This document discusses diseases related to amino acid metabolism, including alkaptonuria, phenylketonuria, and homocystinuria. It provides an overview of amino acid catabolism and degradation pathways. Specific genetic defects that cause these diseases are described, including symptoms and diagnostic criteria. Treatment options are mentioned for managing associated health issues.

1. DISEASES RELATED TO
AMINOACID METABOLISM
VIPIN MOHAN
2011-09-112
COLLEGE OF
AGRICULTURE

2. • 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

3. 1st phase of catabolism of amino acids:
Removal of the α-amino groups
With
production
of
Free
Ammonia
In Liver
Small amount excreted in
urine
Urea

4. • 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)

5. 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)

6. 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.

7. - 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

9. 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

10. -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 nerves
The 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

11. • 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

12. • 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.