Amino Acid Synthesis and 1-carbon Transfers Flashcards
What are the six main amino acid metabolic families? What is this based on?
Glutamate, Serine, Aromatic, Aspartate, Pyruvate, Histidine
Each family is synthesized from the same raw material
What is the precursor for the glutamate family? What is the directly synthesized AA? What are the secondary AAs?
What are the reactions involved?
Alpha-ketoglutarate is the precursor.
Transamination occurs to produce glutamate (primary).
Glutamate can then be converted to proline, arginine, glutamine.
To produce glutamine, glutamine synthetase adds an amino group to glutamate. Amino donor tends to be a branched-chain amino acid.
Why is glutamine important?
Amino group donor for many reactions.
Synthesis of purines and pyrimidines.
Synthesis of amino sugars–nitrogen donor.
Transport of NH4+.
Can be major source of energy.
How is proline synthesized?
Derived from cyclization of side chain of glutamate.
Can also be synthesized from ornithine.
How is arginine synthesized?
Arginine is derived from glutamate–ornithine is an intermediate.
What is the precursor in the serine family? What are the primary and secondary AAs?
Precursor = Glycerate-3-phosphate (glycolytic intermediate)
Reduced and transaminated to form phosphoserine.
Phosphate group removed to produce serine.
Serine can be converted into glycine and cysteine.
How is glycine formed?
Remove side chain from serine–1 carbon removed and sent to THF pathway.
How is cysteine formed?
Carbon skeleton comes from serine, sulfur comes from dietary methionine.
What coenzyme is required for glycine and cysteine synthesis?
Pyridoxal phosphate
Why is serine important?
Precursor of ethanolamine and sphingosine
Why is glycine important?
Used to synthesize purines, porphyrins, glutathione
Why is cysteine important?
Sulfur metabolism
What is the precursor of the aspartate family? What are the primary and secondary and tertiary amino acids?
Precursor = oxaloacetate
Transaminated to form aspartate.
Asparagine, threonine, methionine, and lysine can be formed from aspartate.
Isoleucine can be formed from threonine.
How is asparagine synthesized?
Aspartate + glutamine -> asparagine + glutamate
Transfer of an amino group from glutamine to aspartate.
Why is aspartate important?
Source of nitrogen for urea formation
Source of oxaloacetate (CAC)
Source of nitrogen in nucleotide synthesis
What is the precursor in the pyruvate family? What are the primary AAs?
Pyruvate = precursor
AAs = isoleucine, alanine, valine, leucine
How is alanine synthesized?
Pyruvate + glutamate -> alanine + alpha-ketoglutarate
Amino group transfered from glutamate to pyruvate.
What is the precursor of the histidine pathway? What is the primary AA?
Ribose-5-phosphate = precursor
Comes out of pentose phosphate pathway
Histidine is produced
Is tyrosine an essential amino acid?
Sometimes–
Not an EAA if phenylalanine is available
Can’t make it from scratch
How is tyrosine synthesized in the body? What is the coenzyme? Enzyme?
Phenylalanine -> Tyrosine
Coenzyme = BH4 (tetrahydrobiopterin) = cofactor in hydroxylation of aromatic amino acids
Enzyme = phenylalanine hydroxylase
First step in phenylalanine catabolism?
What is tyrosine a precursor of?
Catecholamines [neurotransmitters] and melanin
What is one-carbon metabolism? What are two one-carbon carriers? What are some one-carbon groups?
Transfer of one carbon atom from one molecule to another
Carriers = folic acid, s-adenosylmethionine (SAM)
Groups = methyl, methylene, formyl, methenyl
What is folic acid? What is THF?
Folic acid = B vitamin
Converted into tetrahydrofolate (THF) by dihydrofolate reductase (DHFR)
Only THF is biologically active
What is the THF pathway?
One carbon units become covalently bound to THF
What is methotrexate?
Methotrexate is a competitive inhibitor of dihydrofolate reductase?
1000x more affinity for DHFR than folic acid
Block generation of THF, block productions of nucleotide precursors for DNA
What is SAM? What does it do? What is SAM synthase?
S-adenosylmethioinine
Transfers methyl groups
SAM synthase covalently attaches methionine to sugar/purine of ATP.
Methyl transferases transfer the methyl group to different molecules.
Homocysteine must be released from SAH and must be converted to methionine for reuse.
SAM is methyl donor for >115 reactions
How do the THF and SAM cycles connect?
Methionie -> SAM -> SAH (s-adenosylhomocysteine) -> homocysteine -> methionine
Where does the carbon to convert homocysteine to methionine come from? Serine/glycine THF pathway
Serine -> glycine -> N5,N10-methylene THF -> N5-methyl THF
How is glutathione produced?
Glutamate, cysteine, and glycine are linked.
2 ATP-dependent reactions.
What are the functions of GSH?
Maintains proteins and enzymes in reduced state
Powerful antioxidant
Role in biochemical processes like DNA synthesis
How does GSH eliminate toxins?
Many toxins are water insoluble and difficult to excrete
GSH spontaneously conjugates to some toxins–can be catalyzed by GST-S transferase
Modification of conjugate yields a water soluble product
What do excitatory neurotransmitters do?
Open sodium channels to depolarize membrane
What do inhibitory neurotransmitters do?
Open chloride channels to hyperpolarize membrane?
What AAs work as neurotransmitters?
Glycine, Glutamate, GABA
What amines work as neurotransmitters
Epinephrine, norephinephrine, histamine, dopamine, etc.
How is dopamine formed?
Tyrosine hydroxylated to form L-DOPA.
Coenzyme = BH4
Enzyme = tyrosine hydroxylase
L-DOPA is converted to dopamine
How is norepinephrine formed?
Hydroxylation of dopamine
How is epinephrine formed?
Norepinephrine is methylated (requires SAM) to form epinephrine
How is GABA formed?
Decarboxylation of glutamate
GABA is an inhibitory neurotransmitter–low levels associated with epilepsy
How is serotonin synthesized?
Synthesized from tryptophan in 2 reactions
1) Hydroxylation of tryptophan (BH4 is a coenzyme)
2) decarboxylation of hydroxylated tryptophan
What is NO? How is it synthesized?
Nitric oxide–signaling molecule and neurotransmitter
- blood pressure regulation
NO synthesized by NO synthase
Arginine is substrate–2 step oxidation, to generate citrulline and NO
How is histamine formed?
Decarboxylation of histidine
How is heme synthesized?
Heme is iron containing porphyrin ring
Component of hemoglobin and myoglobin
In mammals–synthesized from 8 glyciine, 8 succinyl-CoA, and iron
Complex synthetic pathway
