Methionine 

Biosynthesis

Methionine is an essential amino acid in humans. It is not synthesized de novo in humans and other
animals, who must ingest methionine or methionine-containing proteins. In plants and
microorganisms, methionine biosynthesis belongs to the aspartate family. The main backbone is
derived from aspartic acid, while the sulfur may come from cysteine, methanethiol or hydrogen
sulfide.

First step in the biosynthesis of methionine, is phosphorylation of the aspartate by aspartate kinase.

Aspartate phosphate converted via β-aspartyl-semialdehyde into homoserine by two reduction steps

of the terminal carboxyl group. These two reactions are catalysed by aspartate-semialdehyde
dehydrogenase and homoserine dehydrogenase respectively.

Homoserine is then activated with an phosphate, succinyl or acetyl group on the hydroxyl. In plants
and possibly in some bacteria phosphate is used. In most organisms, an acetyl group is used to
activate the homoserine. In enterobacteria and a limited amount of other organisms, succinate is
used. The physiological basis for the preference of acetyl-CoA or succinyl-CoA is unknown.

The hydroxyl activating group is then replaced with cysteine, methanethiol or hydrogen sulfide. If it

reacts with cysteine, it produces cystathionine, which is catalysed by Cystathionine-γ-synthase.
cystathionine, cleaved by Cystathionine-β-lyase to yield homocysteine.

If it reacts with free hydrogen sulfide, it produces homocysteine. This is catalysed by O-
acetylhomoserine aminocarboxypropyltransferase.

If it reacts with methanethiol, it produces methionine directly. Methanethiol is a byproduct of

catabolic pathway of certain compounds, therefore this route is more uncommon.

If homocysteine is produced the thiol group is methylated, yielding methionine. This reaction is
catalysed by Methionine synthase.

The pathway utilising cysteine is called the "transsulfuration pathway", while the pathway utilising
hydrogen sulfide (or methanethiol) is called "direct-sulfurylation pathway".
Enzymes involved in the  methionine biosynthesis:

1 aspartokinase, 2 asparatateβ-semialdehyde dehydrogenase, 3 homoserine dehydrogenase, 4.

homoserine acyltransferase, 5. cystathionine-γ-synthase, 6.cystathionine-β-lyase, 14 methionine
synthase.
Histidine Biosynthesis

Histidine, also referred to as L-histidine, is an essential amino acid that is not synthesized de novo in
humans. Humans and other animals must ingest histidine or histidine-containing proteins.

Histidine is derived from 3 precursors: (a) PRPP contributes 5 carbon atoms (b) the purine ring of ATP
contributes a nitrogen and a carbon (c) glutamine contributes the second ring nitrogen.

Histidine is synthesized from phosphoribosyl pyrophosphate (PRPP), a biochemical intermediate, which

is made from ribose-5-phosphate by ribose-phosphate diphosphokinase during the pentose phosphate
pathway. The first reaction of histidine biosynthesis is the condensation of PRPP and adenosine
triphosphate (ATP) by the enzyme ATP-phosphoribosyl transferase.

pyrophosphohydrolase, then hydrolyzes the product of the condensation, phosphoribosyl-ATP,

producing phosphoribosyl-AMP (PRAMP), which is an irreversible step.

Then phosphoribosyl-AMP cyclohydrolase catalyzes the formation of

phosphoribosylformiminoAICAR-phosphate, which is then converted to phosphoribulosylformimino-
AICAR-P by the phosphoribosyl formimino-5- aminoimidazole-4-carboxamide-ribonucleotide
isomerase.

Glutamine amidotransferase, splits phosphoribulosylformimino-AICAR-P to AICAR and D-erythro-

imidazole-glycerol-phosphate.

After, imidazole glycerol-3-phosphate dehydratase forms imidazole acetol-phosphate by releasing water.

Imidazole acetol-phosphate then converts to L-histidinol-phosphate by L-histidinol phosphate

aminotransferase, which is then hydrolyzed to histidinolby histidinol phosphate phosphatase. 

histidinol dehydrogenase catalyzes the oxidation of L-histidinol to form L-histidinal, an amino aldehyde.

In the last step, L-histidinal is converted to L-histidine.
TryptophanBiosynthesis
Tryptophan is a non-polar aromatic amino acid. It is not synthesized from simpler substances in humans
and other animals, so it needs to be present in the diet in the form of tryptophan-containing proteins.
Plants and microorganisms commonly synthesize tryptophan from shikimic acid or anthranilate.
Tryptophan is synthesized from chorismate in a 5-step process. Chorismate acquires an amino group
from the side chain of glutamine and releases pyruvate to form anthranilate. Anthranilate then
undergoes condensation with phosphoribosyl pyrophosphate (PRPP), gives phosphoribosyl anthranilate
in presence of anthranilate PR transferase.
The ribose moiety of ribosylanthranilate undergoes rearrangement by PRA isomerase to yield enol-1-o-
carboxylphenylamino-1deoxyribulose-5-phosphate.
This intermediate is dehydrated and then decarboxylated to indole-3glycerol phosphate, this, in turn, is
transformed into indole.
After that tryptophan synthase catalyses the reaction between Indole with serine to form tryptophan.