Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Liver
The Role of the Liver in Protein Metabolism
Detoxification of Various Substances in the Liver

Foreign substances (xenobiotics) in the Liver are frequently converted into less toxic or even indifferent compounds. Arguably, it is only in this sense that we can speak of their "detoxification" by the liver. This is achieved through oxidation, reduction, methylation, Acetylation, and conjugation with various molecules. It should be noted that oxidation, reduction, and Hydrolysis of foreign compounds in the liver are carried out primarily by microsomal Enzymes. Alongside the microsomal pathway, peroxisomal oxidation also takes place in the liver. Peroxisomes are Microbodies found in hepatocytes; they can be regarded as specialized oxidative Organelles. These microbodies contain urate oxidase, lactate oxidase, D-Amino Acid Oxidase, and catalase. The latter catalyzes The breakdown of hydrogen peroxide generated by the aforementioned oxidases—hence the name peroxisomes. Like microsomal oxidation, peroxisomal oxidation is not coupled with The formation of high-energy phosphate bonds.

The liver also features a wide range of "protective" syntheses, such as urea synthesis, which neutralizes highly toxic ammonia. As a result of putrefactive processes in the intestine, phenol and cresol are formed from Tyrosine, while skatole and indole are produced from Tryptophan. These substances are absorbed and transported via the bloodstream to the liver, where they are detoxified by forming paired conjugates with sulfuric or glucuronic acid.

The detoxification of phenol, cresol, skatole, and indole in the liver occurs through the interaction of these compounds not with free sulfuric and glucuronic acids, but with their so-called active forms: PAPS and UDPGA*.

Glucuronic acid is involved not only in neutralizing the decay products of protein substances originating in the gut, but also in binding a range of other toxic compounds generated during tissue METABOLISM. Specifically, free (indirect) bilirubin, which exhibits significant toxicity, reacts with glucuronic acid in the liver to form bilirubin mono- and diglucuronides. Hippuric acid, synthesized in the liver from benzoic acid and Glycine, is another normal metabolite.

In humans, hippuric acid synthesis occurs predominantly in the liver. Therefore, clinical practice frequently employs the Quick-Pytel test (assuming normal renal function) to assess the liver's antitoxic capacity: following a sodium benzoate load, The amount of synthesized hippuric acid is measured in the urine. In parenchymal liver lesions, hippuric acid synthesis is diminished.

Methylation processes are widespread in the liver. For instance, prior to urinary excretion, nicotinamide (Vitamin PP) is methylated in the liver to yield N-methylnicotinamide. Alongside methylation, acetylation processes proceed intensively as well**. Specifically, various sulfonamide drugs undergo acetylation in the liver.

An example of hepatic detoxification of toxic products via reduction is The conversion of nitrobenzene to p-aminophenol. Many aromatic Hydrocarbons are detoxified through oxidation, yielding the corresponding carboxylic acids.

The liver plays an active role in the inactivation of various Hormones. Carried by the bloodstream to the liver, hormones generally experience a sharp decline or complete loss of activity. For example, Steroid Hormones undergo microsomal oxidation and are thus inactivated, subsequently transforming into the respective glucuronides and sulfates. Catecholamines undergo oxidation in the liver under The Influence of amine oxidases, and so forth.

* Before reacting with PAPS or UDPGA, indole and skatole are oxidized into hydroxyl-bearing compounds (indoxyl and skatoxyl). Consequently, the resulting paired conjugates are skatoxyl sulfuric acid or skatoxyl glucuronic acid, respectively.

** The content of the acetylation coenzyme (HS-CoA) in the liver is 20 times higher than its concentration in Muscle tissue.

These Examples clearly demonstrate that the liver is capable of inactivating a wide range of potent physiological and foreign (including toxic) substances.