PKU - phenylketonuria

PKU - Phenylketonuria

(1) PKU means phenylketonuria which is an autosomal recessive inborn error metabolism of due to phenylalanine does not occur deficiency of phenylalanine hydroxylase (PAH) enzyme. 

 2 ) In this disorder the metabolism of phenylalanine does not occur due to deficiency of phenylalanine hydrolase

( 3 ) This enzyme necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine . 

 4) When PAH activity is reduced, phenylalanine accumulates in blood and cerebrospinal fluid and is converted into phenylpyruvate or phenyl-ketone which is a toxic compound. This may cause mental retardation. Excess phenylalanine is excreted in urine, hence this disease is called phenylketonuria. 

 ( 5 ) PKU is caused by mutations in the PAH gene on chromosome no . 12. 

 6) Untreated PKU causes abnormal phenotype which includes growth failure, poor skin pigmentation, microcephaly, seizures, global developmental delay and severe intellectual impairment. However , at birth if an infant is checked for PKU , the further abnormalities can be avoided

What is phenylketonura ?

Phenylketonuria (PKU)  is a genetic

error of protein metabolism characterized by elevated blood

levels of the amino acid phenylalanine. Most children with phenylketonuria have a mutation in the gene that codes for the enzyme phenylalanine hydroxylase, the enzyme needed to convert

phenylalanine into the amino acid tyrosine, which can enter the

Krebs cycle . Because the enzyme is deficient, phenylalanine cannot be metabolized, and what is not used in protein synthesis builds up in the blood. If untreated, the disorder causes

vomiting, rashes, seizures, growth deficiency, and severe mental re-

tardation. Newborns are screened for PKU, and mental retardation can be prevented by restricting the affected child to a diet that supplies only the amount of phenylalanine needed for growth, although learning disabilities may still ensue. Because the artificial

sweetener aspartame (NutraSweet) contains phenylalanine, its con-

sumption must be restricted in children with PKU. 

• The relationship of genes to heredity is illustrated by examining

the alleles involved in a disorder called phenylketonuria (PKU)

(fen-il-ke¯-toˉ-NOO-re¯-a). People with PKU  are unable to manufacture

the enzyme phenylalanine hydroxylase. The allele that codes for phenylalanine hydroxylase is symbolized as P; the mutated allele that fails to produce a functional enzyme is represented by p. The which shows the possible combinations of gametes from two parents who each have one P and one p allele,is called a Punnett square. In constructing a Punnett square, the

possible paternal alleles in sperm are written at the left side and the

possible maternal alleles in ova (or secondary oocytes) are written at the top. The four spaces on the chart show how the alleles can combine in zygotes formed by the union of these sperm and ova to produce the three different combinations of genes, or genotypes

(JE¯-noˉ-tı¯ps): PP, Pp, or pp. Notice from the Punnett square that 25% of the offspring will have the PP genotype, 50% will have the Pp genotype, and 25% will have the pp genotype. (These percentages are probabilities only; parents who have four children won’t

necessarily end up with one with PKU.) People who inherit PP or

Pp genotypes do not have PKU; those with a pp genotype suffer

from the disorder. Although people with a Pp genotype have one PKU allele (p), the allele that codes for the normal trait (P) masks the presence of the PKU allele. An allele that dominates or masks

the presence of another allele and is fully expressed (P in this example) is said to be a dominant allele, and the trait expressed is

called a dominant trait. The allele whose presence is completely

masked (p in this example) is said to be a recessive allele, and the

trait it controls is called a recessive trait.