Protein Metabolism

Glycolysis &
Citric Acid Cycle
Lipid Metabolism &
Review Metabolism
 Elmhurst College
Transamination Urea Cycle Energy Summary  Chemistry Department
Oxidative Deamination Bilirubin - Heme Catabolism  PKU  Virtual ChemBook

PKU and Other Errors in Phenylalanine Metabolism


The most frequent defects in amino acid metabolism involve the amino acids phenylalanine and tyrosine. Numerous enzymes are required to convert phenylalanine into a variety of biochemical products. The metabolism of phenylalanine and the various metabolic blocks are illustrated in graphic on the left where for simplicity, many intermediate steps have been omitted. The circled letters indicate enzyme defects which will of course disrupt the reactions which follow it.

A. Phenylketonuria (PKU)

If the enzyme which converts phenylalanine into tyrosine is missing,
then phenylalanine undergoes a transamination reaction to make
phenylpyruvic acid instead.

Phenylpyruvic acid can be found in the urine when excessive levels have built up. If untreated, mental retardation effects are evident by the first year along with other symptoms which include: unusual irritability, epileptic seizures and skin lesions. Since the defect is found in 1 in 20,000 births, a general screening program (PKU Test) has been mandated in many states and is routinely made several days after the birth of an infant. The defective metabolism can only be controlled by a diet containing small amounts of phenylalanine.

Link to Chime: Phenylalanine Hydroxylase - Department of Biochemistry,The University of Arizona


B. Goitrous Cretinism:

Hypothyroidism results from the absence of an enzyme to incorporate iodine into tyrosine in the first step in the synthesis of thyroxine. The result is stunted growth, lethargy, course hair, poor muscle tone and other facial defects. Hypothyroidism is treated by administration of thyroid extract.

C. Albinism:

The biochemical defect in albinism appears to be the absence of the enzyme tyrosinase, which prevents the synthesis of melanin pigment by pigment-forming cells. These individuals have a very white skin, fine white hair, pink or light blue irises of the eyes, and a variety of other eye disturbances. Various types of localized albinism are characterized by the absence of pigment in specific parts of the body. There is no treatment for albinism.


D. Tyrosinosis:

Accumulation of p-hydroxyphenylpyruvic acid usually leads to an enlargement of the liver and spleen. Death results from liver failure between 4 months and 5 years of age. Diet control may help in reducing the symptoms of tyrosinosis.

E. Alkaptonuria:

Alkaptonuria occurs when the absence of an enzyme prevents the breakdown of homogentisic acid. A large amount of homogentisic acid excreted in the urine causes it to turn black upon exposure to air. Other characteristics of alkaptonuria include arthritis and pigmentation of cartilage. It was this relatively benign disease that was first used as the basis for the concept of inborn errors of metabolism.