carbamoyl Phosphate Synthetase II)

A cytosolic enzyme used for pyrimidine biosynthesis that utilizes $HCO_3^-$, glutamine, and $2\,ATP$ to form carbamoyl phosphate.

Metabolic Channeling

A process in multifunctional enzymes where the product of one reaction is handled directly as a substrate for the next active site without diffusing through the solution.

Ribonucleotide Reductase

The enzyme responsible for converting ribonucleoside diphosphates (NDPs) into $2^{\prime}$-deoxyribonucleoside diphosphates (dNDPs) via a free radical mechanism.

Thymidylate Synthase

The enzyme that catalyzes the synthesis of dTMP from dUMP using $N^5, N^{10}$-Methylene-THF as the methyl group donor.

5-Fluorouracil (5-FU)

An anti-cancer drug and thymine analog that is converted into $2^{\prime}$-deoxy-$5$-fluorouridylate to potently inhibit thymidylate synthase.

Leptin

A $16\,kDa$ protein produced by adipocytes that suppresses appetite, regulates fat metabolism, and stimulates thermogenesis by inducing uncoupling protein-$2$.

Ghrelin

A peptide hormone known as the hunger hormone that stimulates appetite, producing the opposite effect of leptin.