N-glycosidases and ribotoxins: its methagenetic action. Dissemination 75th
Cell death is a priority source to cease operation of ribosomes either from the internal causes own genetic code or due to external causes from ribosomal inactivating substances function. 4 groups of ribosome inactivating substances are currently known:
1. Ribosome inactivating proteins (RIPs hereinafter) are N-glycosidases which act on the genomic DNA, messenger RNA and ribosomal RNA, through the elimination of Adenine and consequently the interruption of the specific protein synthesis both in eukaryotic cells as prokaryotic. This locates the emergence of these substances on a timescale, very primitive though not initial, in the evolution of life.
To date, two types of RIPs are known, all vegetable: From "type 1" (saponin S6) formed by a polypeptide chain (mw 27-32 kDa) glycosidase activity and "Type 2" (abrin, Ebulin , modeccin, nigrin, Racemosin, ricin, viscumin, volkesin) consisting of two polypeptide chains (pm56-65 KDa), a so-called A (glycosidase activity) and one named B (lectin properties).
(2) A second group of RIPs of fungal origin (hereinafter ribotoxins protein) consists of c-sarcin and clavina (type I), alpha-sarcin and Giantish (type II), mitogillin and Asp f1 (type III). Protein structure all have comprised between 75 and 150 amino acids and are synthesized by Aspergillus and Penicillium.
(3) Two other substances, heretofore have not been classified either as RIPs or as protein ribotoxins, even taking protein structure, which act similarly. There are two bacterins toxins produced by Corynebacterium diphtheriae (diphtheria toxin) and Pseudomonas aeruginosa (exotoxin A).
(4) Finally three other inhibitory substances of protein synthesis in the ribosomes are known, that have no protein structure therefore can not be considered ribotoxins protein, and which are synthesized by actinomycetes of the genus Streptomyces: cicloheximidina, pactamicina and puromycin.
Ribosomes are organelles target action RIPs, protein ribotoxins, non-protein ribotoxins and inhibitors produced by actinomycetes. Consequently inactivation of them and slowing down or stopping production of specific proteins and thus deficient activity or cell death is produced.
The general opinion is that some of these substances are developed in a very early time, between the start of the pre existence of the occurrence of prokaryotes and eukaryotes, when there no exist an immune system unless melanin production and deposition of calcium in unicellular beings. In later evolutionary epochs there have been other ribosomal inhibitors as evidenced by the existence of two distinct types according to target cells: a group affects prokaryotic and eukaryotic cells, while another group affects only eukaryotic cells.
Natural biosynthesis of RIPs chain and protein ribotoxins, due to its protein structure, implies the existence of an active genetic code. Therefore it is likely that the first RIPs were developed by primitive prokaryotes (this would imply that the genetic code was in the original circular DNA chain and this mechanism could be used in the self-destruction of cancer cells), to control the population of its competitors also prokaryotes, and then the new species evolved from prokaryotes, genetically RIPs positive, used to control the virus, bacteria, fungi and insects predators.
Has also been achieved RIPs heterologous production and ribotoxins transferring protein, involved the piece of genetic code, of prokaryotic species to be easily grown in fermenters. Cytotoxic proteins thus obtained, maintained glycosylation capabilities, folding and formation of disulfide bridge identical to the production of homologous (of the original species).
Studies and application of N-glycosidases has always been hampered by the high acute toxicity of the first RIPs known (abrin, modeccin, ricin, viscumin and volkensin) but recently have found less toxic RIPs (ebilin, nigrin and Racemosin) whose management will allow the study of the mechanism of methagenetic action and can also be used as a group control efficacy studies of pronutrients as stimulants of the ribosomal function.