Metabolic regulation proteolysis

INSULIN. Some protein hormones are synthesized in the form of inactive precursor molecules, from which the active hormone is derived by proteolysis. For instance, insulin, an important metabolic regulator, is generated by proteolytic excision of a specific peptide from proinsulin (Figure 15.3). 

Brown MS, Goldstein JL. The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997 89 331-340. 

Brown, M.S., and Goldstein, J.L. (1997) The SREBP Pathway Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor, Cell 89, 331-340. 

A calpain inhibitor, the DPK of N-dimethyltyrosine, was isolated from Streptomyces griseus and this compound showed activity in the calpain assay as described by Alvarez etal Calpain is a cytosolic protease regulated by calcium and is distributed in mammalian and avian cells. Calpain catalyzes proteolysis of target protein in cells, causing changes in metabolic processes such as the activation of protein kinase C, neuropeptide metabolism, and the activation of platelets. It is proposed that these inhibitors can be used in the treatment of neurodegen-erative diseases. 

Cellular cholesterol levels are regulated, not only by feedback inhibition of cholesterol synthesis, but also by feed-forward regulation of cholesterol metabolism. Excess cholesterol is metabolized to oxysterols. In addition to blocking SCAP-facilitated proteolysis of SREBP and thereby downregulating endogenous cholesterol synthesis and LDL receptor levels, oxysterols also activate bile acid synthesis (Chapter 15) and cholesterol esterification, which further reduces the cellular content of unesterified cholesterol. 

Insulin, Inutral Optisulin long. Polypeptide hormone produced in the beta cells of the islets of Laager-bans situated in the pancreas of all vertebrates. Synthesized in vivo via a single chain polypeptide precursor, proinsulin, native conformation has been established. Secreted directly into the bloodstream where it regulates carbohydrate metabolism, influences the synthesis of protein and of RNA, and the formation and storage of neutral lipids. The first protein for which chemical structure and precise mol wt were determined Sanger, Tuppy, Biochem. J. 49, 463, 481 (1951) ... 

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