Biochem- Nuleotide Metabolism I & II Flashcards
What are the two types of pathways used in Nucleotide Synthesis?
- De novo synthesis — Uses metabolic precursors.
- Salvage pathways — uses free bases and nucleosides release from nucleotide breakdowns (turnover)
What is the major site of purine synthesis (de nova and salvage pathways)?
Liver.
What does Purine De Novo synthesis begin with?
The synthesis of 5-phosphoribosyl 1- pyrophosphate (PRPP).
Note: Also common to pyrimidine synthesis.
State the first 5 steps of De Novo Synthesis.
- Ribose-5- phosphate — PRPP synthase — PRPP.
- PRPP — PRPP Glutamyl Amidotransferase — 5-phosphoribosylamine
- 5-phosphoribosylamine — phosphoribosylglycinamide synthetase — Glycinamide-ribosyl-5-phosphate. (3 atoms from glycine)
- Glycinamide r-5-p — Formyltransferase — formyglycinamide r-5-p
- Formyglycinamide r-5-p — vi synthetase — Formyglycinamidine r-5-p.
Discuss steps 6-11 of De Novo Synthesis.
- Formylglycinamidine r-5-p — VII Synthetase — Aminoimidazole r-5-p
- Aminoimidazole r-5-p — VII carboxylase — Aminoimidazole carboxylate r-5-p
- Aminoimidazole carboxylate r-5-p — IX Synthetase — Aminoimidazole succinate carboxamide r-5-p
- Aminoimidazole succinate carboxamide r-5-p — adenylosuccinase — Aminoimidazole carboxamide r-5-p
- Aminoimidazole carboxamide r-5-p — Formimidoimidazole carboxamide r-5-p
- Formimidoimidazole carboxamide r-5p — IMP Cyclohydratase — Inosine monophosohate IMP
List the two compounds IMP can be converted to.
Adenylate (AMP)
Guanylate (GMP)
State the formation of AMP from IMP
IMP —adenylosuccinate synthase— adenylosuccinate — adenylosuccinate lyase — AMP
State the formation of GMP from IMP
IMP - IMP dehydrogenase— xanthylate — XMP glutamine amidotransferase — GMP
Nucleoside monophosphate is catalyzed to diphosphates via?
A base specific nucleoside monophosphate kinases.
AMP + ATP = 2ADP
GMP + ATP = GDP + ADP
Nucleoside diphosphate is converted to nucleotides by?
A broad specific nucluesode diphosphate kinase.
GDP + ATP = GTP + ADP
State the regulation of Purine De Novo Synthesis.
- The synthesis of PRPP.
- Rate limiting enzyme - PRPP synthase.
What inhibits PRPP synthase?
AMP
ADP
GMP
GDP
What is glutamine- PRPP- amidotransferase inhibit by?
AMP
GMP
IMP
What does AMP and GMP feedback inhibit?
AMP — adenylosuccinate synthase
GMP — IMP dehydrogenase
List the 3 bases form in purine salvage rxns.
Adenine
Guanine
Hypoxanthine
List the enzymes involves in the salvage reactions of adenine, hypoxanthine and guanine.
Adenine — adenine phosphoribosyltransferase
Hypoxanthine — hypoxanthine -guanine phosphoribosyltransferase.
Guanine - HGPRT
State the compounds need for the reduction of deoxynucleotides.
Thioredoxin
Thioredoxin reductase
NADPH
Enzyme involved: ribonucleotide reductase complex
Describe the Purine degradation of AMP.
- AMP
- Adenosine — Inosine ( adenosine deaminase)
- Inosine — hypoxanthine (nucleosidase)
- Hypoxanthine — xanthine (xanthine oxidase)
Describe the Purine degradation of GMP.
1.GMP — Guanosine
2. Guanosine — Guanine (nucleosidase)
3. Guanine — xanthine (guanosine deaminase)
What is the end product for the oxidation of Xanthine?
Xanthine — uric acid
Note- uric acid is common in primates, birds and some animals.
What are the disorders of Purine metabolism?
- Gout
- Lesch- Nyhan Syndrome
- Hypouricemia - (xanthine oxidase deficiency)
- Adenosine deaminase deficiency (T and B lymphocytes)
- Purine nucleoside phosphorylase deficiency (T cells affected)
Give some characteristics about Gout.
- elevated concentrations of uric acid
- Abnormal deposition of sodium urate crystals.
- Seen more in males
- Underexcretion of urate
- Genetic defects in PRPP synthase.
State the treatment for Gout.
- Low diet in nucleic acids
- Allopurinol (inhibits xanthine oxidase)
Give some characteristics about Lesch-Nyhan Syndrome.
- Hyperuricema
- Deficiency of HGPRT
- Excessive uric acid
