What Is Biotransformation?

Biotransformation ^[1] refers to a metabolic process in which the chemical structure of a toxicant changes after being catalyzed by an enzyme, that is, the toxicant has undergone a qualitative change. Biotransformation is an important event that occurs before the toxicant is eliminated in the body, and its typical outcome is the production of non-toxic or low-toxic metabolites. Therefore, biological transformation and detoxification have been equated. However, in many cases, toxic metabolites produced by biotransformation can cause tissue damage. The biological transformation at this time is called biological activation. Also called poisoning.

Biological transformation is also called "metabolic transformation". The chemical change process of foreign compounds in the body under the action of enzyme catalysis or non-enzyme. Biotransformation can reduce the toxicity of foreign compounds and detoxify them. It can also increase the toxicity of some foreign compounds (biological activation), which is generally called the duality of biotransformation. For example, soil microorganisms can convert lindane to carbon dioxide, while underwater microorganisms can convert inorganic mercury into methylmercury, which is more toxic. Biotransformation of organic substances The energy and substances necessary to maintain biological life activities. Artificial inert organic substances are generally more difficult to be transformed by organisms and pollute the environment. The process of absorption, distribution and excretion of chemical poisons in the body is called biological transport ^[1]

Mechanism of Enzymes Enzymatic reactions are vital to organisms. In the mild environment of living organisms, most biological organic molecules are stable, and the speed of non-catalytic reactions is usually slow. Without the catalysis of enzymes, many chemical reactions and biological functions in the cell would not be possible. Enzymes, as biocatalysts, are most prominently characterized by high efficiency in promoting reaction speed and specificity in substrates. The efficiency and specificity of enzymes are two aspects of the same thing, the two are unified ^[2]

The biotransformation reaction in the liver can be mainly divided into a first phase reaction (oxidation reaction, reduction reaction, hydrolysis reaction) and a second phase reaction (conjugation reaction).

Factors affecting biotransformation are as follows:

biological

The binding reactions in biotransformation can be divided into the following types due to the different types of conjugates. Examples of various types of binding reactions are as follows:

Biotransformation is generally divided into two consecutive action processes and . In process , foreign substances change their chemical structure through oxidation, reduction or hydrolysis reaction under the catalysis of the relevant enzyme system to form certain active groups (such as -OH , SH, COOH, NH2, etc.) or further expose these reactive groups. In process II, the primary metabolite of the foreign body is catalyzed by other enzyme systems to combine with certain compounds in the cell through the above-mentioned active groups to form a binding product (secondary metabolite). The polarity (hydrophilicity) of the binding product is generally enhanced to facilitate excretion. For example, the biotransformation process of carbamate insecticide fenapyr (cewayine) is as follows:

Biotransformation

Foreign body biotransformation generally has to go through these two continuous processes, but there are also some foreign bodies that, because they already contain the corresponding active groups, do not need to go through Process I to directly combine with the substances in the cell to complete their biotransformation.

Biotransformation oxidation reaction

The oxidation reaction in the process of foreign body biotransformation is carried out under the catalysis of a mixed function oxidase system (also known as a monooxygenase system, a hydroxylase system or a cytochrome P-450 enzyme system). The oxidation of foreign matter can be expressed by the following formula:

Biotransformation

NADPH2: reduced coenzyme II; NADP: oxidized coenzyme II This enzyme system is very active, but its specificity is poor. Almost all foreign substances with certain fat solubility can be oxidized under its catalysis, so it is often called Mixed functional oxidase. It is believed that the oxidation reactions it can catalyze are shown in the table.

Biotransformation reduction reaction

Most of the reduction reactions in the biological transformation process I are carried out under the catalysis of various reductases (such as alcohol dehydrogenase, aldehyde dehydrogenase, nitroreductase, azoreductase, etc.). For example, reductive dehalogenation (such as the reduction of DDT to DDD) is an important way for foreign substances to undergo biological transformation through reduction reactions. As to whether the cytochrome P-450 enzyme system can also catalyze its reverse reaction (reduction reaction), it is still inconclusive.

Biotransformation hydrolysis reaction

The hydrolysis reaction in the biotransformation process I is the conversion of foreign substances such as esters and amides. Organophosphorus pesticides belong to esters or amides chemically, so this type of reaction catalyzed by corresponding hydrolases (such as esterases, amidases, etc.) is also important in biological transformation. E.g:

Biotransformation

Biotransformation

Biotransformation

Biotransformation

Biotransformation binding reaction

The biotransformation process is catalyzed by various specific transferases and can be expressed by the following formula:

Biotransformation

The acceptor in the formula is a foreign body, and the donor is also called a conjugate, which is an intracellular substance conjugate involved in the binding reaction. Mainly various nucleotide derivatives, such as uridine diphosphate glucuronic acid (UDPGA, providing glucuronic acid group, GA), 3-phosphoadenosine sulfate (PAPS, providing sulfuric acid group, S = SO3H ), Adenosylmethionine (SAM, methyl donor, M = methyl), acetyl-CoA (CH3CO-SCoA, acetyl donor, CH3-CO diacetyl). In addition, certain amino acids (such as glycine, glutamine) and their derivatives (such as glutathione) are also important conjugates. Donors or conjugates are normal products of cell metabolism.