INBORN ERRORS/ HEREDITARY ENZYME DEFECTS IN AMINO ACID METABOLISM
➢ 1. Phenylketonuria (PKU)/ Hyperphenylalaninemia
➢ It results due to homozygous defect of phenylalanine hydroxylase
resulting into accumulation of phenylalanine.
➢ All aromatic amino acids are transported to the brain by the
Laromatic amino acid transporter in brain capillaries.
➢ Therefore, phenylalanine accumulates and crowds out tryptophan at
the L-aromatic amino acid transporter hindering its transport to the
brain cells
➢ Since tryptophan is the precursor of the serotonin, an important
neurotransmitter in the brain, competitive inhibition of its transport
results in lack of cerebral serotonin which leads to cognitive and
neurological deficits that occur by the age one year if untreated
➢ The disease can also be caused by reduced affinity of phenylalanine
hydroxylase for its cofactor, tetrahydrobiopterin. In such cases,
treatment involves increased dosages of tetrahydrobiopterin.
1
, ➢ Dietary phenylalanine can also be limited to manage the disease
2. Alkaptonuria / Black urine disease❖This is also a defect of
phenylalanine-tyrosine pathway involving the deficiency in the
enzyme homogentisate 1, 2-dioxygenase, an enzyme catalyzing the
oxidation of homogentisate.
❖This leads to accumulation of homogentisate which is then excreted
in urine.
❖The urine containing homogentisate turns dark when exposed to
open air due to an oxidization process causing homogentisate to
polymerize forming melanin-like substance.
❖This disorder is relatively benign and causes no serious ill effects
since excess homogentisate is easily excreted in urine.
2
➢ 1. Phenylketonuria (PKU)/ Hyperphenylalaninemia
➢ It results due to homozygous defect of phenylalanine hydroxylase
resulting into accumulation of phenylalanine.
➢ All aromatic amino acids are transported to the brain by the
Laromatic amino acid transporter in brain capillaries.
➢ Therefore, phenylalanine accumulates and crowds out tryptophan at
the L-aromatic amino acid transporter hindering its transport to the
brain cells
➢ Since tryptophan is the precursor of the serotonin, an important
neurotransmitter in the brain, competitive inhibition of its transport
results in lack of cerebral serotonin which leads to cognitive and
neurological deficits that occur by the age one year if untreated
➢ The disease can also be caused by reduced affinity of phenylalanine
hydroxylase for its cofactor, tetrahydrobiopterin. In such cases,
treatment involves increased dosages of tetrahydrobiopterin.
1
, ➢ Dietary phenylalanine can also be limited to manage the disease
2. Alkaptonuria / Black urine disease❖This is also a defect of
phenylalanine-tyrosine pathway involving the deficiency in the
enzyme homogentisate 1, 2-dioxygenase, an enzyme catalyzing the
oxidation of homogentisate.
❖This leads to accumulation of homogentisate which is then excreted
in urine.
❖The urine containing homogentisate turns dark when exposed to
open air due to an oxidization process causing homogentisate to
polymerize forming melanin-like substance.
❖This disorder is relatively benign and causes no serious ill effects
since excess homogentisate is easily excreted in urine.
2
