Course: Nutrition and Metabolism

Part (3): Amino Acids & Protein Metabolism

Lecture (4): Biosynthesis of Non-essential Amino Acids

Dr. Nuha AminMobile: +249910050800

Classification of Amino Acids

According to the diet, amino acids can be classified into

• Essential amino acids -our body cannot

synthesize them.

• Nonessential amino acids-our body can

synthesize them

Essential Amino Acids in Humans10 amino acids are essential and must be provided by

the diet

– Phenylalanine

– Valine

– Threonine

– Tryptophan PVT TIM HALL

– Isoleucine

– Methionine

– Histidine *

– Arginine *

– Leucine

– Lysine

*Required to some degree in young growing children.

Non-essential amino acids in humans

Amino acids that can be synthesized in the body.

Alanine

Asparagine

Aspartate

Glutamate

Glutamine

Glycine

Proline

Serine

Cysteine (from Met*)

Tyrosine (from Phe*)

* Essential amino acids

SYNTHESIS OF NON-ESSENTIAL AMINO

ACIDS

• All ,except tyrosine, are synthesized from

common intermediates of the TCA cycle

and glycolysis.

– PYRUVATE

– OXALOACETATE

– -KETOGLUTARATE

– 3-PHOSPHOGLYCERATE

Synthesis of Amino Acids

• In humans, transamination of compounds from glycolysis or the citric acid cycle produces nonessential amino acids.

Biosynthesis of amino acids: transamination reactions

amino acid1 +-keto acid2 amino acid2 +a-keto acid1

From pyruvate

• alanine

CH3 C C-OH

O O

Glutamate -ketoglutarate

CH3 CH C-OH

NH2 O

Pyruvate Alanine

Alanine

transaminase

PLP

1. Alanine Biosynthesis

From oxaloacetate

• Aspartate

• Asparagine

O

Glutamate -ketoglutarate

NH2

Oxaloacetate Aspartate

Aspartate

transaminase

PLPHO-C-CH2-CH-C-OH

O O

HO-C-CH2-C-C-OH

O O

2. Aspartate Biosynthesis

Chapter 17

3.Asparagine Biosynthesis

Chapter 17

4.Glutamate synthesis

• Addition of an amino group to -ketoglutarate

produces glutamate.

• The enzyme is called glutamate dehydrogenase

5.Glutamine synthesis

• Glutamine is synthesized by adding another amino

group to glutamate using glutamine synthetase.

Chapter 17

6. Proline and Arginine Biosynthesis

7.Serine Biosynthesis

8. Glycine Biosynthesis

NH2 C C-OH

CH2 O

THFmethylene THF

NH2 CH C-OH

H O

Serine Glycine

Serine hydroxymethyltransferase

OH

The sulfur for cysteine synthesis comes from the essential

amino acid methionine.

SAM serves as a precurosor for numerous methyl transfer reactions (e.g. the

conversion of norepinephrine to epinenephrine).

9.Cysteine Biosynthesis

Condensation of ATP and

methionine yield S-

adenosylmethionine (SAM)

SAM

1. Conversion of

SAM to

homocysteine.

2. Condensation of

homocysteine

with serine to

cystathione.

3. Cystathione is

cleavaged to

cysteine.

*

Methionine is catabolised through cysteine synthesis

Propionyl

CoA

Succinyl CoA

10. Tyrosine Biosynthesis

INBORN ERRORS OF METABOLISM

Genetic diseases!

What is an inborn error disease?

A

D

B Csubstrate

excess

Toxic compound

no product

26

– Absence of phenylalanine hydroxylase

enzyme

1.Phenylketonuria

Phenylketonuria (PKU) Disease

CH2CCO2-

O

Phe

Tyr

Transamination

Phenylpyruvate

(urine)

The clinical symptoms of PKU are

caused by

• the accumulation of phenylalanine in the blood

that is 30-50 times higher than normal.

• This high level of phenylalanine leads to the

production of phenylalanine metabolites such as

phenylpyruvate, phenylacetate and

phenyllactate

• these lead to the neurological and developmental

problems.

Disease symptoms of PKU include

• severe mental retardation,

• stunted growth

Treatment of Phenylketonuria (PKU)

Decreasing dietary PHE prevents brain damage

in children with PKU.

PHE is less damaging once brain has developed.

Phenylketonuria

Alkaptonuria

Tyrosinemia II

Tyrosinemia I

Diseases of Phenylalanine/

Tyrosine Metabolism

33

– Absence of homogentisate oxidase activity

2.Alkaptonuria

Dark

urine

Alkaptonuria - Clinical signs

• The pigmentation is called ochronosis.

– Note the pigmentation of the ear and eyes.

• The arthritis is associated with calcification of joints.

3.Maple syrup urine disease

Genetic disease caused by deficiency of Branched Chain alpha-Keto Acid Dehydrogenase

Alpha keto amino acids, valine, isolucine and

leucine will accumulated in the blood and excreted

in the urine (smells like maple syrup).

If untreated, mental retardation and early death.

COO-

CH3+N

CHH3C

CH3

H

COO-

CH3+N

CHH3C

CH2

H

CH3

COO-

CH3+N

CH2

CH

H

CH3

H3C

COO-

C

CHH3C

CH3

O

COO-

C

CHH3C

CH2

O

CH3

COO-

C

CH2

CH

O

CH3

H3C

C

CHH3C

CH3

O SCoA

C

CHH3C

CH2

CH3

O SCoA

C

CH2

CH

CH3

H3C

O SCoA

CoASH CO2

-keto acid

dehydrogenase

complexbranched-

chain

amino

transferase

valine

isoleucine

leucine

Acyl-CoA

derivatives

Breakdown of branched amino acids

Maple syrup urine disease

The -keto acids of VAL, ILE and LEU are not broken down.

Deficiency of -keto acid dehydrogenase.

Urine smells like maple syrup.

High concentrations cause mental retardation.

Damage can be minimized by restricting these

amino acids in the early diet.

H2C CH C

CH3

COOH

O

H3CH3C CH C

CH3

COOH

O

H C CH2 C COOH

O

H3C

CH3