Pathways

20-hydroxyecdysone is a steroid hormone that controls the ecdysis or molting of insects. It is formed from the modification of cholesterol by various p450 enzymes. Initially, cholesterol is modified by a cholesterol 7-desaturase, forming 7-dehydrocholesterol. In the endoplasmic reticulum, 7-dehydrocholesterol is modified by cytochrome p450 307a1 to form diketol. Diketol can interact with the cytochrome p450 306a1 enzyme, ecdysteroid 25-hydroxylase, forming 2,22-dideoxy-3-dehydroecdysone. In the mitochondria, 2,22-dideoxy-3-dehydroecdysone can be modified by cytochrome p450 302a1, also known as ecdysteroid 22-hydroxylase, which forms 3-dehydro-2-deoxyecdysone, which in turn can be modified by cytochrome p450 315a1, ecdysteroid 2-hydroxylase, to form 3-dehydroecdysone, one of the final products of this pathway. Diketol can also spontaneously form 3β,5β-ketodiol, which then interacts with the same enzymes as diketol. First, it is modified in the endoplasmic reticulum by cytochrome p450 306a1, ecdysteroid 25-hydroxylase to form 3β,5β-ketotriol. In the mitochondria, 3β,5β-ketotriol is then modified by cytochrome p450 302a1, ecdysteroid 22-hydroxylase, to form 2-deoxyecdysone, and then cytochrome 315a1, ecdysteroid 2-hydroxylase, to form ecdysone. From this point, ecdysone can interact with ecdysone oxidase to form 3-dehydroecdysone, the same product as in the first half of this pathway. In addition to this reaction, ecdysone can also interact with ecdysone 20-monooxygenase in the mitochondria to form 20-hydroxyecdysone (crustecdysone), which is the main molting hormone. Finally, 20-hydroxyecdysone can interact with cytochrome p450 18a1, 26-hydroxylase, in order to form 20,26-dihydroxyecdysone, the final product of this branch of the pathway.

Molybdenum cofactor biosynthesis is a pathway that begins in the mitochondrial matrix and ends in the cytosol by which GTP becomes molybdenum cofactor, a metal-containing prosthetic group common to nearly all molybdoenzymes. Such molybdenum enzymes play important roles in the regulation of the nitrogen, sulfur and carbon cycles . First, the enzyme GTP 3',8-cyclase, located in the mitochondrial matrix, catalyzes the conversion of GTP, S-adenosylmethionine, and a reduced electron acceptor to 3′,8-cH2GTP, L-methionine, 5'-deoxyadenosine, an oxidized electron acceptor, and a hydrogen ion with the help of a [4Fe-4S] cluster cofactor. Second, cyclic pyranopterin monophosphate (cPMP) synthase catalyzes the conversion of 3′,8-cH2GTP to cPMP and pyrophosphate. Next, ABC transporter of the mitochondrion 3 (ATM3) exports cPMP from the mitochondrial matrix into the cytosol where it is acted upon by molybdopterin (MPT) synthase. MPT synthase is a heterotetramer composed of 2 large and 2 small subunits. The two small subunits are thiocarboxylated by molydopterin synthase sulfurtransferase, and each transfers a sulfur to cPMP to generate the dithiolene in molybdopterin and releasing hydrogen ion in the process. The following enzyme in the pathway, molybdenum insertase is a two-domain protein that catalyzes the fourth and fifth reactions. The smaller C-terminal Cnx1G domain functions as a molybdopterin molybdotransferase and activates molybdopterin for molybdenum insertion. The product of this reaction, molybdopterin adenine dinucleotide (MPT-AMP), is then transferred to the larger N-terminal Cnx1E domain which exhibits molybdopterin adenylyltransferase activity and inserts molybdenum into the dithiolene of molybdopterin, creating molybdenum cofactor (Moco). Molybdenum insertase requires a divalent cation (e.g. magnesium) as a cofactor.

Molybdenium cofactor deficiency (Sulfite oxidase deficiency) is caused by mutations in the genes MOCS1 and MOCS2 in the formation of molybdenum cofactor. A molybdenum-containing cofactor is essential to the function of 3 enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Xanthine dehydrogenase is a molybdenum-containing hydroxylase involved in the oxidative metabolism of purines. Defects in this enzyme cause accumulation of hypoxanthine,, s-s-sulfocysteine, taurine, and xanthine in the urine. Symptoms include hemorrhage, cerebral atrophy, encephalopathy, lactic acidosis, nystagmus, spastic diplegia/quadriplegia, and vomiting.

Molybdenium cofactor deficiency (Sulfite oxidase deficiency) is caused by mutations in the genes MOCS1 and MOCS2 in the formation of molybdenum cofactor. A molybdenum-containing cofactor is essential to the function of 3 enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Xanthine dehydrogenase is a molybdenum-containing hydroxylase involved in the oxidative metabolism of purines. Defects in this enzyme cause accumulation of hypoxanthine,, s-s-sulfocysteine, taurine, and xanthine in the urine. Symptoms include hemorrhage, cerebral atrophy, encephalopathy, lactic acidosis, nystagmus, spastic diplegia/quadriplegia, and vomiting.

Molybdenium cofactor deficiency (Sulfite oxidase deficiency) is caused by mutations in the genes MOCS1 and MOCS2 in the formation of molybdenum cofactor. A molybdenum-containing cofactor is essential to the function of 3 enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Xanthine dehydrogenase is a molybdenum-containing hydroxylase involved in the oxidative metabolism of purines. Defects in this enzyme cause accumulation of hypoxanthine,, s-s-sulfocysteine, taurine, and xanthine in the urine. Symptoms include hemorrhage, cerebral atrophy, encephalopathy, lactic acidosis, nystagmus, spastic diplegia/quadriplegia, and vomiting.

Molybdenium cofactor deficiency (Sulfite oxidase deficiency) is caused by mutations in the genes MOCS1 and MOCS2 in the formation of molybdenum cofactor. A molybdenum-containing cofactor is essential to the function of 3 enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Xanthine dehydrogenase is a molybdenum-containing hydroxylase involved in the oxidative metabolism of purines. Defects in this enzyme cause accumulation of hypoxanthine,, s-s-sulfocysteine, taurine, and xanthine in the urine. Symptoms include hemorrhage, cerebral atrophy, encephalopathy, lactic acidosis, nystagmus, spastic diplegia/quadriplegia, and vomiting.