DISEASES RELATED TO AMINOACID METABOLISM

VIPIN MOHAN2011-09-112COLLEGE OF AGRICULTURE

VELLAYANI, TVM

• Unlike glucose and fatty acids, amino acids are not stored by the body• Amino acids in excess of biosynthetic needs are degraded.• Degradation of amino acids involves: first stage removal of α-amino group ammonia (NH3)

Second stage remaining carbon skeleton energy metabolism

AMINO ACIDS CATABOLISM - OVERVIEW

1st phase of catabolism of amino acids:

Removal of the α-amino groupsWith

production of

Free Ammonia

In Liver

Small amount excreted in urine

Urea

• Blood level of ammoina must be kept very low, otherwise, hyperammonemia & CNS toxicity will occur

• To solve this problem, ammonia is transported from peripheral tissues to liver via formation of:

Glutamine (most tissues) Alanine (muscle)

2nd phase of A. A. catabolism Carbon skeletons of the α-ketoacids are

converted to common intermediates of energy producing, metabolic pathways

• ATP, CO2 & H2O (BY CITRIC ACID CYCLE) • GLUCOSE (BY GLUCONEOGENESIS)• FATTY ACIDS (FROM ACETYL COA)• KETONE BODIES (FROM ACETYL COA)

Amino acids accumulate in body fluids when there are genetic defects i.e. Inborn Errors of Metabolism. (IEM), that affect their metabolism or transport. Sometimes the opposite can happen and an IEM can result in the deficiency of an amino acid, for example some disorders of the urea cycle result in arginine deficiency.

- inherited disorder of the tyrosine metabolism caused by the absence of homogentisate oxidase. homogentisic acid is accumulated and excreted in the urine turns a black color upon exposure to air In children: urine in diaper may darken In adults: darkening of the ear dark spots on the on the sclera and cornea arthritis

Alkaptonuria

Urine turns a black color upon exposure to air

Accumulation of oxidized homogentisic acid pigment in connective tissue

(ochronosis)

Arthritis of the spine is a complication of alkaptonuria

ochronosis

Aortic valve stenosis in alkaptonuria

-is caused by an absence or deficiency of phenylalanine hydroxylase or of its tetrahydrobiopterin cofactor. Phenylalanine accumulates in all body fluids and converts to phenylpyruvate.

Defect in myelination of nervesThe brain weight is below normal.Mental and physical retardations.The life expectancy is drastically shortened.

Diagnostic criteria: phenylalanine level in the blood FeCl3 test DNA probes (prenatal)

Phenylketonuria

• Homocysteine is an intermediate in the metabolic pathway between methionine and cysteine.

• Homocysteine is present in body fluids in several forms.

• It is a sulphydryl compound that dimerises (oxidises) readily to form homocystine.

• The ‘free’ homocystine (dimer)in plasma and urine that was measured by amino acid analysis to detect and monitor homocystinuria.

• The most consistent and sensitive way to measure plasma homocysteine is to start by reducing all forms back to the monomer homocysteine initially.

Homocystinuria

• Homocystinuria causes chronic progressive disease characterised by Marfan-like skeletal abnormalities, mental retardation and severe thrombotic tendencies.

• Treatment is a combination of vitamin supplements, when effective, and a low methionine diet.

• Moderate hyperhomocysteinaemia is more common and is associated with increased risk of cardiovascular disease.

THANK YOU…