https://www.amjmed.com/article/0002-9343(63)90089-5/pdf

Biochemical, pathologic and clinical aspects of alcaptonuria, ochronosis and ochronotic arthropathy: Review of world literature (1584–1962)

The phenylalanine hydroxylating system from mammalian liver.

As implied by the title, this review of phenylketonuria (PKU) will be neither comprehensive nor encyclopedic. Rather, it will be limited to those aspects of the disease where sufficient biochemical knowledge is available to support meaningful discussion—admittedly, often speculative—about underlying mechanisms. Recent comprehensive reviews are available (Hsia, 1970; Knox, 1972).

Phenylketonuria: Biochemical Mechanisms

Publisher Summary The chapter discusses the metabolism of phenylalanine, tyrosine, and tryptophan. Phenylalanine acid tryptophan is “essential” amino acids for higher organisms— that is, they cannot be synthesized by the organism and must be supplied in the diet. Tyrosine, formed from phenylalanine acid is not essential if the phenylalanine intake is adequate. The chapter presents biosynthesis, which is confined to lower organisms (bacteria, fungi, plants, etc.). Shikimic acid is a common precursor of the aromatic amino acids and of the bacterial growth factors, p-amino- and p-hydroxybenzoic acids. Phenylalanine and tyrosine are metabolized in higher organisms by two routes, which are quantitatively less important but physiologically of the highest importance. The first leads to the adrenal hormones adrenaline (epinephrine) and nonadrenaline (norepinephrine); this pathway also leads to melanin. The second leads to the thyroid hormones thyroxine and triiodothyronine, the synthesis and breakdown of which are also discussed. Tryptophan is metabolized in a wide range of organisms by a pathway involving: an unknown intermediate, formylkynurenine, kynurenine, hydroxykynurenine (or its phosphate), hydroxyanthranilic acid (or its phosphate), two unknown intermediates, and nicotinic acid. The relation of other vitamins to the pathway, side reactions giving such substances as anthranilic acid, kynurenic acid, and xanthurenic acid and the further degradation of nicotinic acid and its relation to the pyridine nueleotides are also considered. Tryptophan also gives rise to the important plant hormone, indoleacetic acid, and micro-organisms and especially plants metabolize the aromatic amino acids to a wide range of natural products, for example, certain antibiotics, alkaloids, flavonoids, and possibly lignin.

A.J. Wakeman

Papers

The Catabolism of Phenylalanine, Tyrosine and of their Derivatives