Course: Nutrition and Metabolism - National University acid catabolism.pdf · Fate of amino acids in the body 1. Amino acids are used for protein synthesis 2. Amino acids are used

Course: Nutrition and Metabolism

Part (3): Amino Acids & Protein Metabolism

Lecture (2): Amino Acids Catabolism

Dr. Nuha AminMobile: +249910050800

CatabolismUrea +

carbon

skeleton

Amino Acid Pool

Dietary amino

acids

Biosynthesis of

nitrogen compounds

fates of amino acids

Protein synthesis

Fate of amino acids in the body

1. Amino acids are used for protein synthesis

2. Amino acids are used for formation of nitrogen-

containing compounds

3. Amino acids in excess are degraded (used for energy)

Major dietary source of nitrogen is protein.

NITROGEN BALANCE

Nitrogen balance = nitrogen ingested - nitrogen excreted

(primarily as protein) (primarily as urea)

NITROGEN BALANCE

Nitrogen balance = nitrogen ingested - nitrogen excreted

(primarily as protein) (primarily as urea)

Nitrogen balance = 0

Positive nitrogen balance

Negative nitrogen balance.

Nitrogen in = nitrogen out300 g 300 g

Nitrogen in < nitrogen out250 g 300 g

Nitrogen in > nitrogen out

310 g 300 g

Normal nitrogen balance:

Normal, well fed adults

Positive N balance:

Growing or recovering animals

Negative N balance:

In starvation, trauma and cancer

AMINO ACID CATABOLISM

• Amino acids cannot be stored in the body.

• If there is an excess of amino acids, the

body will use them for energy production.

Amino acid degradation requires the

removal of the amino group as ammonia.

Amino Acid Catabolism

NH3Carbon Skeleton

Urea

Urea

Cycle

H2N C

O

NH2

Amino acid H3+N C

H

R

C

O

O-

Amino Acids Catabolism

excess amino acids are broken down into:

(1) urea excreted from body

(2) Carbon skeletons used as energy

Removal of NH3 group

Takes place in four steps

1.Transamination

2.Oxidative deamination

3.NH3 transport

4.Urea synthesis

TRANSAMINATION

• Is the transfer of amino group from a-amino acidto an a-keto acid

• A new amino acid and a new a-keto acid are formed

• Enzyme is called

transaminase

• Coenzyme is PLP

( vitamin B6)

Transamination reactions are

reversible reactions

Transamination Reactions

• Used in amino acid catabolism

• Used in amino acid biosynthesis

Product of transamination

• The removal of the amino groups of most amino

acids begins with the transfer of amino groups to

just one amino acid - glutamic acid .

• This is catalyzed by transaminase enzymes

which transfer the amino group from amino

acids to a compound called alpha-

ketoglutarate.

Alanine

Transaminase (ALT)

Aspartate

Transaminase (AST)

ALT And AST

alanine + a-ketoglutarate pyruvate + glutamate

aspartate + a-ketoglutarate oxaloacetate + glutamate

alanine

transaminase

aspartate

transaminase

Clinically Important Transaminases

(if high in blood, they indicate tissue damage)

1) Alanine transaminase (ALT) indicates liver damage

2) Aspartate transaminase (AST) indicates liver damage and myocardial infarction

2. Oxidative Deamination

• Oxidative deamination occurs on

glutamate because glutamate was the end

product of many transamination reactions.

• Oxidative deamination: Removes the

amino group from glutamate as ammonia

• This takes place in mitochondrial

matrix of cells.

•The enzyme is called glutamate dehydrogenase.

Glutamate dehydrogenase requires NAD+ or

NADP+ as cofactor.

Reversible reaction.

: Excess ammonia is toxic to animal

tissues. Other than amino acid

catabolism in tissues ammonia is also

produced as a result of nucleic acid

degradation.

Glutamine synthase catalyses the

synthesis of glutamine by adding the

ammonia to glutamate at the expense

of ATP hydrolysis.

Glutamine is a non-toxic carrier of

ammonia. It is transported to liver or

kidney via blood.

In liver or kidney mitochondria, the

glutamine is converted to glutamate

and ammonia. Ammonia is

incorporated in urea cycle in liver to

be excreted.

