Diseases related to aminoacid metabolismVipin mohan2011-09-112College of agricultureVellayani, tvm
Unlike glucose and fatty acids, amino acids are not stored by the bodyAmino acids in excess of biosynthetic needs are degraded.Degradation of amino acids involves: first stage removal of -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 -amino groups
With production of Free AmmoniaIn LiverSmall amount excreted in urine
A portion of the free ammonia is excreted in urine but most is used in the synthesis of urea3
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 -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)
Any amino acids in excess of the biosynthetic needs of the cell are rapidly degraded. The first phase of catabolism involves the removal of the -amino groups (usually by transamination and subsequent oxidative deamination), forming ammonia and the corresponding -keto acidthe carbon skeletons of amino acids. A portion of the free ammonia is excreted in the urine, but most is used in the synthesis of urea (Figure 19.1), which is quantitatively the most important route for disposing of nitrogen from the body.5
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 arthritisAlkaptonuria
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 ochronosisAortic 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.