Biomaterial Database

Regulation of fatty acid biosynthesis by intermediates of the cholesterol biosynthetic pathway. 1996

E C Ku

Research Department, CIBA Corporation, Summit, New Jersey 07901, USA.

The biosynthesis of cholesterol and fatty acid (FA) proceeds by independent pathways. Information is lacking on potential interaction that could provide feedback regulation between these pathways. In an attempt to search for a new approach to produce a dual effect on regulation of these two processes, we have identified mevalonate-5-diphosphate (MevPP) decarboxylase, an enzyme of the cholesterol biosynthesis pathway, the inhibition of which leads not only to the suppression of cholesterol but also FA biosynthesis. Mechanistic studies with Hep G2 cells using specific inhibitors for MevPP decarboxylase and related enzymes reveal that the inhibitory effect on FA biosynthesis is mainly due to the accumulation of MevPP, resulting from MevPP decarboxylase inhibition. The present study proposes a new mechanism through which interpathway regulation could take place between the cholesterol and FA cascades.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008113	Liver Neoplasms	Tumors or cancer of the LIVER.	Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008148	Lovastatin	A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.	Lovastatin, 1 alpha-Isomer,Mevinolin,6-Methylcompactin,Lovastatin, (1 alpha(S*))-Isomer,MK-803,Mevacor,Monacolin K,1 alpha-Isomer Lovastatin,6 Methylcompactin,Lovastatin, 1 alpha Isomer,MK 803,MK803,alpha-Isomer Lovastatin, 1
D008798	Mevalonic Acid	A dihydroxy monocarboxylic acid and precursor in the biosynthetic pathway known as the mevalonate pathway, which produces terpenes and steroids that are vital for diverse cellular functions.	Mevalonate,Acid, Mevalonic
D002262	Carboxy-Lyases	Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1.	Carboxy-Lyase,Decarboxylase,Decarboxylases,Carboxy Lyase,Carboxy Lyases
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D006528	Carcinoma, Hepatocellular	A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.	Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006706	Homeostasis	The processes whereby the internal environment of an organism tends to remain balanced and stable.	Autoregulation
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man