3.Transport of excess ammonia

Glucose-Alanine cycle:

Amino group from excess

glutamate produced in muscle as

a result of amino acid catabolism,

is transferred to pyruvate

resulting in the formation of

alanine.

Alanine is another safe way to

transport ammonia from muscle to

liver via blood.

In liver alanine aminotransferase

transfers the amino gp to glutarate

and pyruvate regenerated is used

in gluconeogenesis.

Glucose produced by

gluconeogenesis is transported to

muscle where it enters the

glycolysis.

Thus the excess puruvate and

ammonia generated in muscle are

safely transported to liver.

4.UREA CYCLE

– NH3 is produced from amino acid catabolism is

toxic and must be eliminated.

– NH3 is eliminated through the urea cycle

that occurs in the liver.

• Urea cycle is a five-step pathway carried out by

liver cells.

The urea cycle

Occurs in the liver.

Results in the formation of urea.

Urea is eliminated by excretion (urine).

L-arginino-

succinate

L-ornithine

fumarate

L-arginine

urea

H2O

argininosuccinate

lyase

arginase

NH4+ + CO2

carbamoyl

phosphate

L-citrulline

L- aspartate

ATP

AMP + PPi

Pi

2 ATP

2 ADP + Pi

ornithine

transcarbamoylase

argininosuccinate

synthase

carbamoyl-phosphate

synthase I

mitochondrial

matrix

Step 1First step combines CO2 and NH4

+ to form

carbamoyl phosphate

– Reaction requires ATP and H2O

– Takes place in the mitochondria

– Catalyzed by carbamoyl phosphate

synthetase

Step 2Carbamoyl phosphate condenses with the

amino acid ornithine to produce the amino acid

citrulline

– Occurs in the mitochondria

– Catalyzed by ornithine transcarbamoylase

Step 3Citrulline is transported to the cytoplasm

– Condenses with aspartate to produce

argininosuccinate

– Catalyzed by argininosuccinate

synthetase

– Requires energy released by ATP

hydrolysis

Step 4• Argininosuccinate cleaved to

produce the amino acid arginine and

fumarate of the citric acid cycle

• Reaction catalyzed by

argininosuccinate lyase

Step 5• Final reaction hydrolyzes arginine to

generate urea – the reaction product that is

excreted

• Reaction also regenerates ornithine, the

original reactant in the cycle

• Reaction is catalyzed by arginase

Metabolic disorders of urea

cycle

•All defects in urea synthesis

result in ammonia intoxication

•The defect is more serious in

the initial steps of urea

synthesis due to accumulation

of free ammonia

•Major clinical manifestations

are; vomiting, avoidance of high

protein diets, intermittent

ataxia, irritability, lethargy, and

mental retardation

•Disorder:

•1- hyperammonemia type I

•2- hyperammonemia typeII

•3- citrullinemia

•4- argininosuccinicaciduria

•5- hyperargininemia

•1- Hyperammonemia typeI:

•It is familial condition due to

defect in carbamoyl phosphate

synthetase deficiency

•All manifestation of

accumulation of ammonia…

•

•2- Hyperammonemia Type II:

•Due to deficiency of ornithine

transcarbamoylase

•It is an X linked defect.

Manifestations similar to type I.

There is elevated level of

glutamine in the blood,

cerebrospinal fluid and urine.

•3- Citrullinemia:

•Rare recessive inherited

disorder due to deficiency in

argininosuccinate synthase.

•1-2 grams of citrulline are

excreted in urine daily.

•Feeding arginine increase

excretion of citrulline and

feeding benzoate diverts

ammonia to hippurate.

•4- Argininosuccinicaciduria:

•Rare recessive inherited disorder due

to deficiency in argininosuccinase.

•There is elevated level of

argininosuccinate in the blood, CSF,

and urine.

•It can be of early or late onset.

•It is fatal early in life

•It is treated by arginine supplements

•5- hyperargininemia:

•Due to deficiency in arginase.

•It is characterized by elevated

arginine in the blood and CSF.

•Treated by low protein in the

diet

•Gene therapy…….