PSB.339: L15–L16 Introduction to Nucleic Acids & Biosynthesis of Purines and Pyrimidines

Vocabulary terms and definitions covering nucleic acid chemistry, base structures, de novo and salvage nucleotide synthesis, folate pathway mechanisms, and associated pharmacological agents.

Nucleotide

A monomer unit of nucleic acids consisting of a nitrogenous base, a five-carbon sugar, and one or more phosphate groups.

Nucleoside

A compound composed of a nitrogenous base attached to a five-carbon sugar, lacking any phosphate group (for example, adenosine).

Ribose

The five-carbon sugar found in RNA that carries a hydroxyl group on the $2'$ carbon ($2'\text{-OH}$).

Deoxyribose

The five-carbon sugar found in DNA that carries only a hydrogen atom on the $2'$ carbon instead of an $-\text{OH}$ group.

Purines

A class of nitrogenous bases composed of two fused rings, comprising adenine (A) and guanine (G).

Pyrimidines

A class of nitrogenous bases composed of a single ring, comprising cytosine (C), thymine (T), and uracil (U).

Phosphodiester bond

The covalent linkage in a nucleic acid strand where a phosphate group connects the $3'$ carbon of one sugar to the $5'$ carbon of the adjacent sugar.

Antiparallel strands

The structural arrangement of the DNA double helix where the complementary strands run in opposite directions ($5' \rightarrow 3'$ opposite $3' \rightarrow 5'$).

Human genome

The complete collection of genetic instructions in human DNA, comprising approximately $3\,\text{billion}$ base pairs per set of $23$ chromosomes in the nucleus.

Chromatin

The complex formed when a single, very long DNA molecule is packaged and wrapped around histone proteins.

Gene

A specific segment of DNA that contains the instructions required to produce a functional RNA or protein.

De novo nucleotide synthesis

The biochemical pathway that constructs nucleotides step-by-step from smaller precursor molecules, consuming energy and utilizing multiple enzyme-catalyzed steps.

Nucleotide salvage pathway

The recycling pathway that produces nucleotides by recovering preformed nitrogenous bases and nucleosides, requiring less energy than de novo synthesis.

PRPP (5-phosphoribosyl-1-pyrophosphate)

An activated ribose compound formed from ribose-5-phosphate that serves as the sugar-phosphate scaffold onto which the purine ring is assembled.

IMP (inosine monophosphate)

The first fully formed purine nucleotide in de novo purine biosynthesis, which functions as the essential branch point leading to AMP and GMP.

Mycophenolic acid

An immunosuppressant drug used after organ transplantation that inhibits IMP dehydrogenase, blocking the conversion of IMP to GMP and inhibiting proliferation of T and B lymphocytes.

Orotate

A critical pyrimidine ring intermediate synthesized from glutamine, bicarbonate, and aspartate before attachment to PRPP in pyrimidine biosynthesis.

UMP (uridine monophosphate)

The first major pyrimidine nucleotide assembled during de novo pyrimidine synthesis, which serves as a precursor to UDP, UTP, and CTP.

Tetrahydrofolate (THF)

The active coenzyme form of folate (vitamin B9) that carries one-carbon units required for de novo purine synthesis and dTMP production.

Dihydrofolate reductase (DHFR)

An enzyme that uses NADPH to reduce dihydrofolate (DHF) back to tetrahydrofolate (THF), regenerating active folate cofactors for nucleotide synthesis.

Methotrexate

An antimetabolite drug that inhibits DHFR, preventing the regeneration of active folate and thereby impairing folate-dependent purine and dTMP synthesis.

Xanthine oxidase

The enzyme that catalyzes the final sequential oxidation reactions of purine breakdown, converting hypoxanthine to xanthine and xanthine to uric acid.

Uric acid

The final breakdown product of purine catabolism in humans (who lack the uricase enzyme), circulating predominantly as urate in body fluids.

Gout

An inflammatory arthritis triggered when high serum urate levels cause monosodium urate crystals to precipitate and deposit in joints and other tissues.

Allopurinol

A medication that inhibits xanthine oxidase to decrease uric acid production and lower serum urate levels over time.

Febuxostat

A xanthine oxidase inhibitor used for lowering urate levels that is contraindicated for co-administration with azathioprine or mercaptopurine.

Acyclovir

A guanosine nucleoside analog used for herpes simplex virus infections that is converted to a triphosphate and halts viral DNA elongation because it lacks a $3'\text{-OH}$ group.

5-Fluorouracil (5-FU)

A pyrimidine analog converted intracellularly into an active metabolite that inhibits thymidylate synthase, blocking dTMP production and impairing DNA synthesis.