Nucleotide Chemistry and Metabolism Flashcards

Which of the following nitrogenous bases is classified as a purine?

Answer: Adenine

Adenine and guanine are purines, characterized by a bicyclic structure of a pyrimidine ring fused to an imidazole ring, while cytosine, uracil, and thymine are monocyclic pyrimidines.

What distinguishes a nucleotide from a nucleoside?

Answer: Nucleotides contain one or more phosphate groups; nucleosides do not

A nucleotide consists of a nitrogenous base, a pentose sugar, and one or more phosphate groups, whereas a nucleoside contains only the base and the sugar without any phosphate.

In the DNA double helix, adenine forms hydrogen bonds with which complementary base?

Answer: Thymine

Adenine pairs with thymine in DNA via two hydrogen bonds (A=T), following Chargaff's rules, while guanine pairs with cytosine via three hydrogen bonds.

Which pyrimidine base is present in RNA but absent from DNA?

Answer: Uracil

Uracil replaces thymine in RNA; thymine contains a methyl group at C-5 that uracil lacks, and uracil pairs with adenine in RNA just as thymine does in DNA.

De novo purine nucleotide synthesis begins with which metabolite as the core scaffold?

Answer: Ribose-5-phosphate

De novo purine synthesis starts with ribose-5-phosphate (from the pentose phosphate pathway), which is converted to PRPP (5-phosphoribosyl-1-pyrophosphate), the activated ribose donor for ring assembly.

Lesch-Nyhan syndrome results from a deficiency of which enzyme in purine metabolism?

Answer: Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

HGPRT deficiency impairs the purine salvage pathway, leading to massive uric acid overproduction, causing gout, intellectual disability, and self-mutilating behavior characteristic of Lesch-Nyhan syndrome.

What is the final end product of purine catabolism in humans?

Answer: Uric acid

Humans lack uricase and therefore cannot convert uric acid to allantoin as most other mammals do; uric acid is thus the terminal product of purine breakdown, and its accumulation causes gout.

Which enzyme catalyzes the committed (first unique) step of pyrimidine biosynthesis?

Answer: Aspartate transcarbamoylase (ATCase)

ATCase (aspartate transcarbamoylase) catalyzes the condensation of carbamoyl phosphate with aspartate, forming carbamoyl aspartate, which is the committed step unique to pyrimidine biosynthesis.

Which nucleotide intermediate serves as the branch point from which both AMP and GMP are synthesized in the purine de novo pathway?

Answer: IMP (inosine monophosphate)

IMP is the first complete purine nucleotide formed in de novo synthesis and serves as the branch-point intermediate from which AMP and GMP diverge via separate enzymatic routes.

PRPP (5-phosphoribosyl-1-pyrophosphate) is best described as which of the following?

Answer: An activated ribose donor used in both de novo synthesis and salvage pathways

PRPP donates the activated ribose-5-phosphate moiety in both de novo nucleotide synthesis and salvage pathways for purines (HGPRT, APRT) and pyrimidines (OPRT).

Orotic aciduria type I is caused by a deficiency of which bifunctional enzyme?

Answer: UMP synthase (UMPS)

UMP synthase possesses both orotate phosphoribosyltransferase and OMP decarboxylase activities; its deficiency blocks the last two steps of pyrimidine synthesis, causing orotic acid accumulation and megaloblastic anemia.

5-Fluorouracil (5-FU) exerts its anticancer activity primarily by inhibiting which enzyme?

Answer: Thymidylate synthase

5-FU is converted to 5-FdUMP, which forms a covalent ternary complex with thymidylate synthase and N5,N10-methyleneTHF, irreversibly blocking dTMP synthesis and depleting the thymidine pool for DNA replication.

PRPP amidotransferase, which catalyzes the first committed step of de novo purine synthesis, is allosterically inhibited by which molecules?

Answer: AMP, ADP, ATP, GMP, GDP, and GTP

PRPP amidotransferase is subject to cumulative feedback inhibition by the end-product purine nucleotides (AMP/ADP/ATP and GMP/GDP/GTP), ensuring synthesis shuts down when purine pools are replete.

In the pyrimidine salvage pathway, uridine is converted directly to UMP by which enzyme?

Answer: Uridine kinase

Uridine kinase phosphorylates uridine (using ATP) to produce UMP in the salvage pathway, allowing cells to recycle preformed pyrimidine nucleosides without de novo synthesis.

Methotrexate inhibits nucleotide synthesis by targeting which enzyme?

Answer: Dihydrofolate reductase (DHFR)

Methotrexate competitively inhibits DHFR, preventing reduction of dihydrofolate to tetrahydrofolate; without THF cofactors, one-carbon transfer reactions required for both purine ring synthesis and dTMP formation are blocked.

Adenosine deaminase (ADA) deficiency causes which clinical condition, and why?

Answer: Severe combined immunodeficiency (SCID), due to toxic dATP accumulation in lymphocytes

ADA deficiency allows deoxyadenosine to accumulate and be phosphorylated to dATP, which is selectively toxic to lymphocytes (inhibits ribonucleotide reductase and induces apoptosis), resulting in SCID.

Allopurinol treats hyperuricemia and gout by inhibiting which enzyme?

Answer: Xanthine oxidase

Allopurinol (and its oxidized form oxipurinol) inhibits xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid, thereby lowering serum urate levels.

Cyclic AMP (cAMP) functions as a second messenger primarily by activating which intracellular target?

Answer: Protein kinase A (PKA)

cAMP binds to the regulatory subunits of protein kinase A, causing their dissociation and releasing active catalytic subunits that phosphorylate serine/threonine residues on downstream target proteins.

Ribonucleotide reductase reduces ribonucleotides to deoxyribonucleotides using which catalytic mechanism?

Answer: A stable tyrosyl radical stabilized by a dinuclear iron center

Ribonucleotide reductase class I uses a stable tyrosyl radical (generated by a diferric iron center in the R2 subunit) to initiate the radical-based mechanism that removes the 2'-OH of ribonucleotides.

NAD+ is synthesized in cells using which vitamin as the key precursor of the nicotinamide ring?

Answer: Niacin (B3)

Niacin (vitamin B3), supplied as nicotinic acid or nicotinamide, provides the nicotinamide moiety of NAD+ and NADP+; deficiency causes pellagra and impairs all NAD+-dependent redox reactions.