BIOSYNTHESIS OF AMINO ACIDS

ValineIsoleucineLeucineThreonineLysineMethionineTryptophanePhenylalanineHistidine

These amino acids are not synthesizedin human cells. Therefore, they are nutritionally essential amino acids.

Their carbon sceleton can not be synthesized by human cells.

Histidine is synthesized in a limited amount by intestinal bacteria,therefore, it is semi-essential nutritionally.Arginine is synthesized in the urea cycle, but the rate is insufficient to meet the need during growth. However, it is also considered as semi-essential amino acid.

Amino acids are the precursors of several biologically active compounds!Glutamate and glycine are, for example, neurotransmitters!

BIOSYNTHETIC FAMILIES OF AMINO ACIDS IN PLANTS AND IN HUMAN CELLS

Oxaloacetate

Aspartate

Asparagine Methionine LysineThreonine

Isoleucine

Pyruvate

Alanine Valine Leucine

Ribose 5-phosphate

Histidine

Phosphoenolpyruvate+

Erythrose 4-phosphate

Phenylalanine

GlutamateSerine

Tryptophane

Tyrosine

-Ketoglutarate3-Phosphoglycerate

Glutamine Proline Arginine Cystein Glycine

THE BIOSYNTHESIS OF NUTRITIONALLY NON-ESSENTIAL AMINO ACIDS

Their carbon sceleton can be synthesized from the intermediates of

the citric acid cycle

or glycolysis

from other amino acids

Their NH2-group is obtained from glutamate (in most cases with the helpof specific transaminases)

L-glutamate dehydrogenase plays a central role in the biosynthesis ofamino acids, as well, since it can incorporate NH3 into -ketoglutarate.

-ketoglutarateoxaloacetate

pyruvatephosphoglycerate

1, The biosynthesis of glutamate from -ketoglutarate:

Two enzymes contribute to glutamate production:

a, glutamate dehydrogenase

b, transaminases

2, The biosynthesis of glutamine from glutamate:

Glutamine synthase is the other enzyme which can incorporate NH3

in order to save it for organic compounds

Glutamine is a NH2-group donor:

for the purine-ring, for the pirimidine ringfor the NH2-side groups of nucleotidesfor aminosugarsfor asparagine

glutamate glutamate - - semialdehyde

ornithine proline

arginine

slow rapid

3, The biosynthesis of arginine and proline from glutamate:

urea cycle

(semiessential)

4, The de novo synthesis of ornithine:

Synthesis of ornithine is an anaplerotic reaction of urea cycle in the absenceof dietary arginine

ornithine

arginine

urea

carbamoylphosphate

- NH2

In the absence of dietary arginine, arginine is used for protein synthesisand ornithine is the precursor of polyamines, the amount of ornithinewould be decreased in the urea cycle without anaplerotic reaction

The de novo synthesis of ornithine is slow (rate limiting), therefore,arginine is semi-essential.

dietary arginine

glutamate

urea cycle

5, The biosynthesis of aspartate from oxaloacetate:

COOH

CH2

O = C - COOH

COOH

CH2

NH2 - C - COOH

oxaloacetateaspartate

H

transaminase

glutamate

-ketoglutarate

aspartate is an NH2-group donorfor the synthesis of purine-ringfor the synthesis of adenylatein the urea cycle

aspartate is a precursor of the pyrimidine ring

6, Formation of asparagine from aspartate:

CONH2

CH2

NH2 - C - COOH

aspartate

H

glutamine

glutamate

COOH

CH2

NH2 - C - COOHH

asparagine

ATP + H2O AMP + PPi

Enzyme: asparagine synthetase

7, The biosynthesis of alanine from pyruvate:

CH3

C = O

COOH

pyruvatealanine

transaminase

glutamate

-ketoglutarate

CH3

C NH2

COOH

8, Formation of serine from phosphoglycerate:

COOH

HC - OH

CH2 – O – PO32+

COOH

C = O

CH2 – O – PO32+

COOH

H2N - CH

CH2 – O – PO32+

COOH

H2N - CH

CH2 – OH

NAD+

NADH + H+

tran

sam

inat

ion H2O

Pi

phospho-glycerate

phosphopyruvate

phospho-serine

serine

Serine is a precursor for: glycine, cystein and phospholipids

phospho-glyceratedehydrogenase

phosphatase

9, Formation of glycine from serine:

H2N – C - COOH

CH2 – OH

H

H2N – CH2 - COOH

tetrahydrofolic acid (FH4)

N5,N10-methylene-FH4

H2O

glycine

serine

5 10

NH

NH

N

N

N

N

5 5 5

10 10 10

tetrahydrofolate N5,N10-methylene-FH4N5-methyl-FH4

Ser Gly NADH + H+

NAD+H2C CH3

N5

10H N

O = C - H

N10-formyl-FH4

N

N

5

10H C

N5,N10-methenyl-FH4

NADP+

NADPH + H+

ATP

ADP + Pi

H

C=O

OH

formiate

H+ H2O

Conversion of one-carbon units attached to tetrahydrofolate

The metabolism of glycine

The major pathway of degradation: glycine cleavage complex

NH2 – CH2 – COOH

NH3

CO2

THF (FH4)

N5,N10-methylene-FH4

active C1

Glycine is an „inhibitory” neurotransmitter

Glycine is a precursor for

purine nucleotidesporphyrinscreatineglycine conjugates different drugs are conjugated by glycine in the

course of detoxication process

„nonketotic” hyperglycinemia: - the glycine cleavage complex is deficient- mental deficiency and many patients do not survive infancy

10, Formation of tyrosine from phenylalanine:

CH2

NH2 – CH – COOH

CH2

NH2 – CH – COOH

OH

phenylalanine

hydroxylase

DOPA

Dopamine

Norepinephrine

Epinephrine

Fumarate + acetoacetate

melanine(pigment)

phenylalanine

tyrosine

Phenylalanine hydroxylaseDeficiency: PHENYLKETONURIA

11, Formation of cysteine from serine:

The carbon skeleton of cysteine is derived from serine and the SH-group is derived from the sulphur of methionine(methinonine is nutritionally essential)

The degradation process of methionine yields homocysteine

CYSTATION SYNTHASE DEFICIENCY

Hyperhomocysteinemia and atherosclerosis

excess homocysteine can form hymocysteine thiolactone, a highlyreactive compound

CH2

CH2 S

H2N – CH – C = O

Homocysteine thiolactone reacts with free amino groups in low density lipoprotein (LDL) and causes them to aggregate and be endocytosed by macrophages. The lipid deposits form atheromas

About 25% of patients with atherosclerosis who exhibit none of the other risk factors have been found to be deficient in cystatione synthase!!

DEVLIN

vitamine B12

12, Formation of taurine from cysteine:

cysteine dioxygenase.

sulfinoalanine decarboxylase

Taurine is conjugated via its amino terminal group (bile acids)Neurotransmission, long-term potentiation (LTP) in the striatum/hippocampusMembrane stabilization, Taurine and catsTaurine is an essential dietary requirement for feline health, since cats cannot synthesize the compound. The absence of taurine causes a cat's retina to slowly degenerate, causing eye problems and (eventually) irreversible blindness — a condition known as central retinal degeneration (CRD),[