Amino Acid Pathway in Pharmacognosy

The amino acid pathway in pharmacognosy refers to biochemical reactions that lead to the biosynthesis of various amino acids. These amino acids are necessary for various biological processes such as energy production, cellular signaling, etc.

Amino acid pathway involves substrates that come from intermediates from other metabolic pathways and reactions. As you know, amino acids are of two types- essential and non-essential amino acids.

Essential amino acids	Non-essential amino acids
Arginine	Alanine
HIstidine	Asparagine
Isoleucine	Aspartate
Lysine	Cysteine
Methionine	Glutamate
Phenylalanine	Glutamine
Threonine	Glycine
Tryptophan	Proline
Valine	Serine
Leucine	Tyrosine

All of them are formed in one of the two types of amino acid pathways. Moreover, each of them are formed from different biomolecules or compounds or intermediates from other metabolic pathways.

Types of Amino Acid Pathway in Pharmacognosy

As mentioned, the amino acid pathway in pharmacognosy is of two types: the de novo pathway and the salvage pathway. The former refers to the formation of amino acids from scratch and the latter is the formation of amino acids from the degradation of other biomolecules such as proteins and nucleotides.

De novo Pathway

The de novo pathway involves the biosynthesis of amino acids from intermediary precursor molecules. The exact pathway is different for each amino acid. The intermediates for such amino acid pathways include α-ketoglutarate, oxaloacetate, phosphoenolpyruvate, erythrose 4-phosphate, 3-phosphoglycerate, and ribose 5-phosphate.

Each of these intermediates undergoes a different series of reactions with the help of enzymes. Such reactions include transamination, decarboxylation, and amination, to produce each amino acid. Some intermediates end up forming multiple amino acids, while ribose 5-phosphate produces only one amino acid – histidine.

Oxaloacetate from the TCA Cycle forms aspartate, which in turn forms four amino acids- asparagine, methionine, lysine, and threonine. Threonine will then form isoleucine.
Pyruvate from glycolysis produces alanine, leucine, and valine.
Ribose 5-phosphate produces histidine.
Phosphoenolpyruvate and erythrose 4-phosphate together form tyrosine, tryptophan, and phenylalanine. Phenylalanine will also form tyrosine
Alpha-ketoglutarate produces glutamate through a reductive amination reaction with the help of glutamate dehydrogenase. Glutamate will later form glutamine, arginine, and proline.
3-Phosphoglycerate produces serine. Serine will later form cysteine and glycine.

Biosynthetic Family	Amino acids
α-Ketoglutarate	Glutamate
	Glutamine
	Proline
	Arginine
Pyruvate	Alanine
	Valine
	Leucine
	Isoleusine
3-Phosphoglycerate	Serine
	Glycine
	Cysteine
Oxaloacetate	Aspartate
	Asparagine
	Methionine
	Threonine
	Lysine
Ribose 5-phosphate	Histidine
PEP+Erythrose 4-phosphate	Tryptophan
	Phenylalanine
	Tyrosine

Amino acids	Reactions
Glutamate	Transamination from 𝜶-Ketoglutarate
Glutamine	Glutamate → Acyl-phosphate intermediate → Glutamine
Proline	Glutamate → Acyl phosphate →Glutamate 𝛾-semialdehyde→Proline
Arginine	Glutamate →N-Acetylglutamate→N-acetyl-𝛾-glutamyl phosphate →N-acetylglutamate 𝛾-semialdehyde→N-Acetylornithine → L-citruline → Arginosuccinate → Arginine
Alanine	Transamination from pyruvate
Valine	Pyruvate → 2-Acetolactate → 2,3-Dihydroxyisovalerate →2-Ketoisovalerate → Valine
Leucine	Pyruvate → 2-Acetolactate → 2,3-Dihydroxyisovalerate →2-Ketoisovalerate → Leusine
Isoleusine	Pyruvate+2-Ketobutyrate → 2-Aceto-2-Hydroxybutyrate → 2,3-Dihydroxy-3-Methylvalerate → 2-Keto-3-Methylvalerate → Isoleusine
Serine	3-Phosphoglycerate → 3-Phosphohydroxypyruvate → 3-phosphoserine → Serine
Glycine	3-Phosphoglycerate → 3-Phosphohydroxypyruvate → 3-phosphoserine → Serine→ Glycine
Cysteine	Serine→ O-Acetylserine→Cysteine
Aspartate	Transamination of Oxaloacetate
Asparagine	Aspartate → Acyl-adenylate intermediate → Asparagine
Methionine	Homocysteine → N5-Methyl-tetrahydrofolate → Methionine
Threonine	Aspartate → Aspartyl phosphate → Aspartate semialdehyde → Homoserine → Homoserine phosphate → Threonine
Lysine	Aspartate → Aspartyl phosphate → Aspartate 4-semialdehyde → Dihydrodipiocolinate → Lysine
Histidine	Ribose 5-phosphate → Phosphoribosylpyrophosphate → Phosphoribosyl-ATP → Phosphoribosyl-AMP → Phosphoribosylformimino-AIC-RP → Phosphoribulosylformimino-AIC-RP → Imidazole glycerol-phosphate → Imidazole acetol-phosphate → Histidinol-phosphate → Histidinol → Histidine
Tryptophan	Chorismate → Anthranilate → N-(5’-Phosphoribosyl)-anthranilate → Indole-3-glycerol phosphate → Indole → Tryptophan
Phenylalanine	Chorismate → Prephenate → Phenylpyruvate → Phenylalanine
Tyrosine	Chorismate → Prephenate → p-Hydroxyphenylpyruvate→ Tyrosine

Salvage Pathway

The salvage pathway recovers amino acids from the degradation of proteins, protein turnover, or nucleotides. These salvaged amino acids are used for protein synthesis and in other metabolic reactions.

References

Metabolic pathways in higher plants and their determination. (n.d.). In UNIT-I. https://www.ramauniversity.ac.in/online-study-material/pharmacy/bpharma/vsemester/pharmacognosyandphytochemistry-ii/lecture-1.pdf
Lehninger (n.d.). AMINO ACID BIOSYNTHESIS. In Principles of Biochemistry (6th ed.). https://www.shivajicollege.ac.in/sPanel/uploads/econtent/031f78747fa81e295d4f96150c21493b.pdf
https://www.chem.uwec.edu/chem454_s09/chapter24.pdf
Desai, S. D. & Department of Biochemistry & Molecular Biology. (n.d.). Amino acids degradation and synthesis. https://www.medschool.lsuhsc.edu/biochemistry/Courses/Biochemistry201/Desai/Amino%20Acid%20Metabolism%20I%2010-14-08.pdf