Oxidase enzymes Subject

Superoxide is formed (reaction 1) in the red blood cell by the auto-oxidation of hemoglobin to methemo-globin (approximately 3% of hemoglobin in human red blood cells has been calculated to auto-oxidize per day) in other tissues, it is formed by the action of enzymes such as cytochrome P450 reductase and xanthine oxidase. When stimulated by contact with bacteria, neutrophils exhibit a respiratory burst (see below) and produce superoxide in a reaction catalyzed by NADPH oxidase (reaction 2). Superoxide spontaneously dismu-tates to form H2O2 and O2 however, the rate of this same reaction is speeded up tremendously by the action of the enzyme superoxide dismutase (reaction 3). Hydrogen peroxide is subject to a number of fates. The enzyme catalase, present in many types of cells, converts... 

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

The enzymes involved in the polyamine metabolic pathway have been the subject of intensive study, and a number of specific inhibitors for these enzymes have been designed as potential antitumor or antiparasitic agents [166]. Thus, a-difluoromethylornithine, has become a clinically useful agent [167]. Most of the studies involving inhibitors of polyamine metabolism have focused on enzymes involved in the biosynthetic pathway. Recently, there has been considerable interest generated in the enzyme spermidine/spermine-hT -acetyltrans-ferase enzyme (SSAT), the rate-limiting step in the back conversion of polyamines. SSAT, in conjunction with polyamine oxidase (PAO), allows for reversal of the biosynthetic pathway and attenuation of the levels of individual polyamines. 

Most phase one reactions are catalyzed by the drug-metabolizing enzymes (mixed function oxidases, oxygenases) located in the endoplasmic reticulum of liver and, to a lesser extent, in intestine, kidney, and lung. These enzymes have been the subject of intensive research (G7, G8, LI). 

The biochemical model contains the pathways of the enzymatic reactions in the synthetic routes. Model can be constructed for each alkaloid. Eigure 75 presents biochemistry model of Catharantus alkaloids. The most important enzymes on this model are TDC (tryptophan decarbocylase), GlOH (geraniol 10-hydroxylase) and SS (strictoside synthase). NADPH+, PO (Peroxidase), O (oxidase) and NADH+ are all active in different Catharantus alkaloid formations. The biochemical models are subject to both qualitative and quantitative alkaloid... 

CGD) Defect due to mutation in neutrophil enzyme NADPH oxidase gene coding for any one of the four subunits of the enzyme Patients subject to recurrent infections by catalase-positive organisms and to granuloma formation X-Unked mutation more severe... 

Polyphenol oxidase (PPO) (EC 1.14.18.1 monophenol monooxygenase [tyrosinase] or EC 1.10.3.2 0-diphenol 02-oxidoreductase) is one of the more important enzymes involved in the formation of black tea polyphenols. The enzyme is a metallo-protein thought to contain a binudear copper active site. The substance PPO is an oligomeric particulate protein thought to be bound to the plant membranes. The bound form of the enzyme is latent and activation is likely to be dependent upon solubilization of the protein (35). PPO is distributed throughout the plant (35) and is localized within in the mitochondria (36), the cholorplasts (37), and the peroxisomes (38). Using antibody techniques, polyphenol oxidase activity has also been localized in the epidermis palisade cells (39). Reviews on the subject of PPO are available (40—42). 

MAO-A (isoform A) is the amine oxidase primarily responsible for norepinephrine, serotonin, and tyramine metabolism. MAO-B is more selective for dopamine. The irreversible inhibitors available in the USA are nonselective and block both forms of the enzyme. Irreversible block of MAO, characteristic of the older MAO inhibitors, allows significant accumulation of tyramine and loss of the first-pass metabolism that protects against tyramine in foods. As a result, the irreversible MAO inhibitors are subject to a very high risk of hypertensive reactions to tyramine ingested in food. 

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