Purine and Pyrimidine Nucleotide Metabolism

A comprehensive set of practice flashcards covering the biochemistry of purine and pyrimidine nucleotides, including their structure, synthesis (de novo and salvage), catabolism, associated clinical disorders, and pharmacological inhibitors.

Nucleotide

A molecule composed of a sugar, a nitrogenous base, and a phosphate group.

Nucleoside

A molecule composed of a sugar and a nitrogenous base, lacking a phosphate group.

Purines

Nitrogenous bases featuring a double-ring structure (six-membered pyrimidine ring fused to a five-membered imidazole ring), including Adenine ($A$) and Guanine ($G$).

Pyrimidines

Nitrogenous bases featuring a single six-membered ring structure, including Cytosine ($C$), Thymine ($T$), and Uracil ($U$).

Complementary Base Pairing

The specific pairing of nitrogenous bases where Adenine pairs with Thymine (or Uracil in $RNA$) via $2$ hydrogen bonds, and Guanine pairs with Cytosine via $3$ hydrogen bonds.

Phosphodiester Bond

The bond that connects the $5'-OH$ group of one nucleotide to the $3'-OH$ group of another via a phosphate group, forming the backbone of $DNA$ and $RNA$.

Endonucleases

Enzymes that create adhesive ends by cutting phosphodiester bonds within the middle of a $DNA$ sequence.

Exonucleases

Enzymes that remove a single nucleotide from the terminal end of a $DNA$ chain.

Dactinomycin

A drug that enters the grooves of the $DNA$ double helix and disrupts $DNA$ synthesis.

DNA Helix Dimensions

A single turn of the double helix contains $10$ base pairs, covering a distance of $3.4\,nm$, with a helix width of $2\,nm$ and a distance between bases of $11\,Angstroms$. ($1\,nm = 10\,Angstroms$ or $10^{-9}\,m$).

Nucleosome

The structural unit of eukaryotic organization consisting of $DNA$ tightly bound to histone proteins ($Histone + DNA$).

Histones

Proteins rich in arginine and low in lysine that organize $DNA$; types include $H1$ (species-specific), $H2A$, $H2B$, $H3$, and $H4$.

Purine Ring Atom Origins

$N3$ and $N9$ from glutamine; $N1$ from aspartate; $N7$, $C4$, and $C5$ from glycine; $C2$ and $C8$ from tetrahydrofolate ($THF$); and $C6$ from $CO_2$.

PRPP (5-phosphoribosyl 1-pyrophosphate)

An active sugar intermediate required for both de novo and salvage pathways of nucleotide synthesis, formed from Ribose $5$-Phosphate and $ATP$ by $PRPP$ synthetase.

IMP (Inosine Monophosphate)

The first intermediate in de novo purine synthesis that contains a complete purine ring; it serves as the precursor for both $AMP$ and $GMP$.

Salvage Pathway

A process in which free purine bases (adenine, guanine, hypoxanthine) released from nucleic acid breakdown are recycled back into nucleotides using enzymes like $APRT$ and $HGPRT$.

Lesch-Nyhan Syndrome

An X-linked recessive disorder caused by a deficiency of the enzyme $HGPRT$, leading to hyperuricemia, neurological symptoms (self-mutilation, mental retardation), and increased de novo purine synthesis.

Uric Acid

The final product of purine catabolism in humans.

Xanthine Oxidase

The enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid, requiring $FAD$, iron ($Fe$), sulfur ($S$), and molybdenum ($Mo$) as cofactors.

Von Gierke Disease (Glycogen Storage Disease Type 1)

An autosomal recessive deficiency of glucose $6$-phosphatase that leads to an accumulation of Glucose $6$-phosphate, accelerating the pentose phosphate pathway and increasing purine synthesis, resulting in hyperuricemia.

Carbamoyl Phosphate Synthetase II (CPS II)

A cytosolic enzyme that catalyzes the rate-limiting step of de novo pyrimidine synthesis in eukaryotes ($Glutamine + CO_2 + 2ATP \rightarrow Carbamoyl\,phosphate$); inhibited by $UTP$ and activated by $ATP$ and $PRPP$.

Dihydroorotate Dehydrogenase

A mitochondrial enzyme that oxidizes dihydroorotate to orotic acid; distinct as most other pyrimidine synthesis enzymes are cytosolic.

Ribonucleotide Reductase

The rate-limiting enzyme that converts ribonucleotides to deoxyribonucleotides by reducing them at the $2'$ carbon; requires thioredoxin as a cofactor and is inhibited by hydroxyurea and $dATP$.

Thymidylate Synthase

The enzyme that converts $dUMP$ to $dTMP$ using $N5, N10$-methylene tetrahydrofolate as a methyl donor; inhibited by $5-fluorouracil$.

Orotic Aciduria

An autosomal recessive condition caused by a deficiency in orotate phosphoribosyl transferase or $OMP$ decarboxylase, characterized by growth retardation and severe megaloblastic anemia that does not respond to iron or B vitamins; treated with uridine or cytidine.

Beta-Alanine

The degradation product of the pyrimidines Cytosine and Uracil.

Beta-Aminoisobutyrate

The degradation product of the pyrimidine Thymine.