Download MBBS Biochemistry PPT 23 Biosynthesis Lecture Notes

--- Content provided by‍ FirstRanker.com ---

1. Biosynthesis of non-essential amino acids:

? Alanine

? Asparagine & Aspartate

--- Content provided by​ FirstRanker.com ---

? Cysteine

? Glutamate

--- Content provided by‌ FirstRanker.com ---

? Glutamine

? Glycine

? Proline

--- Content provided by‌ FirstRanker.com ---

? Serine
? Tyrosine

? Hydroxyproline and Hydroxylysine

--- Content provided by⁠ FirstRanker.com ---

Biosynthesis of non-essential amino

acids

Table 27.1. Harper's Illustrated Biochemistry 30th Edition

--- Content provided by​ FirstRanker.com ---

Glutamate

? Glutamate, is formed by amidation of

-ketoglutarate,

--- Content provided by‍ FirstRanker.com ---

catalyzed

by

--- Content provided by⁠ FirstRanker.com ---

mitochondrial

glutamate

dehydrogenase

--- Content provided by‌ FirstRanker.com ---

? It require NADPH as a reducing agent

? This

--- Content provided by​ FirstRanker.com ---

reaction

strongly

favors

--- Content provided by FirstRanker.com ---

Fig 27.1. Harper's Illustrated Biochemistry 30th Edition

glutamate synthesis, which lowers

--- Content provided by‍ FirstRanker.com ---

the

concentration

of

--- Content provided by‍ FirstRanker.com ---

cytotoxic

ammonium ion.

--- Content provided by‍ FirstRanker.com ---

Cont--

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

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

--- Content provided by⁠ FirstRanker.com ---

tetrahedral intermediate then allows release of the product,

glutamine
Glutamine

--- Content provided by FirstRanker.com ---

? Amidation of glutamate to

glutamine catalyzed by glutamine

--- Content provided by FirstRanker.com ---

synthetase

? Glutamine, is amino group donor

in formation of many biosynthetic

--- Content provided by‍ FirstRanker.com ---

products, as well as being a

Fig 27.2. Harper's Illustrated Biochemistry 30th Edition

--- Content provided by‌ FirstRanker.com ---

storage form of ammonia

Cont--

? Mammalian Glutamine synthetases are activated by -

--- Content provided by⁠ FirstRanker.com ---

ketoglutarate, the product of glutamate's oxidative

deamination

--- Content provided by‌ FirstRanker.com ---

? This prevents the accumulation of the ammonia produced by

that reaction
Alanine

--- Content provided by‍ FirstRanker.com ---

? Transamination of pyruvate forms

alanine by aminotransferase

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

--- Content provided by‍ FirstRanker.com ---

Aspartate

? Transamination of oxaloacetate

--- Content provided by⁠ FirstRanker.com ---

forms

aspartate

by

--- Content provided by‌ FirstRanker.com ---

aminotransferase

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

--- Content provided by FirstRanker.com ---

? Conversion of aspartate to

asparagine,

--- Content provided by FirstRanker.com ---

by

amidation

reaction and catalyzed by

--- Content provided by FirstRanker.com ---

asparagine synthetase

? ATP is needed to activate the

--- Content provided by​ FirstRanker.com ---

receptor a carboxyl group

Fig 27.5. Harper's Illustrated Biochemistry 30th Edition

? Asparagine

--- Content provided by‌ FirstRanker.com ---

is

readily

--- Content provided by​ FirstRanker.com ---

synthesized in most cells, but

some leukemic cells lost this

ability

--- Content provided by​ FirstRanker.com ---

Cont--

? Therapeutic approach for patients with asparagine synthetase

--- Content provided by FirstRanker.com ---

deficient tumors is treatment with exogenous asparaginase to

hydrolyze the bloodborne asparagine on which these cells rely

? Normal cells synthesize and degrade asparagine.

--- Content provided by‌ FirstRanker.com ---

Serine

The pathway enzymes are:
? 3-phosphoglycerate dehydrogenase

--- Content provided by⁠ FirstRanker.com ---

? PLP-dependent aminotransferase

? Phosphoserine phosphatase.

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

--- Content provided by‌ FirstRanker.com ---

Glycine

? Glycine aminotransferases can catalyze

--- Content provided by FirstRanker.com ---

synthesis of glycine from glyoxylate and

glutamate or alanine.

