Type of bio-transformation reaction.

. Bio reactions in the liver can be divided into four reaction types: oxidation, reduction, hydrolysis, and conjugation.(i) Oxidation reaction 1. Particulate oxidase systemparticle oxidase system occupies an important position in the oxidation reaction of biological transformation. It is an oxidase system that requires cytochrome P450, which activates molecular oxygen directly, so that an oxygen atom is added to the active molecule, so it is called monooxygenase. Because in the reaction an oxygen atom is mixed into the body, and an oxygen atom oxidizes NADPH to produce water, that is, an oxygen molecule plays two functions, so it is also known as mixed functional oxidase (mixed function oxidase). It can also be called hydroxylase. The specificity of the monooxygenase system is poor, which can catalyz a variety of
different types
different types of oxidation reactions.(1) the composition of the monooxygenase systemthe addition of monooxygenase system consists of NADPH, NADPH cytochrome P450 reductase and cytochrome P450. NADPH-cytochrome P450 reductase is supplemented by FAD and FMN. The ratio is 1:1. The cytochrome P450 is a b-family cytochrome based on the ferrogen IX, which contains the parts that bind to oxygen and the action.(2) plus monooxygenase system reaction processadd monooxygenase system catalytic total reaction type is as follows: NADPH, H, O2, RH→NADP, H2O, ROH reaction, the action oxidation to produce hydroxylides. Cytochrome P450 contains a single hemohemolytic co-base and can only accept one electron, while NADPH is a two-electron supply, and NADPH-P450 reductase is both a two-electron recipient and an electron-supply. Just communicate this electronic delivery chain. The steps of oxidation of the active body by the addition of monooxygenase system are shown in Figure 11-2.Figure 11-1 Oxidation and also prototype FAD and FMNFigure 11-2 plus monooxygenase system reaction process (3) plus monooxygenase system physiological significance and function characteristics After hydroxylation, the water solubility of the drug or poison can be enhanced, which is beneficial for excretion. Such as toluene as a commonly used chemical raw materials, in the liver by oxygenation hydroxylation to produce a pair of -foric acid, polarity enhancement, easy to excrete. In addition, vitamin D3 hydroxylation is biologically active 25-(OH)D3.plus monooxygenase can induce the generation, such as phenytobidol drugs can induce the synthesis of monooxygenase, long-term use of such drugs in patients, isoprene barbito, aminobilin and other drugs conversion and tolerance is also enhanced.. 2. Mitochondrial monoamine oxidase system amine oxidase belongs to the velasin enzyme class, which is found in mitochondrials and can catalyz histamines, tyrosamines, body amines, rotten amines and other intestinal corruption products oxidizing deamine to produce the corresponding aldehyde. For example:3.
dehydrogenase
-seriescell fluid contains NAD-plus coenzyme alcohol dehydrogenase and aldehyde dehydrogenase, respectively, catalytic alcohol or aldehyde dehydrogenation, oxidation to produce the corresponding aldehyde or
acid
. Such as:(ii) reduction reaction liver particles exist by NADPH and also prototype cytochrome P450 hydrogen-supplying reductase, mainly nitrophase and anitrogen reductase, are yellow
protease
class. The product of the reduction is amine. For example, nitrobenzene is hydrogenated to produce aniline under nitrobenzene catalysis, and anitrobenzene is reduced to produce aniline under anitriumase catalysis. In addition, the hypnotic drug triclosal acetaldehyde can also be reduced in the liver to produce triclosal ethanol and lose its hypnotic effect.(iii) Hydrolysis reactionsvarious hydrolyzed enzymes in liver cells. Such as esterase, alamide enzyme and glycoside enzyme, respectively, hydrolyzed a variety of ester bonds, alamide bonds and glycoside bonds. Widely distributed, hydrolyzed enzymes in the human liver can catalyz hydrolysis of acetylamine, prucain, lidokain and simple adipose esters. For example (iv) binding reaction is most important biological transformation in the body. Non-nutritional substances containing hydroxyl, carboxy or amino, which combine with a more polar substance in the liver, increase water solubility, but also mask the original functional group on the action, generally have detoxifying function. Some non-nutrients can be directly combined, while others are oxidized, reduced, hydrolysed and then combined. The binding reaction can be carried out in the particles, cell fluids and mitochondrials of liver cells. the binding agents participating in the reaction can be divided into a variety of reaction types: 1. Glucoalic acid binding reaction Glucoalic acid binding is the most important and universal binding method. U.S. phosphate glucosalic acid (UDPGA) is an active supply of glucosalic acid, which is produced by the glycoalic acid cycle. UDP glucosalic acid
transorase
is found in the hepatocellular particles, which transfers glucose aldehyde acid to hydroxy, amino and carboxyl of poisons or other active substances to form glucosalate glycosides. After binding, its toxicity is reduced and it is easy to excrete. Bilirubin, steroids
hormones
, morphine, phenybarbital drugs, etc. can be combined with glucosalic acid in the liver for biotransformation. Clinically, the treatment of liver disease with glucose aldehyde acid preparations (e.g. liver thaile) is based on the principle of enhancing the biotransformation function of the liver. . 2. Sulphuric acid binding reaction with 3' - adenosine phosphate 5' - phosphate sulfuric acid (PAPS) as an active sulphuric acid supply, in the liver cell cell fluid has sulphuric acid transferase, can catalytically transfer the sulfate root in PAPS to steroids, phenol hydroxyl, the generation of sulfate. Estrogen binds to sulphuric acid in the liver and insulates. . 3. Acetyl-based binding reaction In catalyzed by acetyl-based transferase, acetyl-based acetyl-based acetyl-based acetyl-based feeder is formed in combination with aromatic amine-like
compounds
to produce the corresponding acetylated derivatives. Such as sulfonamide drugs and anti-tuberculosis drug isoniazid in the liver by acetylation and lost effect. 4. Methyl binding reaction Hepatocellular fluids and particles have a variety of transmethylase, containing hydroxyl, or amino compounds can carry out methylation reaction, methyl supply is S adenosine methionine (SAM). For example, nicolamide can be methylated to produce N methylaide. . 5. Glycine binding reaction Some poisons, drugs of the carboxyl and coenzyme A binding to form ayl Kievase A, in the acrylic CoA:
amino acid
N-amyl transferase catalysis with glycine binding, the production of the corresponding binding products. Such as the production of horse uric acid. can be seen from above, the bio-transformation of the liver is very wide- and wide-ranging. Many toxic substances into the human body quickly concentrated in the liver detoxification, which is on the one hand, but on the other hand, it is precisely because these harmful substances easily gather in the liver, if the amount of poison is too much, but also easy to poison the liver itself, therefore, for liver disease patients, to limit the use of drugs mainly in the liver detoxification, so as not to poison. biorefract reactions listed above include drugs, poisons or corrupt products that are converted to less toxic or biological activity. However, some substances are enhanced by bio-transformation, their activity or toxicity, i.e. not inactivated but activated. Such as benzodia (carcinogens) in the liver after bio-transformation to form the final carcinogen. there are also carcinogens in the body there are a variety of conversion methods, some are carcinogenic (active), some are detoxifying, such as aflatoxin B1 bio-transformation.
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