Biotransformation[1]It refers to the metabolic process in which the chemical structure of poisons changes after enzyme catalysis, that is, the poisons undergo qualitative changes.Biotransformation is an important event that occurs before the elimination of poisons in organisms, and its typical outcome is the production of non-toxic or low toxic metabolites.Therefore, biotransformation was equated with detoxification.However, in many cases, the toxic metabolites produced by biotransformation can lead to tissue damage.The biological transformation at this time is called biological activation.Also known as poisoning.
Chinese name
Biotransformation
Foreign name
Biotransformation
Interpretation
Metabolic transformation of chemicals catalyzed by various enzymes
Biotransformation is also called "metabolic transformation".The chemical change process of foreign compounds in vivo under the catalysis of enzyme or non enzyme.Biotransformation can reduce the toxicity of foreign compounds and biodetoxify, and also increase the toxicity of some foreign compounds (biological activation), which is generally called the duality of biotransformation.For example, soil microorganisms can transform lindane intocarbon dioxideHowever, underwater microorganisms can transform inorganic mercury into methylmercury, which is more toxic.Biotransformation of organic matter The energy and material necessary to maintain biological life activities, artificial inert organic matter is generally difficult to be biotransformed and pollute the environment.The absorption, distribution and excretion process of chemical poisons in the body is called biological transport[1]。
The metabolic process of chemicals is called biotransformation.The liver is a living thingTransformationThe main organ ofHepatocytemicrosomeEnzymes related to biotransformation exist in the cytoplasm, mitochondria and other parts.Other tissues such as kidney, gastrointestinal tract, lung, skin and placenta can also undergo certain biotransformation, but liver is the most important and has the strongest biotransformation function.
Function of enzyme
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Enzymatic reaction is very important for organism.In the mild environment of organisms, most biological organic molecules are very stable,Non catalytic reactionThe speed of is usually very slow.Without the catalysis of enzymes, many chemical reactions and biological functions in cells cannot occur.Enzymes asBiocatalystIts most prominent characteristics are the efficiency of promoting reaction speed and the specificity of substrate.The efficiency and specificity of enzymes are two aspects of the same thing, and they are unified[2]。
Some foreign bodies can affect the activity of enzymes related to biotransformation in the body, which can be divided into two types: ① enzyme inhibition.Some foreign bodies can reduce the activity of some enzymes, thus reducing the metabolic rate of foreign bodies, prolonging their retention time in the body and enhancing their toxicity.for exampleParathionOfmetaboliteParaoxon can inhibit the hydrolysis of malathionCarboxylesterase, makemalathionThe hydrolysis rate of β - lactamase decreased and its toxicity increased. ②Enzyme induction.Some foreign bodies can induce the synthesis of enzymes related to biotransformation, thus promoting the metabolic rate of foreign bodies.The substance with this effect is calledInducer。for examplePhenobarbitalIt can be induced in rat liver as an inducerGlucuronic acidTransferases；Simultaneous application of phenobarbital and2-AcetaminofluoreneCan reduce or weaken the carcinogenic effect of the latter.
In the past, the experimental research of biotransformation mainly focused on animals, using in vivo or in vitro experimental methods.It was found that in various tissues of animalsmicrosomePart) has the strongest biological transformation ability;The result of transformation can eliminate or reduce the toxicity of some foreign matters, or transform them into substances that are easy to be discharged, so it was called detoxification.However, subsequent studies showed that the result of biotransformation was not completely the same. Some foreign bodies, such as 2-acetylaminofluorene (AAF, a pre carcinogen, i.e. inactiveCarcinogen）After biotransformation (includingMixed functional oxidaseCatalytic oxidation reaction and sulfation combination reaction) can be converted intobiological activityThe final carcinogen (sulfuric acid AAF), this phenomenon is called toxicity.
Reaction type
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IntrahepaticBiotransformation reactionIt can be mainly divided into the first phase reaction (oxidation reaction, reduction reaction, hydrolysis reaction) and the second phase reaction (combination reaction).
Factors affecting biotransformation are as follows:
BiologyTransformationIt is affected by various factors in vivo and in vitro, such as age, gender, liver disease and drugs.E.g. newbornBioinvertaseHypoplasia, lack of ability to transform drugs and poisons, easy to occur drugs andtoxinPoisoning, etc.Due to organ degeneration, the elderlyAminopyrineThe drug transformation ability of, Baotaisong, etc. is reduced, and the drug effect is strong after use, with large side effects.In addition, some drugs or poisons can induce the synthesis of invertase to enhance the biological transformation ability of the liver, which is calleddrug metabolismEnzyme induction.For example, long-term usePhenobarbitalIt can induce the synthesis of liver microsomal monooxygenase system, thus making the body resistant to phenobarbital hypnotics.At the same time, due to the poor specificity of monooxygenaseInductionEnhance drug metabolism and detoxification, such as treating digoxin poisoning with phenobarbital.Phenobarbital also induces udp glucuronic acid in liver microsomesTransferasesTherefore, it is clinically used to treat neonatal jaundice.On the other hand, because the transformation and metabolism of multiple substances in vivo are often catalyzed by the same enzyme system, when taking multiple drugs at the same time, they can compete for the same enzyme system and inhibit each other's biologyTransformation。Attention should be paid to clinical medication, for example, Baotaisong can inhibitDicoumarinWhen taken at the same time, the anticoagulant effect of dicoumarin is strengthened, which is prone to bleeding.
