Degradation by deamination

When a Mannich reaction is carried out between a substrate containing at least two active hydrogen atoms and a primary or a bis-secondary amine, a polycondensation takes place with production of a polymeric derivative. Fhe polycondensation can also occur when both an NH group and one active hydrogen atom arc present in the same molecule. The reaction product is thus characterized by the presence of the methylene moiety, whieh is derived from the formaldehyde, and forms the polymer backbone, with the consequent possibility of polymer degradation by deamination or dcaminomethy-lation both of these reactions are typical of Mannich bases (Chap. II, A). 

An interesting study examined the anodic oxidation of EDTA at alkaline pH on a smooth platinum electrode (Pakalapati et al. 1996). Degradation was initiated by removal of the acetate side chains as formaldehyde, followed by deamination of the ethylenediamine that formed glyoxal and oxalate. Oxalate and formaldehyde are oxidized to CO2, and adsoption was an integral part of the oxidation. 

In analogy with phenol, aniline is carboxylated to 4-aminobenzoate followed by reductive deamination to benzoate (Schnell and Schink 1991), which is degraded by pathways that have already been elaborated. 

The aerobic degradation of L-cysteate by Paracoccus pantotrophus is carried out by deamination to 3-sulfolactate from which sulfite is lost with the formation of pyruvate (Cook et al. 2006). The activity of the lyase (3-L-sulfolactatesulfolyase) has been shown to involve pyridoxal 5 -phosphate, and the enzyme has been found in a number of organisms using L-cysteate either as a source of carbon or as an electron acceptor (Denger et al. 2006). 

Purine (left). The purine nucleotide guano-sine monophosphate (CMP, 1) is degraded in two steps—first to the guanosine and then to guanine (Gua). Guanine is converted by deamination into another purine base, xanthine. 

The first generation of antidepressants, MAO (monoamine oxidase) inhibitors, inhibited neurotransmitter degradation by inhibiting monoamine deoxidase, a flavin containing enzyme, found in the mitochondria of neurons and other cell types, that oxidatively deaminates naturally occurring sympathomimetic monoamines, such as norepinephrine, dopamine, and serotonin within the presynapse. In 1952, isoniazid and its isopropyl derivative, iproniazid (1), were developed for the treatment of tuberculosis, where it was subsequently found that these agents had a mood enhancing effect on... 

Purine nucleotides are degraded by a pathway in which they lose their phosphate through the action of 5 -nucleotidase (Fig. 22-45). Adenylate yields adenosine, which is deaminated to inosine by adenosine deaminase, and inosine is hydrolyzed to hypoxanthine (its purine base) and D-ribose. Hypoxanthine is oxidized successively to xanthine and then uric acid by xanthine oxidase, a flavoenzyme with an atom of molybdenum and four iron-sulfur centers in its prosthetic group. Molecular oxygen is the electron acceptor in this complex reaction. 

Most hormones have a half-life in the blood of only a few minutes because they are cleared or metabolized very rapidly. The rapid degradation of hormones allows target cells to respond transiently. Polypeptide hormones are removed from the circulation by serum and cell surface proteases, by endocytosis followed by lysosomal degradation, and by glomerular filtration in the kidney. Steroid hormones are taken up by the liver and metabolized to inactive forms, which are excreted into the bile duct or back into the blood for removal by the kidneys. Catecholamines are metaboli-cally inactivated by O-methylation, by deamination, and by conjugation with sulfate or glucuronic acid. 

Distribution and elimination Adencsine is rapidly taken up by roost types of cells and rapidly degraded ty deamination or phosphorylation. 

---