Download MBBS Biochemistry PPT 23 Biosynthesis Lecture Notes

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Department of Biochemistry

Learning Objectives

1. Biosynthesis of non-essential amino acids:

? Alanine

? Asparagine & Aspartate

? Cysteine

? Glutamate

? Glutamine

? Glycine

? Proline

? Serine
? Tyrosine

? Hydroxyproline and Hydroxylysine
Biosynthesis of non-essential amino

acids

Table 27.1. Harper's Illustrated Biochemistry 30th Edition
Glutamate

? Glutamate, is formed by amidation of

-ketoglutarate,

catalyzed

by

mitochondrial

glutamate

dehydrogenase

? It require NADPH as a reducing agent

? This

reaction

strongly

favors

Fig 27.1. Harper's Illustrated Biochemistry 30th Edition

glutamate synthesis, which lowers

the

concentration

of

cytotoxic

ammonium ion.

Cont--

? NH4+ binds, and uncharged NH3 attacks -glutamyl phosphate

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

tetrahedral intermediate then allows release of the product,

glutamine
Glutamine

? Amidation of glutamate to

glutamine catalyzed by glutamine

synthetase

? Glutamine, is amino group donor

in formation of many biosynthetic

products, as well as being a

Fig 27.2. Harper's Illustrated Biochemistry 30th Edition

storage form of ammonia

Cont--

? Mammalian Glutamine synthetases are activated by -

ketoglutarate, the product of glutamate's oxidative

deamination

? This prevents the accumulation of the ammonia produced by

that reaction
Alanine

? Transamination of pyruvate forms

alanine by aminotransferase

Fig.26.54. Biochemistry. 4th edition by Donald Voet and Judith G. Voet

Aspartate

? Transamination of oxaloacetate

forms

aspartate

by

aminotransferase

Fig.26.54. Biochemistry. 4th edition by Donald Voet and Judith G. Voet
Asparagine

? Conversion of aspartate to

asparagine,

by

amidation

reaction and catalyzed by

asparagine synthetase

? ATP is needed to activate the

receptor a carboxyl group

Fig 27.5. Harper's Illustrated Biochemistry 30th Edition

? Asparagine

is

readily

synthesized in most cells, but

some leukemic cells lost this

ability

Cont--

? Therapeutic approach for patients with asparagine synthetase

deficient tumors is treatment with exogenous asparaginase to

hydrolyze the bloodborne asparagine on which these cells rely

? Normal cells synthesize and degrade asparagine.
Serine

The pathway enzymes are:
? 3-phosphoglycerate dehydrogenase

? PLP-dependent aminotransferase

? Phosphoserine phosphatase.

Fig.26.58. Biochemistry. 4th edition by Donald Voet and Judith G. Voet

Glycine

? Glycine aminotransferases can catalyze

synthesis of glycine from glyoxylate and

glutamate or alanine.

? Unlike most aminotransferase reactions, these

strongly favor glycine synthesis

? Important mammalian routes for glycine

formation are from choline

Fig 27.8. Harper's Illustrated Biochemistry 30th Edition
Cont--
Serine participates in glycine

synthesis in two ways:

1. Direct conversion of serine to

glycine by serine hydroxymethyl

transferase in a reaction that also

yields N5,N10-methylene-THF

Fig 27.9. Harper's Illustrated Biochemistry 30th Edition

2. Condensation of the N5,N10-

methylene-THF with CO2 and by the

glycine cleavage system

Proline

? Initial reaction of proline biosynthesis

converts -carboxyl group of glutamate

to mixed acid anhydride of glutamate -

phosphate

? Subsequent reduction forms glutamate

-semialdehyde,

which

following

spontaneous cyclization is reduced to

proline

Fig 27.10. Harper's Illustrated Biochemistry 30th Edition
Cysteine
? While not nutritionally essential, cysteine

is formed from methionine

Cystathione -synthetase

? Require for formation of glutathione,

which is imp for transport of aa

? Homocystinuria occur due to deficiency

of cystathionine -synthase

Fig 27.11. Harper's Illustrated Biochemistry 30th Edition

Tyrosine

? Phenylalanine hydroxylase converts

phenylalanine to tyrosine

? Its irreversible reaction, dietary

tyrosine cannot replace phenylalanine

Fig 27.12. Harper's Illustrated Biochemistry 30th Edition
Cont--

? Catalysis by this mixed-function oxidase incorporates one atom

of O into para position of phenylalanine and reduces other

2

atom to water

? Reducing power, provided as tetrahydrobiopterin derives from

NADPH

Branched chain aa (Valine, Leucine, & Isoleucine)

? While leucine, valine, and isoleucine are all nutritionally

essential aa , tissue aminotransferases reversibly interconvert

all three aa and their corresponding -keto acids.

? These -keto acids can replace their aa in diet.
Hydroxyproline & Hydroxylysine

? Peptidyl

hydroxyproline

and

hydroxylysine arise from proline and

lysine

? Hydroxylation of peptidyl prolyl and

peptidyl lysyl residues, catalyzed by

prolyl

hydroxylase

and

lysyl

hydroxylase of skin, skeletal muscle,

and granulating wounds requires, in

Fig 27.13. Harper's Illustrated Biochemistry 30th Edition

addition to the substrate, molecular

O2, ascorbate, Fe2+, and -

ketoglutarate

Cont--

? For every mole of proline or lysine hydroxylated, one mole of -

ketoglutarate is decarboxylated to succinate

? A deficiency of the vitamin C required for these two

hydroxylases results in scurvy
Amino acid degradation and related

disorders

Summary of Amino acid Catabolism

Fig18.15: Lehninger Principles of Biochemistry by David L Nelson
Genetic disorders related to Amino-acid catabolism

Table 18.2: Lehninger Principles of Biochemistry by David L Nelson

Interaction with students

? Distributed subtopics of class to students for participate in group

discussion in next class.
Reference Books

1) Lehninger Principles of Biochemistry
2) Harper's Illustrated Biochemistry-30th Ed
3) Biochemistry, Lippincott's Illustrated Reviews, 6th Ed
4) Text Book of Medical Biochemistry by Chatterjee & Rana Shinde,

8th Ed

5) Biochemistry, Donald Voet and Judith G. Voet, 4th Ed.

27

Thank you

This post was last modified on 05 April 2022