Mixed-function oxidases activity regulation

Woods JS, Carver GT, Fowler BA (1979) Altered regulation of hepatic heme metabolism by indium chloride. Toxicol Appl Pharmacol 49 455-461 Woods JS, Fowler BA, Eaton DL (1984) Studies on the mechanisms of thallium mediated inhibition of hepatic mixed-function oxidase activity correlation with inhibition of NADPH-cytochrome c (P-450) reductase. Biochem Pharmacol 33 571-576... 

Gelboin, H. (1980) Benzo[a]pyrene metabolism, activation, and carcinogenesis Role and regulation of mixed functional oxidases and related enzymes. Physiol. Rev. 60, 1107-1166. 

There are two hepatic vitamin D 25-hydroxylases, the major one in the mitochondria and the other in the smooth endoplasmic reticulum (Figure 37-2). Both require NADPH and molecular oxygen. The microsomal enzyme appears to be a P-450 mixed-function oxidase. 25-Hydroxylase activity also occurs in intestine, kidney, and lung. 25-Hydroxylase is apparently regulated only by availability of its substrate, leading to a high plasma concentration of 25-(OH)D and a low concentration of vitamin D. 

Regulation of the dietary intake of amino acids can also be important when considering the treatment of certain defects in amino add biosynthesis. Phenylalanine is an essential amino acid that is also used to generate the nonessential amino add tyrosine. The enzyme that carries out this readion is the mixed function oxidase phenylalanine hydroxylase (PAH). Inherited deficiencies in PAH are associated with a condition known as phenylketonuria (PKU see Case 38). The absence of PAH results in elevations of phenylalanine and various phenylketones, the accumulation of which is associated with the neurologic defects seen in this disorder. PKU can be treated by controlling the dietary intake of phenylalanine. Diets low in phenylalanine will help prevent excessive elevations in phenylalanine. Phenylalanine can not be completely eliminated from the diet because it is an essential amino acid needed for protein synthesis. In the absence of PAH activity, tyrosine becomes an essential amino add because it cannot be generated from phenylalanine. 

Tyrosine hydroxylase is an iron-containing mixed function oxidase that utilizes tetrahydrobiopterin, oxygen, and L-tyrosine as cosubstrates. Molecular oxygen is transferred from O2 to the aromatic ring of tyrosine. In recent years the molecular properties and the mechanisms that regulate the activity of this enzyme have been studied in depth by several laboratories (Kuhn and Lovenberg, 1983). 

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