Amino Acid Biosynthesis

Plants and microbes synthesize all 20 amino acids

The amino group is derived from glutamate via transamination of the

corresponding α-keto acid

Mammals can sythesize only 10 of the 20 amino acids

Nonessential amino acids: those that can be synthesized

Essential amino acids: those that cannot be synthesized

Essential

ArginineHistidineIsoleucineLeucineLysine

MethioninePhenylalanine

ThreonineTryptophan

Valine

Nonessential

AlanineAsparagineAspartateCysteine

GlutamateGlutamine

GlycineProlineSerine

Tyrosine

Amino Acids are derived from intermediates in glycolysis; TCA cycle; pentose phosphate pathway

Amino acids are classified according to the source for their

corresponding α-keto acid

Glucose

Glucose-6-PO4

Ribose-5-PO4

Histidine

3-PGA Serine

PEP

Pyruvate

Erythrose-4-PO4

Tryptophan; Phenylalanine; Tyrosine

Glycine; Cysteine

Alanine; Valine; Leucine

Citrate

a-KgOAA

AspartateGlutamate

Asparagine; Methionine; Threonine; Lysine; Isoleucine

Glutamine; Proline; Arginine

α−Kg Family

GlutamateGlutamine

ProlineArginine

Lysine

Aspartate Family

AspartateAsparagineMethionineThreonineIsoleucine

Lysine

Pyruvate Family

AlanineValine

Leucine

3-Phosphoglycerate Family

Serine GlycineCysteine

PEP and Erythrose-4-P Family

PhenylalanineTyrosine

Tryptophan

Histidine is derived from PRPP (phosphoribosylpyrophosphate)

Transamination is one principle route by which amino acids are

synthesized from their corresponding α-keto acids

Predominant amino acid/α-keto acid pair is glutamate/α-Kg

a-Kg Family:

Proline is derived from glutamate in a series of 4 reactions that involves reduction of the carboxyl R group to an aldehyde which then spontaneously cyclizes.

Arginine biosynthesis involves steps that are part of the urea cycle and depends on the formation of ornithine. Ornithine has three metabolic roles: 1) as a precursor to arginine; 2) as an intermediate in the urea cycle; 3) as an intermediate in Arginine degradation.

-O-C-CH2-CH2-C-C-O-

O OH

NH3+

-O-C-CH2-CH2-C-C-O-

O OH

NH3+

O=PO-

O-

Glutamate 5-P

Glutamate 5-semialdehyde

H-C-CH2-CH2-C-C-O-

O OH

NH3+

Proline

Lysine biosynthesis in fungi stems from a-Kg; in other organisms it comes from

aspartate.

Starting from a-Kg, the carbon chain is lengthened by one Carbon in a series of steps

reminiscent of the TCA cycle:Acetyl CoA is condensed with a-Kg to form

homocitrate; homoisocitrate is formed; oxidative decarboxylation removed one carbon

leaving the intermediate a-ketoadipate; 5 additional steps then form lysine

C=OO-

CH2

CH2

C=OC=O

O-

α-Kg

C=OO-

CH2

CH2

C=OO-

HO-C-C=OO-CH2

Homocitrate

C=OO-

CH2

CH2

C=OO-

H-C-C=OO-HO-C-H

Homoisocitrate

CH2

C=OO-

CH2

CH2

C=OC=O

O-

α-ketoadipate

Aspartate Family:

Aspartate is formed by transamination of OAA using glutamate as the amino group

donor

Asparagine is formed by the amidation of the carboxyl R group of aspartate; in bacteria the

amino group comes from NH4

+; in other organisms it comes from glutatmate

Threonine, methionine and lysine biosynthesis in bacteria arises from the

common precursor aspartate via the intermediate β-aspartyl semialdehyde

HC-NH3+

COO-

CH2

COO-

HC-NH3+

COO-

CH2

O=C-O-P

ATPADP

Aspartate Aspartyl-β-phosphate

NADP+ + P

NADPH

HC-NH3+

COO-

CH2

O=C-H

β-Aspartyl semialdehyde

Pyruvate Family:

Alanine arises via transamination of pyruvate with glutamate as the amino

group donor

Valine, leucine and isoleucine are all essential amino acids; the intermediate

a-ketoisovalerate is the precursor to valine and leucine

3-PGA Family:

3-PGA is a substrate for oxidation to form 3-phosphohydroxypyruvate, which is an α-keto

acid transaminated by glutamate to yield 3-phosphoserine. Dephosphorylation produces

serine. Glycine is formed from CO2, NH

4+,

N5N10 Methylenetetrahydrofolate. Cysteine is formed by the transfer of a sulfhydryl group to

serine

H2C-O- P

HC-OH

O=C-O-

3-PGA

C=O

O=C-O-

H2C-O- P

3-Phosphohydroxypyruvate

HC-NH3+

O=C-O-

H2C-O- P

3-Phosphoserine

HC-NH3+

O=C-O-

H2C-OH

Serine

NAD+NADH

glutamate

α-kg

H2OP

PEP and Erythrose-4-P Family:

The aromatic amino acids are synthesized in a shared pathway that has chorismate as the key intermediate. Chorismate is common to the synthesis of compounds

with benzene rings including amino acids, Q, Qb, Vitamins E and K, and

lignin.

Chorismate is synthesized via the shikimate pathway; and the precursors to shikimate are

PEP and erythrose-4-P

Plants synthesize all 20 amino acids. Many herbicides act as inhibitors of enzymes in the

amino acid biosythetic pathways.

Glyphosate (roundup) is a PEP analogue that inhibits an enzyme in the shikimate

pathway and shuts down synthesis of aromatic amino acids

Sulfmeturon methyl (Oust) inhibits valine, leucine, isoleucine synthesis

Aminotriazole (Amitrole) inhibits histidine synthesis