? Unlike most aminotransferase reactions, these

--- Content provided by‌ FirstRanker.com ---

strongly favor glycine synthesis

? Important mammalian routes for glycine

--- Content provided by‌ FirstRanker.com ---

formation are from choline

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

--- Content provided by⁠ FirstRanker.com ---

synthesis in two ways:

1. Direct conversion of serine to

--- Content provided by‍ FirstRanker.com ---

glycine by serine hydroxymethyl

transferase in a reaction that also

yields N5,N10-methylene-THF

--- Content provided by‍ FirstRanker.com ---

Fig 27.9. Harper's Illustrated Biochemistry 30th Edition

2. Condensation of the N5,N10-

--- Content provided by​ FirstRanker.com ---

methylene-THF with CO2 and by the

glycine cleavage system

Proline

--- Content provided by​ FirstRanker.com ---

? Initial reaction of proline biosynthesis

converts -carboxyl group of glutamate

--- Content provided by⁠ FirstRanker.com ---

to mixed acid anhydride of glutamate -

phosphate

? Subsequent reduction forms glutamate

--- Content provided by‌ FirstRanker.com ---

-semialdehyde,

which

--- Content provided by⁠ FirstRanker.com ---

following

spontaneous cyclization is reduced to

proline

--- Content provided by FirstRanker.com ---

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

--- Content provided by‍ FirstRanker.com ---

is formed from methionine

Cystathione -synthetase

? Require for formation of glutathione,

--- Content provided by⁠ FirstRanker.com ---

which is imp for transport of aa

? Homocystinuria occur due to deficiency

--- Content provided by​ FirstRanker.com ---

of cystathionine -synthase

Fig 27.11. Harper's Illustrated Biochemistry 30th Edition

Tyrosine

--- Content provided by​ FirstRanker.com ---

? Phenylalanine hydroxylase converts

phenylalanine to tyrosine

--- Content provided by​ FirstRanker.com ---

? Its irreversible reaction, dietary

tyrosine cannot replace phenylalanine

Fig 27.12. Harper's Illustrated Biochemistry 30th Edition

--- Content provided by‌ FirstRanker.com ---

Cont--

? Catalysis by this mixed-function oxidase incorporates one atom

of O into para position of phenylalanine and reduces other

--- Content provided by‌ FirstRanker.com ---

2

atom to water

--- Content provided by‍ FirstRanker.com ---

? Reducing power, provided as tetrahydrobiopterin derives from

NADPH

Branched chain aa (Valine, Leucine, & Isoleucine)

--- Content provided by⁠ FirstRanker.com ---

? While leucine, valine, and isoleucine are all nutritionally

essential aa , tissue aminotransferases reversibly interconvert

--- Content provided by⁠ FirstRanker.com ---

all three aa and their corresponding -keto acids.

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

--- Content provided by‍ FirstRanker.com ---

? Peptidyl

hydroxyproline

and

--- Content provided by​ FirstRanker.com ---

hydroxylysine arise from proline and

lysine

--- Content provided by⁠ FirstRanker.com ---

? Hydroxylation of peptidyl prolyl and

peptidyl lysyl residues, catalyzed by

prolyl

--- Content provided by‌ FirstRanker.com ---

hydroxylase

and

--- Content provided by​ FirstRanker.com ---

lysyl

hydroxylase of skin, skeletal muscle,

and granulating wounds requires, in

--- Content provided by​ FirstRanker.com ---

Fig 27.13. Harper's Illustrated Biochemistry 30th Edition

addition to the substrate, molecular

--- Content provided by‌ FirstRanker.com ---

O2, ascorbate, Fe2+, and -

ketoglutarate

Cont--

--- Content provided by‍ FirstRanker.com ---

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

ketoglutarate is decarboxylated to succinate

--- Content provided by⁠ FirstRanker.com ---

? A deficiency of the vitamin C required for these two

hydroxylases results in scurvy
Amino acid degradation and related

--- Content provided by⁠ FirstRanker.com ---

disorders

Summary of Amino acid Catabolism

Fig18.15: Lehninger Principles of Biochemistry by David L Nelson

--- Content provided by​ FirstRanker.com ---

Genetic disorders related to Amino-acid catabolism

Table 18.2: Lehninger Principles of Biochemistry by David L Nelson

Interaction with students

--- Content provided by⁠ FirstRanker.com ---

? Distributed subtopics of class to students for participate in group

discussion in next class.
Reference Books

--- Content provided by​ FirstRanker.com ---

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,

--- Content provided by FirstRanker.com ---

8th Ed

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

--- Content provided by‌ FirstRanker.com ---

27

Thank you