Purines/Pyrimidines, AA Synthesis and Metabolism, Catecholamines Flashcards
First step of purine synthesis
Ribose 5 Phosphate (pentose phosphate pathway) comes 5-phosphoribosyl-1-pyrophosphate (PRPP) using ATP via PRPP synthetase. Inhibited by IMP, GMP, AMP.
Amidophosphoribosyl transferase reaction
Second step of purine synthesis, also the rate limiting step. PRPP + Glutamine –> 5 phosphoribosylamine via amidophosphoribosyl transferase. 5 Phosphoribosylamine becomes Inosine monophosphate eventually (which has hypoxanthine as its base). Inhibited by IMP, AMP, and GMP.
AMP Synthesis
IMP + Aspartate +GTP –> Adenosuccinate –> AMP + Fumarate. This reaction is inhibited by AMP.
GMP Synthesis
IMP + NAD –> Xanthylate
Xanthylate + Glutamine + ATP –> GMP + Glutamate. This reaction is inhibited by GMP.
How do XMP’s become XDP’s?
Easily, utilizing nucleoside monophosphate kinase.
How do XDP’s become XTP’s?
Easily, utilizing nucleoside diphosphate kinase.
Salvage Pathway Purpose
When purines are degraded to free bases, they can be salvaged rather than excreted.
Salvage Pathway for A
Adenine + PRPP —> AMP + PPi Via Adenine phosphoribosyl transferase
Salvage Pathway for G/Xanthine
Guanine/Hypoxanthine + PRPP –> GMP/IMP + PPi via hypoxanthine/guanine phosphoribosyl transferase.
Lesch-Nyhan Syndrome
HGPRT deficiency
Purine Metabolism
Guanine –> Xanthine –> Uric Acid
Adenine –> Hypoxanthine –> Xanthine –> Uric acid
Purpose of Uric Acid
To neutralize ROS in blood
Gout
Uric Acid Crystals cause inflammation
Pyrimidine Synthesis First Step
Glutamine + CO2 –> Carbamoyl Phosphate via CPS II
CPS II and reaction
Found in the cyto of all cells, not only in liver mitochondria like CPS I. Not increased by NAGA.
Glutamine + CO2 –> Carbamoyl Phosphate
Rate Limiting Step of Pyrimidine Synthesis
Carbamoyl Phosphate + Aspartate –> N-Carbamoyl Aspartate (via Aspartate Transcarbamoylase)
N-Carbamoyl Aspartate
Makes UMP, which makes UDP, which makes UTP
How does UTP become CTP?
UTP + Glutamine –> CTP + Glutamate
Orotate
Intermediate in pyrimidine synthesis. Accumulates in people with Ornithine Transcarbamylase deficiency.
Deoxyribose Formation
Ribose –> Deoxyribose, but not the other way around. Occurs via ribonucleotide reductase.
Ribonucleotide Reductase Structure
B1 has overall activity site and specificity site. B2 has catalytic site with tyrosines and thiols
How does RR work?
Using a tyrosine to create a radical. Thiols will be oxidized, then reduced by thioredoxin, thioredoxin reductase, FADH2, NADPH.
How is RR regulated at the overall activity site?
Increased activity by ATP, shut down by dATP.
C3 Family of AA’s
Alanine, Tryptophan (becomes Alanine and acetyl CoA), Glycine, and Cysteine
How is RR regulated at the specificity site?
ATP generates d Pyrimidines. dTTP decreases pyrimidines and increases dGTP synthesis. dGTP causes dATP generation, which shuts down the mechanism.
Alanine Metabolism
Alanine + AKG –> Pyr + Glu via GPT
Glycine Metabolism
Glycine–> Serine (Via Serine Transhydroxymethylase)
Serine –> Pyruvate
Cysteine Metabolism
Cysteine –> Pyruvate + S
C4 Family of AA’s
Aspartate, Asparagine, Methionine, Valine, Threonine, Isoleucine
Aspartate Metabolism
Aspartate + AKG –> Glutamate + OAA via GOT
Asparagine Metabolism
Asparagine –> Aspartate + NH3 via Asparaginase
Methionine, Valine, Threonine, Isoleucine Metabolism
Become propionyl CoA –> Methylmalonyl CoA –> Succinyl CoA
C5 family of AAs
Glutamate, Glutamine, Histidine, Arginine
Glutamate Metabolism
Glu + NAD –> AKG + NH3
Glutamine Metabolism
Glutamine –> Glutamate + NH3 via Glutaminase
Histidine Metabolism
Histidine become formamino glutamine, which becomes formamino THF
Arginine Metabolism
Arginine –> Urea + Ornithine via Arginase
BCAAs and their metabolism
Valine, Isoleucine, Leucine undergo transamination with AKG to form their respective alpha ketoacid. This is then decarboxylated by BCAlphaKetoacid Dehydrogenase to create CoA and CO2. This second reaction uses a E3 mechanism like pyruvate dehydrogenase.
Phenylalanine Metabolism
Phenylalanine + Tetrahydrobiopterin + O2 –> Tyrosine via Phenylalanine Hydroxylase
PKU
Caused by a deficiency in Phenylalanine Hydroxylase
Tyrosine Metabolism
Tyr –> Fumarate and Acetoacetate
Mixed Function Oxidation
Where the atoms of an O2 are split up into different products.
Catecholamine Synthesis
Occurs in adrenals. Tyrosine –> DOPA (Via tyrosine hydroxylase and THB) –> Dopamine (via DOPA decarboxylase) –> NE (Via DA Betahydroxylase) –> Epi (Via SAM methyltransferase)
5-HT Synthesis
Tryptophan –> 5HTP (Via Tryptophan Hydroxylase + THB) –> 5-HT (via DOPA decarboxylase) –> NAcetylSerotonin –> Melatonin
What three amino acids make up Glutathione?
Glutamate, Cystine, Glycine
