Nucleotide and deoxynucleotide metabolims- Lecture 77-78 Flashcards
(33 cards)
What are the functions of purines and pyrimidines?
active precursors of DNA and RNA activated intermediates in carb (UDP) and lipid (CDP) metabolism, and methylation (SAM) high energy intermediates metabolic regulators part coenzymes
What is the structure of a nucleoside?
base + sugar
What is the structure of a nucleotide?
nucleoside + Pi
How is the activated form of ribose synthesized?
ribsose 5-P + ATP –> 5-phosphoribosyl-1-pyrophosphate (PRPP) + ADP
via PRPP synthase (ribose P pyrophosphokinase)
Describe the second step of purine ring synthesis.
PRPP + glutamine –> 5-Phosphoribosyl-1-amine + glutamate
via amido phosphoribosyl transferase
rate limiting
Describe the final steps of purine ring synthesis.
IMP + GTP + Asp –> GDP + adenylosuccinate
adenylosuccinate –> adenylate (AMP) + fumarate
OR
IMP + NAD+ –> xanthylate + NADH
xanthylate + Gln + ATP –> guanylate (GMP) + Glu + AMP
What is the composition of a purine ring?
N1 from Asp C2 from N10 formyl THF C8 from N5,N10 methenyl-THF C4, C5, N7 from Glycine C6 from CO2 N3, N9 from Glutamine
Where does purine ring synthesis occur?
in the cytosol of all cells
What regulates purine synthesis?
AMP inhibits step 1
GMP inhibits step 2
Describe the process of nucleoside phosphate interconversion.
Any XMP –> XDP via nucleoside mono P kinase + XTP
(GMP + ATP < —- > GDP + ADP)
(CMP + GTP < —- > CDP + GDP)
Any XDP –> XTP via nucleoside di P kinase + XTP
(GDP + ATP < —- > GTP + ADP)
(CDP + GTP < —- > CTP + GDP)
What are the fates of RNA degraded into free nitrogenous bases?
excreted as uric acid
salvaged and returned to the purine nucleotide pool
Why is the purine salvage pathway important?
because purines that are salvaged don’t need to be synthesized by energetically expensive de novo pathways
What are the two major purine salvage enzymes?
adenine phosphoribosyl transferase (APRT)
hypoxanthine guanine phosphoribosyl transferase (HGPRT)
What is the function of adenine phosphoribosyl transferase (APRT)?
adds PRPP to adenine to make AMP
What is the function of hypoxanthine guanine phosphoribosyl transferase (HGPRT)?
adds PRPP to guanine or hypoxanthine to make GMP or IMP
What is Lesch-Nyhan syndrome?
deficiency of HGPRT resulting in compulsive self-mutilation, aggressiveness, spacisticity, intellectual disability
Describe the breakdown of GMP.
GMP –> guanosine –> guanine –> xanthine –> uruic acid
via xanthine oxidase
excretion in urine
Describe the breakdown of AMP.
AMP --> IMP via adenosine deaminase IMP --> inosine --> hypoxanthine --> xanthine via xanthine dehydrogenase xanthine --> uric acid via xanthine oxidase excretion in urine
What is gout?
excess uric acid produces crystalline, insoluble deposits of calcium and urate in the joints –> pain and inflammation
associated with high purine diet, alcohol, renal disease, deficiencies in salvage enzymes, and ketoacidosis
How do you treat gout?
low purine diet
ant-inflammatory agents (eg methotrexate/colchicine) decrease immune cell proliferation
allopurinol (suicide inhibitor of XDH/XO, buildup hypoxanthine, more soluble than uric acid)
Describe the pathway of pyrimidine biosynthesis.
- glutamine + CO2 + 2ATP –> Carbamoyl phosphate
via carbamyl synthase II (CPSII) - Asp + carbamoyl phosphate –> N-carbamoylaspartate + Pi
via aspartate transcarbamylase
Carbamoylaspartate –> –> –> orotate + PRPP –> CO2 + UMP
UMP –> UDP –> UTP
via nucleoside mono-/di-phosphate transferase
What regulates the pyrimidine biosynthesis pathway?
product inhibition (UTP inhibits step 1 and CTP inhibits 2nd step)
High levels of orotic acid in blood can be due to _________.
decrease in the urea cycle enzyme ornithine transcarbamylase
There are _____ reactions by which a deoxynucleotide can be converted to ribonucleotide, however, a ribonucleotide can be converted to deoxynycleotide by _______.
no
ribonucleotide reductase
