Faculty of MB ChB

Medical Biochemistry (BC 2410)

Amino Acids Metabolism

Disorders of Amino acids metabolism
 Amino Acid Metabolism (Outline)

• Amino acid synthesis

• Amino acid catabolism: carbon chain, amino
group and urea formation
• Disorders of amino acid metabolism and
regulation
Amino Acids metabolism disorders
• This final installment of the series of lecture
will look at the regulation of amino acids
metabolism and a few selected disorders of
amino acid metabolism
• The disorders highlighted here are autosomal
recessive and can be diagnosed primarily by
hematological studies
Regulation of amino acids metabolism
Metabolic pathways Regulatory agents Effect
Biosynthetic Anabolic Insulin Increased
Glucocorticoids Reduced
Well fed protein Increased
rich diet
Starvation Reduced
Transformations DNA transcription
(Transaminations) factors
Degradative Catabolic (Includes Insulin Reduced
oxidation and
integration into TCA
Glucocorticoids Increased
Well fed protein Reduced
rich diet
Starvation Increased
Urea formation N-acetylglutamate Increased
Well fed protein Increased
rich diet
 Amino acids metabolic disorders
• The selected amino acids metabolic disorders
include the following:-
1. Phenylketonuria PKU
2. Tyrosinemia
3. Homocystinuria
4. Non-ketotic hyperglycinemia
5. Maple syrup urine disease MSUD
 Phenylketonuria
• This condition is caused by a defect in the activity
of phenylalanine hydroxylase the enzyme that
converts the amino acid phenylalanine to tyrosine
• This results in accumulation of phenylalanine and
a decreased amount of tyrosine and other
metabolites.
• Tyrosine is a precursor of several important
hormones such as epinephrine and pigments of
skin hair and the eye.
 Phenylketonuria
• The presentation is as follows:-
1. Progressive developmental delay
2. Microcephaly
3. Behaviour disturbances
4. Seizures
5. Tendency to have hypopigmentation in hair,
appearing blonde and eyes, appearing blue eyed
due to decreased amounts of pigment melanin.
 Phenylketonuria
• The treatment is as follows:-
provide special formulas and with foods low in
phenylalanine and protein can reduce
phenylalanine levels to normal and maintain normal
intelligence.
However, there is a rare case of the condition that
results from impaired metabolism of biopterin, an
essential cofactor in the phenylalanine hydroxylase
reaction that may not respond to therapy.
 Tyrosinemia
• It is caused by a deficiency of
fumarylacetoacetate hydrolase the last
enzyme in tyrosine breakdown
• Features of classic tyrosinemia include:-
1. severe liver disease,
2. unsatisfactory weight gain
3. peripheral nerve disease
4. Kidney defects.
 Tyrosinemia
• Treatment consists of:-
• Administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-
1,3-cyclohexanedione (NTBC), a potent inhibitor of the
tyrosine catabolic pathway.
• NTBC treatment leads to improvement of liver, kidney,
and neurological symptoms,
• the occurrence of liver cancer however may not be
prevented.
• Liver transplantation may be required for severe liver
disease or if cancer develops.
 Homocystinuria
• Homocystinuria is caused by a defect in cystathionine beta-synthase
(or β-synthase), which leads to an accumulation of homocysteine.
• β-synthase is an enzyme that participates in the metabolism of
methionine during cysteine biosynthesis.
• The presentation includes;
1. A pronounced flush of the cheeks
2. a tall and thin frame
3. Lens dislocation
4. vascular disease
5. thinning of the bones (osteoporosis).
6. Mental retardation
7. psychiatric disorders
 Homocystinuria
• More than half of persons with
homocystinuria are responsive to treatment
with vitamin B6 (pyridoxine).
• Therapy with folic acid, betaine (a medication
that removes extra homocysteine from the
body), aspirin and dietary restriction of
protein and methionine also may be of benefit
 Non-ketotic hyperglycinemia
• Non-ketotic hyperglycinemia is caused by
elevated levels of the neurotransmitter glycine
in the central nervous system.
• These elevations are as a result of a defect in
the enzyme system responsible for cleaving
the amino acid glycine
 Non-ketotic hyperglycinemia
• Patients with the condition present with:-
• Seizures
• Low muscle tone
• Hiccups
• Breath holding
• Severe developmental impairment
 Non-ketotic hyperglycinemia
• There is currently no cure for this condition.
• Drugs that block the action of glycine (e.g.,
dextromethorphan)
• A low-protein diet
• glycine-scavenging medications (e.g., sodium
benzoate may alleviate symptoms.
 Maple syrup urine disease
• Maple syrup urine disease (MSUD) is a disorder of
branched-chain amino acid metabolism.
• The presentation because of the accumulation of
leucine, isoleucine, valine and their corresponding
oxoacids in body fluids
• The urine of some patients has a characteristic maple
syrup or burnt sugar smell
• The classic form of MSUD presents in infancy with
progressive neurological deterioration characterized
by seizures and coma.
 Maple syrup urine disease
• Treatment involves restricting proteins and feeding
with formulas deficient in the branched-chain amino
acids.
• Most patients have mental retardation despite
therapy
• However, early and careful treatment can result in
normal intellectual development.
• Milder forms of MSUD may be treated with simple
protein restriction and/or administration of thiamin
(vitB1).
 To Study
What is the role of raised plasma concentration
of Urea and nitrogenous wastes in blood in
disease?
Thank you