Download MBBS Biochemistry PPT 38 Biosynthesis Of Non Essential Amino Acids Lecture Notes

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Department of Biochemistry

Specific Learning Objectives

1. Biosynthesis of non-essential amino acids (body can synthesize them

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from other proteins so not essential to eat them)
Essential and non-essential amino acids

? Essential

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aa:

Cannot

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be

synthesize in body so "essential"

to eat them from dietary food.

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? Non-essential:

Body

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can

synthesize them from other

proteins so not essential to eat

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them

Table 27.1. Harper's Illustrated Biochemistry 30th Edition

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Overview of amino acid biosynthesis

Fig22.11: Lehninger Principles of Biochemistry by David L Nelson, 6th Ed.
Glutamate

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? Glutamate, is formed by the amidation of -

ketoglutarate, catalyzed by mitochondrial

glutamate dehydrogenase

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? It require NADPH as a reducing agent

? The reaction strongly favors glutamate

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synthesis, which lowers the concentration of

cytotoxic ammonium ion.

Glutamine

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? Amidation of glutamate to glutamine catalyzed by

glutamine synthetase, involves intermediate formation of

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-glutamyl phosphate

? In Binding of glutamate and ATP, glutamate attacks -

phosphorus of ATP, forming -glutamyl phosphate and

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ADP

? NH4+ binds, and uncharged NH attacks -glutamyl

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3

phosphate

? Release of Pi and of a proton from -amino group of

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tetrahedral intermediate then al ows release of product,

glutamine
Alanine & Aspartate

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? Transamination of pyruvate forms

alanine

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? Similarly,

transamination

of

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oxaloacetate forms aspartate

Asparagine

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? Conversion of aspartate to asparagine,

catalyzed by asparagine synthetase

? Reaction involves intermediate formation of

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aspartyl phosphate

? Coupled hydrolysis of PPi to Pi by

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pyrophosphatase, ensures that reaction is

strongly favored
Serine

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? Oxidation of -hydroxyl group of glycolytic

intermediate 3-phosphoglycerate, catalysed

by 3-phosphoglycerate dehydrogenase,

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converts it to 3-phosphohydroxypyruvate

? Transamination

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and

subsequent

dephosphorylation then form serine

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Glycine

? Glycine aminotransferases can catalyze

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synthesis of glycine from glyoxylate and

glutamate or alanine.

? Unlike most aminotransferase reactions, these

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strongly favor glycine synthesis

? Important mammalian routes for glycine

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formation are from choline
Cont--

? Glycine formation are from

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serine

Proline

? Initial reaction of proline biosynthesis converts

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-carboxyl group of glutamate to mixed acid

anhydride of glutamate -phosphate

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? Subsequent reduction forms glutamate -

semialdehyde, which following spontaneous

cyclization is reduced to proline

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Cysteine

? While not nutritionally essential, cysteine is

formed from methionine, which is nutritionally

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essential

? Following conversion of methionine to

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homocysteine, homocysteine and serine form

cystathionine, whose hydrolysis forms cysteine

and homoserine

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Tyrosine

? Phenylalanine hydroxylase converts phenylalanine to

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tyrosine

? Phenylalanine hydroxylase reaction is irreversible,

dietary tyrosine cannot replace phenylalanine

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? Catalysis by this mixed-function oxidase incorporates

one atom of O2 into para position of phenylalanine

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and reduces other atom to water

? Reducing power, provided as tetrahydrobiopterin

derives ultimately from NADPH

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Valine, Leucine, & Isoleucine

While leucine, valine, and isoleucine are all nutritionally essential

amino acids, tissue aminotransferases reversibly interconvert all

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three amino acids and their corresponding -keto acids

These -keto acids thus can replace their amino acids in diet

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Hydroxyproline & Hydroxylysine

? Peptidyl hydroxyproline and hydroxylysine

arise from proline and lysine

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? Hydroxylation of peptidyl prolyl and peptidyl

lysyl residues, catalyzed by prolyl hydroxylase

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and lysyl hydroxylase of skin, skeletal muscle,

and granulating wounds requires, in addition to

the substrate, molecular O2, ascorbate, Fe2+,

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and -ketoglutarate

? For every mole of proline or lysine

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hydroxylated, one mole of -ketoglutarate is

decarboxylated to succinate

? A deficiency of the vitamin C required for these

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two hydroxylases results in scurvy
Two Clinical-cases discussed

Group Discussion and Rivision

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Subtopics of previous and today's class discussed in groups.
Reference Books

19

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1) Lehninger Principles of Biochemistry, 6th Ed.
2) Harper's Il ustrated Biochemistry-30th edition
3) Biochemistry, Lippincott's Il ustrated Reviews, 6th Ed
4) Gregory S. Ducker and Joshua D Rabinowitz. Cell Metab. 2017 Jan

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10;25(1):27-42

Thank you