Biotransformation is characterized by diversity (the same substance is transformed through multiple reactions), continuity (the first and second two-phase reactions are carried out continuously), and duality (the toxicity of the substance may be weakened or enhanced after biotransformation, that is, detoxification and toxicity).[3]
Transformation classification
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The binding reactions in biotransformation can be divided into the following types due to different types of conjugates, and examples of various types of binding reactions are as follows:
Glucuronylation
HepatocytemicrosomeContains very activeGlucuronosyltransferase, which usesUridine diphosphate glucuronic acid(UDP glucuronic acid) as a donor, catalyzing the transfer of glucuronic acid groups to a variety ofPolarityGroup compounds (including drugs, poisons and hormones), such asphenol, alcoholamineandcarboxylic acidEtc., generating β-Glucuronic acidglycoside。
Biotransformation
Sulfation
Sulfation reaction is a part of human body's chemical defense system. At the same timeChemical carcinogenIt plays an important role in biological activation.
Biotransformation
Methylation
Methylation refers to the reaction of active methyl compounds (e.gS-adenosylmethionine）The process of catalytic transfer of methyl to other compounds.It can form various methyl compounds, or carry outchemical modificationMethylation products are formed.
Biotransformation
Acetylation
Acetylation means that the nitrogen, oxygencarbon atomUp lead inAcetylCH3CO reaction.
The biotransformation of any kind of foreign matter will never be simple and uniform;They can carry out different oxidation-reduction or hydrolysis reactions at the same time, and then continue to carry out different types of binding reactions.In addition, nutritional conditions, hormone function, age, race, and individual differences all have significant effects on transformation mode.
Conversion process
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Biotransformation
Biotransformation is generally divided into two continuous processes, I and II. In process I, foreign matters are changed by oxidation, reduction or hydrolysis under the catalysis of relevant enzyme systemsChemical structure, forming certain activitiesGroup(such as - OH, - SH, - COOH, - NH2, etc.) or further expose these active groups.In process II, the first level of foreign mattermetaboliteUnder the catalysis of other enzyme systems, some compounds in the cell are combined with the above active groups to generate binding products (secondary metabolites).combinationproductPolarity of（Hydrophilicity）It is generally enhanced to facilitate drainage, such asCarbamate insecticideAmine naphthalene（Carbaryl）The biotransformation process of is as follows:
Generally, the biotransformation of foreign bodies has to go through these two continuous processes, but some foreign bodies have their own corresponding active groups, so they can directly combine with the substances in the cells without going through process I to complete their biotransformation.
oxidation reaction
Biotransformation
The oxidation reaction in the process of foreign body biotransformation I isMixed functional oxidaseSystem (also called monooxygenase systemhydroxylaseDepartment orCytochrome P-450Enzyme system)CatalysisUnder.The oxidation of foreign matters can be expressed as follows:
NADPH2: prototype reductioncoenzyme II；NADP: Oxidative coenzyme II is an enzyme system with strong activity, but poor specificityLiposolubilityAlmost all of the foreign matters in the oil can be oxidized under its catalysis, so it is often called mixed functional oxidase.Think it can catalyzeoxidation reaction As shown in the table.
Hydrolysis reaction in biotransformation process I is the transformation mode of esters, amides and other foreign matters.Organophosphorus pesticideChemically, it belongs to esters or amides, so it is composed of corresponding hydrolases (such as esteraseAmidaseCatalytic reactions are also important in biotransformation.For example:
Biotransformation
Biotransformation
Biotransformation
Binding reaction
Biotransformation
Biotransformation process II is catalyzed by various specific transferases, which can be expressed as follows:
The receptor in the formula is a foreign body,donorAlso called conjugate, it is a combination of intracellular substances involved in the binding reaction.Mainly variousnucleotideDerivatives, such asUridine diphosphateGlucuronic acid（UDPGA，provideGlucuronic acidGroup, GA), 3 '- phosphoric acid adenylate sulfuric acid (PAPS, providing sulfuric acid group, S=SO3H), adenosylmethionine (SAM,Methyl donor,M=methyl),Acetyl CoA（CH3CO—SCoA，AcetylDonor, CH3-CO diacetyl).In addition, some amino acids (such as glycineglutamine）And its derivatives (such as glutathione) are also important conjugates.Donors or conjugates are normal products of cell metabolism.
