Regulation of Fatty Acid Biosynthesis by Intermediates of the Cholesterol Biosynthetic Pathway

• Published in: Biochemical and biophysical research communications Vol. 225; no. 1; pp. 173 - 179
• Main Author: Ku, Edmond C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05-08-1996
• Subjects: ACIDE GRAS; ACIDE ORGANIQUE; ACIDOS GRASOS; ACIDOS ORGANICOS; ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Anticholesteremic Agents - pharmacology; Carboxy-Lyases - antagonists & inhibitors; Carcinoma, Hepatocellular; CHOLESTEROL; Cholesterol - biosynthesis; COLESTEROL; CULTIVO DE CELULAS; CULTURE DE CELLULE; Fatty Acids - biosynthesis; GENERO HUMANO; GENRE HUMAIN; Homeostasis; Humans; INHIBICION; INHIBIDORES DE ENZIMAS; INHIBITEUR D'ENZYME; INHIBITION; Kinetics; LIASAS; Liver Neoplasms; Lovastatin - pharmacology; LYASE; METABOLISME; METABOLISME DES LIPIDES; METABOLISMO; METABOLISMO DE LIPIDOS; Mevalonic Acid - analogs & derivatives; Mevalonic Acid - pharmacology; Structure-Activity Relationship; TRANSFERASAS; TRANSFERASE; Tumor Cells, Cultured; VIA BIOQUIMICA DEL METABOLISMO; VOIE BIOCHIMIQUE DU METABOLISME
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.1149

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.