Hydroxy dehydrogenase

L-2-Hydroxy glutaric aciduria L-2-Hydroxy dehydrogenase (Duranin)... 

In addition to the protective effect of 17a-alkylation, methyl substitution in positions 1,2, and 6 and the position of unsaturation in ring A also have an important influence on the relative activity of 17/3-hydroxy-dehydrogenase [5]. The relative activities of 17/3-hydroxy-5a-androstan-... 

Defective Bile Acid Synthesis. Specific defects in bile acid synthesis have long been postulated. Two inborn errors of bile acid synthesis, both associated with idiopathic neonatal hepatitis, A -3-oxosteroid 5-P-reductase deficiency and 3-p-hydroxy-dehydrogenase isomerase deficiency, have been described. A third disorder associated with defective bile... 

The reverse reaction has also been noted, i.e. the formation of PGE compounds from prostaglandins of the F series. This reaction is catalysed by an enzyme different from the 9-keto reductase, prostaglandin 9-hydroxy dehydrogenase [325-327], In vivo, this reaction may take place to a considerable extent in certain species, for example the rat and the guinea pig [281], whereas it seems to be of minor importance in others, such as the human [274,280,281]. 

Before being excreted into urine, TXB2 is degraded mainly by 8-oxidation. The major urinary metabolite was identified as dinor-TXB in the guinea pig, monkey and man, [188-192,194,195] in the rat, however, the major product was tetranor-TXB2 [193]. In the simian and human species, a number of additional metabolites were identified [190,195], which have been formed by various combinations of well-known metabolic reactions such as jS-oxidation and w-oxidation. Several metabolites, however, had the saturated keto structure in the side chain, and it was proposed that some of the break-down products were better substrates for the 15-hydroxy dehydrogenase than TXBj itself, or alternatively, that any formed... 

The metabolic fates of TXA2 thus seem to be very complicated. A few years ago, TXB2 was almost automatically considered the end product of TXAj formation and a reliable parameter for monitoring thromboxane biosynthesis. Now it has become clear that under many circumstances it is only a minor and insignificant product. TXAj seems to be metabolized partially via different pathways and forms covalent derivatives with proteins, or is converted via the 15-hydroxy dehydrogenase pathway. The further fates of these products are not known. It is also possible that thromboxane formed in different cell types may undergo different fates. 

The intermediate steps in the formation of estrogens in human placenta have not yet been established, but it is possible that they go through the following sequence after hydrolysis dehydroepiandrosterone, by action of a 3 -hydroxy dehydrogenase, is —" isomerase (very considerable in pla-... 

As a result of the prolongation of the deficiency of the 3/3-hydroxy-dehydrogenase, As — A isomerase system after birth, an important quantity of 3 -hydroxy-As steroids is excreted in the urine of newborns. As the 16a-hydroxylase is very active in the first days of life, very little if any dehydroepiandrosterone or dehydroepiandrosterone sulfate is excreted in newborn urine (Migeon et al., 1957b Vestergaard, 1965 Bertrand et al., 1966 Paulsen et al., 1966) on the other hand, the total excretion rate of urinary 16a-hydroxydehydroepiandrosterone is 300-600 )tig/24 hours (Bongiovanni, 1962 Mitchell and Shackleton, 1966 Mitchell, 1967). Cleary and Pion (1968) found these values to be between 0.7 and 3 mg/24 hours in the first 2 days of life. Alost of these steroids arc eliminated as ester sulfates. 

Although alcohol dehydrogenases (ADH) also catalyze the oxidation of aldehydes to the corresponding acids, the rate of this reaction is significantly lower. The systems that combine ADH and aldehyde dehydrogenases (EC 1.2.1.5) (AldDH) are much more efficient. For example, HLAD catalyzes the enantioselective oxidation of a number of racemic 1,2-diols to L-a-hydroxy aldehydes which are further converted to L-a-hydroxy acids by AldDH (166). 

Hydroxy butyrate dehydrogenase (from Rhodopseudomonas spheroides) [9028-38-0] Mf 85,000, [EC 1.1.1.30], amorphous. Purified by two sequential chromatography steps on two triazine dye-Sepharose matrices. [Scavan et al. Biochem J 203 699 7952.]... 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

Ketone body synthesis occurs only in the mitochondrial matrix. The reactions responsible for the formation of ketone bodies are shown in Figure 24.28. The first reaction—the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA—is catalyzed by thiolase, which is also known as acetoacetyl-CoA thiolase or acetyl-CoA acetyltransferase. This is the same enzyme that carries out the thiolase reaction in /3-oxidation, but here it runs in reverse. The second reaction adds another molecule of acetyl-CoA to give (i-hydroxy-(i-methyl-glutaryl-CoA, commonly abbreviated HMG-CoA. These two mitochondrial matrix reactions are analogous to the first two steps in cholesterol biosynthesis, a cytosolic process, as we shall see in Chapter 25. HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction. This reaction is mechanistically similar to the reverse of the citrate synthase reaction in the TCA cycle. A membrane-bound enzyme, /3-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to /3-hydroxybutyrate. 

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

Most of the acetyl-CoA formed by 3-oxidation in liver is converted to acetoacetate by the 3-hydroxy-3-methylglutaryl-CoA pathway (Guzman and Gelen, 1993). Acetoacetate is reversibly converted to D-3-hydroxybutyrate by D-3-hy-droxybutyrate dehydrogenase in the mitochondrial matrix in all tissues. 

In a related approach, Adam ef al. used glycolate oxidase with D-lactate dehydrogenase for the deracemization of a wide range of racemic a-hydroxy acids (20) (Figure 5.13) [23]. 

An impressive indication of the high regioselectivity of hydroxysteroid dehydrogenases (HSHDs) was reported for the oxidation of various hydroxyl groups at the steroid core ofbile acids [26] (Scheme 9.1). The hydroxy-substituents at positions 3, 7, and 12 could be selectively addressed depending on the hydroxysteroid... 

There is no associated impairment of hydroxyprohne catabolism. The metabolic block in type II hyperpro-linemia is at glutamate-7-semiaIdeliyde dehydrogenase, which also functions in hydroxyprohne catabolism. Both proline and hydroxyprohne catabohsm thus are affected and A -pyrroline-3-hydroxy-5-carboxylate (see Figure 30-10) is excreted. 

Trichloroethylene 1.9 OS-phosphate buffer pH 7 (2/1) 20 /S-Hydroxy steroid dehydrogenase... 

---