Feedback repression

Figure 24-13 Some biosynthetic reactions of aspartate Q, feedback inhibition and El/ feedback repression.

Attenuation. A major mechanism of feedback repression, known as attenuation, depends not upon a repressor protein but upon control of premature termination. It was first worked out in detail by Yanofsky et al. for the trp operon of E. coli and related bacteria.184 186 Accumulation of tryptophan in the cell represses the trp biosynthetic operon by the action of accumulating tryptophanyl-tRNATlP, which specifically induces termination in the trp operon. Other specific "charged" arnino-acyl-tRNA molecules induce termination at other amino acid synthesis operons. 

Whereas degradative enzymes are usually controlled by induction and catabolite regulation, the biosynthetic enzymes are chiefly controlled by feedback regulation. The two types included in this category are feedback (or end product) inhibition and feedback repression. 

Feedback repression is the inhibition of formation of one or more enzymes in a pathway by a derivative of the end product. In many (but not all) amino acid biosynthetic pathways, the amino add end product must first combine with its transfer RNA (tRNA) before it can cause repression. Feedback repression is a widespread regulatory device especially for the synthesis of molecules intended for incorporation into macromolecules, e.g. amino adds, purines, and pyrimidines. Synthesis of vitamins also appears to be controlled by feedback repression, as well as by catabolite regulation (Birnbaum et al, 1967 Sasaki, 1965 Newell and Tucker, 1966 Wilson and Pardee, 1962 Papiska and Lichstein, 1968). Regulation of vitamin synthesis is important since only a small number (probably about 1000) of vitamin molecules are required per cell whereas many molecules of an average amino acid (probably 50 million) are required. An extremely wasteful case of vitamin overproduction would develop if enzymes for vitamin synthesis were produced at the same rate and were as active as the amino acid biosynthetic enzymes. 

Isoenzymes. In this case, multiple enzymes are made each carries out the same reaction but is regulated by a different end product. This mechanism is used in both feedback inhibition and feedback repression. A well known example of such control is the aspartic acid family in E. coli where the three aspartokinases are regulated by lysine, threonine and methionine respectively (Stadtman, 1968). 

The L-arabinose regulon, besides being specifically regulated through the effect of L-arabinose on the repressor-activator equilibrium, is also subject to self-catabolite repression (feedback repression) caused by... 

Mitchell JL, Judd GG, Bareyal-Leyser A, Ling SY (1994) Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells. Biochem J 299 19-22 Murai N, Shimizu A, Murakami Y, Matsufuji S (2009) SubceUular localization and phosphorylation of antizyme 2. J CeU Biochem 108 1012-1021 Murakami Y, Matsufuji S, Kameji T, Hayashi S, Igarashi K, Tamura T, Tanaka K, Ichihara A (1992) Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature (Lond) 360 597-599... 

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