Chapter 32 - Metabolism of Nucleotides Flashcards
Which have more DNA and RNA: meats of fruits and veggies?
meat
While only __% of nucleosides absorbed are reutilized for nucleic acid synthesis, __% of these are used by rapidly regenerating enterocytes.
5, 25
nucleoside vs nucleotide
nucleotide contains 1 or more phosphate
deoxy-
one less oxygen
functions of nucleotides
- precursors of DNA and RNA
- ATP is an energy currency in biological systems
- adenine nucleotides are components of 3 major coenzymes (NAD, FAD, CoA
- activated intermediates in many biosynthetic pathways
- metabolic and physiological regulators
biosynthesis of purine nucleotides (A, G)
very little obtained from diet is used and most converted to uric acid which is secreted
-two pathways (de novo, salvage)
de novo pathway of purine nucleotides
precursors: Ribose 5-P, Aspartate, CO2, Gly, Gln, formate
5-Phosphoribosyl 1-pyrophosphate
PRPP; activated form of ribose 5-P
first committed step and point of regulation in de novo synthesis of purines is catalyzed by…
glutamine-PRPP amidotransferase
When making AMP, ____ is used
GTP
When making GMP, ____ is used.
ATP
AMP is formed by..
by the addition of aspartate followed by the release of fumarate.
GMP is formed by…
addition of water, dehydrogenation by NAD+, and the replacement of the carbonyl oxygen atom by
—NH2 derived by the hydrolysis of glutamine
During Purine nucleotide biosynthesis, what inhibits PRPP synthetase
ADP
During Purine nucleotide biosynthesis, what inhibits Gln-PRPP amidotransferase
AMP, GMP, IMP
During Purine nucleotide biosynthesis, what inhibits adenylosuccinate synthetase
AMP
During Purine nucleotide biosynthesis, what inhibits IMP dehydrogenase
GMP
Adenine phosphoribosyltransferase (APRT) catalyzes the formation of…
adenylate (AMP)
hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the formation of …
guanylate (GMP) as well as inosinate (IMP)
Which is major and which is minor: APRT or HGPRT?
minor: APRT (because most of the adenine is converted to hypoxanthine)
major: HGPRT
gout
characterized by high blood levels of
uric acid due to overproduction or
underexcretion of uric acid
gout treatments
grades, excretion stimulants, dietary and alcohol restrictions
Lesch Nyhan Syndrome
- deficiency in HGPRT activity due to mutations in the gene
- X linked and mostly affects males
Lesch Nyhan Syndrome consequence
The combination of increased synthesis, and decreased utilization, of purines leads to high levels of uric acid production
de novo pathway of pyrimidine nucleotides (U, C)
precursors: R5-P, CO2, Gln, Aspartate
- synthesize carbamoyl phosphate
- build pyrimidine ring (orotate)
- link orotate to R5P
synthesis of carbamoyl phosphate
- rate limiting step in pyrimidine synthesis
- carbamoyl phosphate synthetase II (CPSII)
CPS I vs CPS II: metabolic process
- urea synthesis
- pyrimidine nucleotide synthesis
CPS I vs CPS II: location
- mitochondrial matrix
- cytosol
CPS I vs CPS II: N donor
- NH4+
- Gln
CPS I vs CPS II: regulatory effectors
I: (+) N-acetylGlu, (+) Arginine
II: (-) UTP, (+) ATP, PRPP
5-phosphoribosyl-1-pyrophosphate
active form of ribose5P
-addition of pyrophosphate from ATP in a rxn catalyzed by PRPP synthetase
ribonucleotide reductase
reduction of ribonucleotides to deoxyribonucleotides
ultimate reductant
NADPH
chemotherapeutic agents
Inhibition of biosynthesis of DNA is a basis for some chemotherapies to slow up cell division (inhibition of thymidylate synthase and dihydrofolate reducatase)
inhibitors of thymidylate synthase
5-fluorouracil, Raltitrexed
inhibitors of dihydrofolate reductase
methotrexate (slows diwn psoriasis)
