Amino Acid Synthesis and 1-carbon Transfers Flashcards

1
Q

What are the six main amino acid metabolic families? What is this based on?

A

Glutamate, Serine, Aromatic, Aspartate, Pyruvate, Histidine

Each family is synthesized from the same raw material

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2
Q

What is the precursor for the glutamate family? What is the directly synthesized AA? What are the secondary AAs?

What are the reactions involved?

A

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.

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3
Q

Why is glutamine important?

A

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.

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4
Q

How is proline synthesized?

A

Derived from cyclization of side chain of glutamate.

Can also be synthesized from ornithine.

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5
Q

How is arginine synthesized?

A

Arginine is derived from glutamate–ornithine is an intermediate.

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6
Q

What is the precursor in the serine family? What are the primary and secondary AAs?

A

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.

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7
Q

How is glycine formed?

A

Remove side chain from serine–1 carbon removed and sent to THF pathway.

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8
Q

How is cysteine formed?

A

Carbon skeleton comes from serine, sulfur comes from dietary methionine.

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9
Q

What coenzyme is required for glycine and cysteine synthesis?

A

Pyridoxal phosphate

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10
Q

Why is serine important?

A

Precursor of ethanolamine and sphingosine

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11
Q

Why is glycine important?

A

Used to synthesize purines, porphyrins, glutathione

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12
Q

Why is cysteine important?

A

Sulfur metabolism

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13
Q

What is the precursor of the aspartate family? What are the primary and secondary and tertiary amino acids?

A

Precursor = oxaloacetate

Transaminated to form aspartate.

Asparagine, threonine, methionine, and lysine can be formed from aspartate.

Isoleucine can be formed from threonine.

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14
Q

How is asparagine synthesized?

A

Aspartate + glutamine -> asparagine + glutamate

Transfer of an amino group from glutamine to aspartate.

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15
Q

Why is aspartate important?

A

Source of nitrogen for urea formation
Source of oxaloacetate (CAC)
Source of nitrogen in nucleotide synthesis

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16
Q

What is the precursor in the pyruvate family? What are the primary AAs?

A

Pyruvate = precursor

AAs = isoleucine, alanine, valine, leucine

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17
Q

How is alanine synthesized?

A

Pyruvate + glutamate -> alanine + alpha-ketoglutarate

Amino group transfered from glutamate to pyruvate.

18
Q

What is the precursor of the histidine pathway? What is the primary AA?

A

Ribose-5-phosphate = precursor

Comes out of pentose phosphate pathway

Histidine is produced

19
Q

Is tyrosine an essential amino acid?

A

Sometimes–
Not an EAA if phenylalanine is available
Can’t make it from scratch

20
Q

How is tyrosine synthesized in the body? What is the coenzyme? Enzyme?

A

Phenylalanine -> Tyrosine
Coenzyme = BH4 (tetrahydrobiopterin) = cofactor in hydroxylation of aromatic amino acids
Enzyme = phenylalanine hydroxylase

First step in phenylalanine catabolism?

21
Q

What is tyrosine a precursor of?

A

Catecholamines [neurotransmitters] and melanin

22
Q

What is one-carbon metabolism? What are two one-carbon carriers? What are some one-carbon groups?

A

Transfer of one carbon atom from one molecule to another

Carriers = folic acid, s-adenosylmethionine (SAM)

Groups = methyl, methylene, formyl, methenyl

23
Q

What is folic acid? What is THF?

A

Folic acid = B vitamin
Converted into tetrahydrofolate (THF) by dihydrofolate reductase (DHFR)

Only THF is biologically active

24
Q

What is the THF pathway?

A

One carbon units become covalently bound to THF

25
Q

What is methotrexate?

A

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

26
Q

What is SAM? What does it do? What is SAM synthase?

A

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

27
Q

How do the THF and SAM cycles connect?

A

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

28
Q

How is glutathione produced?

A

Glutamate, cysteine, and glycine are linked.

2 ATP-dependent reactions.

29
Q

What are the functions of GSH?

A

Maintains proteins and enzymes in reduced state

Powerful antioxidant

Role in biochemical processes like DNA synthesis

30
Q

How does GSH eliminate toxins?

A

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

31
Q

What do excitatory neurotransmitters do?

A

Open sodium channels to depolarize membrane

32
Q

What do inhibitory neurotransmitters do?

A

Open chloride channels to hyperpolarize membrane?

33
Q

What AAs work as neurotransmitters?

A

Glycine, Glutamate, GABA

34
Q

What amines work as neurotransmitters

A

Epinephrine, norephinephrine, histamine, dopamine, etc.

35
Q

How is dopamine formed?

A

Tyrosine hydroxylated to form L-DOPA.
Coenzyme = BH4
Enzyme = tyrosine hydroxylase

L-DOPA is converted to dopamine

36
Q

How is norepinephrine formed?

A

Hydroxylation of dopamine

37
Q

How is epinephrine formed?

A

Norepinephrine is methylated (requires SAM) to form epinephrine

38
Q

How is GABA formed?

A

Decarboxylation of glutamate

GABA is an inhibitory neurotransmitter–low levels associated with epilepsy

39
Q

How is serotonin synthesized?

A

Synthesized from tryptophan in 2 reactions

1) Hydroxylation of tryptophan (BH4 is a coenzyme)
2) decarboxylation of hydroxylated tryptophan

40
Q

What is NO? How is it synthesized?

A

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

41
Q

How is histamine formed?

A

Decarboxylation of histidine

42
Q

How is heme synthesized?

A

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