Nucleotides Flashcards
Metabolism of Xenobiotics: Phase 1 Reaction
Hydroxylation reactions
Enzyme: monooxygenases of cytochrome P450s
Medical compounds that are foreign to the body
Xenobiotics
Metabolism of Xenobiotics: Phase 2 Reaction
Conjugation reactions
Enzymes: Glucoronosyltransferases, sulfotransferases, glutathione S-transferases
The monomer units or building blocks of nucleic acids
Nucleotides
Nitrogen-containing heterocycles, cyclic compounds whose rings contain both carbon and other elements
Purines and Pyrimidines
Sugar + Purine or Pyrimidine; the link is a ring nitrogen
Nucleoside
Nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar
Nucleotides
5’-phosphoryl group forms a phosphodiester bond with the 3’-OH of another nucleotide; Pgosphodiesterases catalyze the hydrolysis of phosphodiester bonds
Polynucleotides
Purine ring is constructed by adding carbons and nitrogens to a preformed ribose-5-phosphate
Purine Synthesis
Purine Synthesis: Sources of atoms
Aspartic acid Glycine Glutamine Carbon dioxide N10-formyltetrahydrofolate and N5, N10-methenyltetrahydrofolate
In contrast, the pyrimidine ring is synthesized before being attached to ribose 5-phosphate
Pyrimidine Synthesis
Pyrimidine Synthesis: Sources of atoms
Glutamine
Aspartic acid
Carbon dioxide
What are the 2 compounds used in Purine Synthesis but not used in Pyrimidine Synthesis?
Glycine
N10-formyltetrahydrofolate and N5, N10-methenyltetrahydrofolate
An activated pentose that participates in the synthesis of purines and pyrimidines, and in the salvage of purine bases
Synthesis of 5-phosphoribosyl-1-pyrophosphate (PRPP)
Substrates: ATP and ribose 5-phosphate
Enzyme: PRPP synthetase
This is a committed step in purine nucleotide biosynthesis
Enzyme: glutamyl PRPP amidotransferase
Synthesis of 5’-phosphoribosylamine
9 steps that lead to the synthesis of IMP; “Parent” purine nucleotide
Synthesis of inosine monophosphate
Requires a two-step energy-requiring pathway; AMP synthesis requires GTP, while GMP synthesis requires ATP
Conversion of IMP to AMP and GMP
Purines that result from the normal turnover of cellular nucleic acids or that are obtained from the diet and not degraded, can be reconverted into nucleoside triphosphates and used by the body
Salvage Pathways for Purines
Salvage Pathways for Purines: Irreversible Enzymes
Adenine phosphoribosyltransferase (APRT) Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Steps in De Novo Pyrimidine Synthesis: Regulated and Rate limiting step
Enzyme: Carbamoyl phosphate synthetase II
Inhibited by UTP
Activated by ATP and PRPP
Synthesis of Carbamoyl phosphate
Steps in De Novo Pyrimidine Synthesis: Dihydroorotate reductase is located inside the mitochondria; All the rest are cystosolic
Synthesis of Orotic Acid
Steps in De Novo Pyrimidine Synthesis: The “parent” pyrimidine nucleotide is Orotidine monophosphate (OMP)
Formation of Pyrimidine nucleotide
Steps in De Novo Pyrimidine Synthesis: Enzyme: CTP synthetase
Synthesis of UTP and CTP
Steps in De Novo Pyrimidine Synthesis: Enzyme: Thymidylate synthase; N5N10-methyltetrahydrofolate is the source of the methyl group
Synthesis of dTMP from dUMP
Few pyrimidine bases are salvaged in human cells
Salvage Pathway for Pyrimidines
Nucleoside diphosphates are synthesized from the corresponding nucleoside monophosphates using base-specific nucleoside monophosphate kinases
Conversion of nucleoside monophosphate to nucleoside diphosphates and triphosphates
Enzyme: Ribonucleotide reductase;
It is multisubunit enzyme that is specific for the reduction of necleoside diphosphates to their deoxy forms
Synthesis of Deoxyribonucleosides
Degradation of dietary nucleic acids occurs in the small intestines where a family of pancreatic enzymes hydrolyze the nucleotides to nucleosides and free bases
Purine Degradation
The pyrimidine ring can be opened and degraded to highly soluble structures
Pyrimidine Degradation
Sulfonamides are structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid
PABA analogs
Methotrexate and TMP inhibit the reduction of dihydrofolate to tetrahydrofolate, catalyzed by dihydrofolate reductase
Folic Acid analogs
Hyperuricemia with recurrent attacks of acute arthritis caused by deposition of uric acid crystals
Gouty Arthritis
X-linked recessive deficiency in HGPRT that causes a rise in intracellular PRPP and hyperuricemia; triad of hyperuricemia, mental retardation, self-mutilation
Lesch-Nyhan Syndrome
Purine overproduction and hyperuricemia occurs secondary to enhanced generation of PRPP precursor ribose 5-phosphate
Von Gierke’s Disease
Leads to severe combined immunodeficiency (both T and B lymphocytes affected)
Adenosine deaminase deficiency
Metabolically converted to 5-FdUMP which becomes permanently bound to the inactivated thymidylate synthase
5-Fluorouracil
Low activities of orotidine phosphate decarboxylase and orotate phosphoribosyltransferase result in: Abnormal growth, megaloblastic anemia, excretion of large amounts of orotate in urine
Orotic Aciduria
Deoxyribonucleic acid; A polymer composed of nucleotide building blocks
DNA
5’-OH group attached to 3’-OH group; strands have directionality; bonds are cleaved hydrolytically by chemicals or hydrolyzed enzymatically by exonucleases or endonucleases
3’-5’ Phosphodieters bonds
Strands run in opposite directions
Antiparallel Strands
Held together by hydrogen bonds and hydrophobic interactions
Complementary base pairing
In any sample of dsDNA, the amount of adenine equals the amount of thymine, the amount of guanine equals the amount of cytosine
Chargaff’s Rules
Temperature at which one half of the helical structure is lost;
Under appropriate conditions, denaturation (annealing) may occur
Melting Temparature
Most common; Right-handed helix with 10 residues per 360 turn of the helix
B-DNA
Moderately dehydrated B form, also right-handed with about 11 base pairs per turn
A-DNA
Left-handed helix that contains about 12 base pairs per turn, naturally in regions of alternating purines and pyrimidines
Z-DNA
Five classes of small, positively charged proteins that form ionic bonds with negatively charged DNA
Histones
Further packing of DNA due to hydrophobic interactions and in association with other non-histone proteins compacts it into _____
Chromatin
Densely packed and transcriptionally inactive chromatin during interphase, observe by electron microscopy
Heterochromatin
Transcriptionally active chromatin that stains less densely
Euchromatin
Also called a nucleofilament; nucleosomes that are packed more tightly; Organized into loops that are anchored by a nuclear scaffold containing several proteins
Polynucleosome
Prokaryotic DNA Synthesis: Group of proteins that recognize the origin of replication
Step 1: DNA A protein
Prokaryotic DNA Synthesis: unwind the double helix ahead of the advancing replication fork
Step 2: Helicase
Prokaryotic DNA Synthesis: Maintain the separation of the parental strands
Step 3: Single-stranded DNA-binding proteins
Prokaryotic DNA Synthesis: Remove supercoils that interfere with the further unwinding of the double helix
Step 4: DNA topoisomerases