Amino Acid Metabolism-3

Biosynthesis of Nonessential Amino Acid Inborn Errors of Amino Acid Metabolism Faisal Khatib MD;PhD Faculty of Medicine, University of Jordan

Biosynthesis of Nonessential Amino Acids

From -keto acids
Alanine, Aspartate, Glutamate Serine

From essential amino acids

Cysteine, Tyrosine

From other amino acids

Amidation of Glutamine, Asparagine Proline Interconversion of Serine and Glycine

Production of

Serine
From

3phosphoglycer ate

Tyrosine can be Produced by Hydroxylation of Phenylalanine

Cysteine can be Produced from Methionine

Methionine

Homocysteine Serine Cystathionine ketobutyrate Cysteine

Asparagine is Produced by Amidation of Aspartate

Glutamine is the Donor of Amide Group

Defects of Amino Acid Metabolism

Inborn errors of amino acid metabolism Mutant gene >>> Abnormal Enzyme Mostly recessive Most of them are rare 1:250,000 Few are common Total or Partial Loss of Activity

Defects of Amino Acid Metabolism

Loss of enzyme activity

Accumulation of metabolites

Mental retardation (in many diseases)

Phenylketonuria (PKU)
Relatively common Can be easily detected More than one form exist Can respond to dietary treatment

BH2 Reductase

BH2 Synthetase

Tetrahydrobiopterin is required in the synthesis of some neurotransmitters

PKU is characterized by high plasma level of phenylalanine and its metabolites

Diagnosis of PKU
Early diagnosis is important Neonatal diagnosis 48 hours after birth Testing at birth >>>False negative Antenatal diagnosis
Genetic methods Forty mutations or more are known

Treatment of PKU
Most natural proteins contain Phenylalanine Synthetic amino acid preperations with some natural food of low Phe content. Repeated measurement of plasma phe level Tyrosine must be supplied

Treatment of PKU
Must begin early after birth to prevent mental retardation

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Treatment of PKU
Life long management is necessary

Maternal PKU
Fetus can be affected if untreated mother
CNS manifestations Congenital heart defects

Dietary control should start prior to conception and throughout pregnancy

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Maple Syrup Urine Disease

Deficiency of branchedchain -keto acid dehydogenase Val, Leu, Ile Accumulation of Amino Acids and -keto acid Fatal disease dehydrogenase Acyl CoA Val, Leu, Ile transaminase -keto acid analogs

Maple Syrup Urine Disease

Classification
Classic type
Little or no Enzyme activity Symptoms within first several days

Intermediate form
Enzyme 3-15% of normal Onset from infancy to childhood

Thiamine responsive form Large doses of thiamine

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Maple Syrup Urine Disease Diagnosis and Management

Measurement of enzyme in leukocytes Early diagnosis is essential Treatment should start from day 1 Synthetic formula low in branched amino acids

Albinism
Defect in tyrosine metabolism Tyrosine Melanin Partial or full absence of the enzyme Different forms, different modes of inheritance

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Complete albinism

Homocystineuria
High plasma and urinary level of homocysteine methionine Low level of cysteine Premature arteriosclerosis

Some patients are responsive to B6 Restriction of methionine Supplementation with vit. B6, B12 folate

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Alkaptonuria
Rare but has historical importance Homogentisic acid oxidase Accumulation of homogenitisic and excretion in urine Black pigment Not life threatening

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