Nucleotide Metabolism Lecture

Vocabulary flashcards covering major terms, enzymes, pathways, regulatory mechanisms, and clinical correlations from the nucleotide metabolism lecture.

Nucleotide

Molecule composed of a nitrogenous base, a pentose sugar, and one or more phosphate groups.

Nucleoside

Compound consisting of a nitrogenous base linked to a pentose sugar; lacks phosphate.

Nucleobase

Nitrogen-containing base (purine or pyrimidine) without sugar or phosphate.

Purine

Double-ring nitrogenous base family that includes adenine and guanine.

Pyrimidine

Single-ring nitrogenous base family that includes cytosine, thymine, and uracil.

5′-Phosphoribosyl-1-pyrophosphate (PRPP)

Activated ribose donor required for de novo and salvage synthesis of purine and pyrimidine nucleotides.

Glutamine-PRPP amidotransferase

Enzyme that catalyzes the committed, irreversible step of purine de novo synthesis—formation of 5-phosphoribosyl-1-amine.

Inosine 5′-monophosphate (IMP)

First purine nucleotide formed de novo; branch point precursor for AMP and GMP.

Adenylosuccinate synthetase

IMP-utilizing enzyme that begins AMP synthesis, driven by GTP.

IMP dehydrogenase

Enzyme that oxidizes IMP to XMP, initiating GMP synthesis; uses NAD⁺.

Feedback inhibition (purines)

End-product AMP, GMP, and IMP inhibit PRPP synthetase, glutamine-PRPP amidotransferase, and their own branch enzymes.

Reciprocal regulation

GTP drives AMP formation from IMP, whereas ATP drives GMP formation, balancing purine pools.

Pentose Phosphate Pathway

Metabolic pathway generating NADPH and ribose-5-phosphate, the sugar for nucleotide synthesis.

Carbamoyl phosphate synthetase II (CPS II)

Cytosolic enzyme that forms carbamoyl phosphate for pyrimidine de novo synthesis from glutamine, CO₂, and ATP.

Aspartate transcarbamoylase (ATCase)

Enzyme that catalyzes the committed step of pyrimidine synthesis, forming N-carbamoylaspartate; inhibited by CTP and activated by ATP.

Dihydroorotate dehydrogenase

Mitochondrial enzyme that oxidizes dihydroorotate to orotate during pyrimidine biosynthesis.

Orotidylate (OMP)

Orotate attached to PRPP; decarboxylated to UMP.

UMP/CMP kinase

Monophosphate kinase that converts UMP or CMP to their diphosphates using ATP.

Nucleoside diphosphate kinase (NDPK)

Broad-specificity enzyme that transfers phosphate from ATP to any nucleoside diphosphate to create NTPs.

Ribonucleotide reductase

Enzyme that converts ribonucleoside diphosphates (ADP, GDP, CDP, UDP) to deoxyribonucleotides; inhibited by hydroxyurea.

Thymidylate synthase

Enzyme that methylates dUMP to dTMP using N⁵,N¹⁰-methylene-THF as methyl donor.

dUTPase

Hydrolase that degrades dUTP to dUMP, preventing uracil incorporation into DNA.

5-Fluorouracil (FdUMP)

Suicide inhibitor that forms FdUMP, irreversibly blocking thymidylate synthase and dTMP production; used in cancer therapy.

Hydroxyurea

Drug that inhibits ribonucleotide reductase, lowering dNTP pools and slowing DNA synthesis; used in some cancers.

Adenine phosphoribosyltransferase (APRT)

Salvage enzyme that converts adenine + PRPP → AMP + PPᵢ.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Key salvage enzyme converting hypoxanthine or guanine + PRPP to IMP or GMP; deficiency causes Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome

X-linked disorder due to HGPRT deficiency; characterized by hyperuricemia, gout, neurobehavioral abnormalities, self-mutilation.

Gout

Disease caused by excess uric acid leading to sodium urate crystal deposition in joints; may result from overactive purine synthesis or impaired excretion.

Adenosine deaminase (ADA) deficiency

Immunodeficiency in which ADA loss leads to dATP accumulation, inhibition of ribonucleotide reductase, and failure of T and B cell development.

dATP (in ADA deficiency)

Elevated deoxynucleotide that inhibits ribonucleotide reductase, causing global dNTP shortage.

Xanthine oxidase

Enzyme that converts hypoxanthine → xanthine → uric acid during purine degradation.

Niacin (Vitamin B3)

Dietary vitamin or tryptophan derivative required to synthesize NAD⁺; deficiency causes pellagra.

Pellagra

Disease with dermatitis, diarrhea, and dementia resulting from niacin or tryptophan deficiency.

Nicotinamide adenine dinucleotide (NAD⁺)

Two-nucleotide coenzyme (AMP + nicotinamide mononucleotide) functioning in redox reactions.

Nicotinamide adenine dinucleotide phosphate (NADP⁺)

Phosphorylated derivative of NAD⁺ at 2′-OH of adenosine ribose; donor of reducing power for biosynthesis.

Flavin adenine dinucleotide (FAD)

Redox coenzyme synthesized from riboflavin (Vitamin B2) and AMP; carries electrons as FAD/FADH₂.

Riboflavin (Vitamin B2)

Precursor of FMN and FAD; deficiency leads to cheilosis (fissures at mouth corners).

Carbamoyl phosphate

Activated carbonyl donor formed by CPS II for pyrimidine biosynthesis.

Orotate phosphoribosyltransferase

Enzyme adding orotate to PRPP to form OMP.

CTP synthetase

UTP-dependent enzyme that converts UTP to CTP using glutamine as nitrogen donor.

Salvage pathway

Energy-saving process that recycles free bases/nucleosides into nucleotides using PRPP.

De novo pathway

Energy-costly synthesis of nucleotides from small metabolic precursors (CO₂, amino acids, NH₃, ribose-5-P, etc.).

Ribonucleotide

Nucleotide with ribose sugar (e.g., ATP, GTP).

Deoxyribonucleotide

Nucleotide with deoxyribose sugar (e.g., dATP, dGTP).

Wobble base (inosine)

Hypoxanthine-containing nucleotide in tRNA allowing pairing with multiple codons.

Hydrolysis vs. deamination

Key reactions in purine degradation: removal of phosphate (hydrolysis) and amine groups (deamination) produce xanthine.

Succinyl-CoA (pyrimidine breakdown)

Krebs cycle intermediate produced from thymine catabolism via β-aminoisobutyrate.

Ribonucleotide reductase regulation

Allosterically controlled by ATP (activator) and dATP (inhibitor) to balance deoxynucleotide pools.

PRPP synthetase

ATP-dependent enzyme forming PRPP from ribose-5-phosphate and ATP; feedback-inhibited by purine nucleotides.

DUTPase function

Protects DNA integrity by converting dUTP to dUMP, preventing uracil incorporation.