Lipid metabolism modulation

Vitamin B6-coenzyme is involved in a variety of reactions, e.g., in the immune system, gluconeogenesis, erythrocyte fimction, niacin formation, nervous system, lipid metabolism, and in hormone modulation/gene expression [1, 2]. 

A wide variety of other biochemical effects has been reported to be associated with treatment of cells with vinblastine, vincristine, and related compounds (S). These effects include inhibition of the biosynthesis of proteins and nucleic acids and of aspects of lipid metabolism it is not clear whether such effects contribute to the therapeutic or toxic actions of vincristine and vinblastine. Vinblastine and vincristine inhibit protein kinase C, an enzyme system that modulates cell growth and differentiation (9). The pharmacological significance of such inhibition has not been established, however, and it must be emphasized that the concentrations of the drugs required to inhibit protein kinase C are several orders of magnitude higher than those required to alter tubulin polymerization phenomena (10). 

Kok, N.N., Taper, H.S., and Delzenne, N.M., Oligofructose modulates lipid metabolism alterations induced by a fat-rich diet in rats, J. Appl. Toxicol., 18, 47-53, 1998. 

FABPs have been implicated in transmembrane and intracellular transport of fatty acids (Veerkamp et al., 1991 Storch and Thumser, 2000). These are a group of tissue-specific proteins of about 14-15 kDa that bind long-chain fatty acids (C16-C20) with high affinity and a molar stoichiometry of 1 1. Most bind unsaturated fatty acids with higher affinity than saturated fatty acids. In addition to transport functions it has been proposed that they modulate specific enzymes of lipid metabolism, regulate expression of fatty acid-responsive genes, maintain cellular membrane fatty acid levels, and reduce the concentration of fatty acids in the cell, thereby removing their inhibitory effect on metabolic processes. 

Carta, G., Angioni, E., Murru, E., Melis, M. P., Spada, S., and Banni, S. 2002. Modulation of lipid metabolism and vitamin A by conjugated linoleic acid. Prostaglandins, Leukot. Essent. Fatty Acids, 67,187-191. 

Norata GD, Ongari M, Uboldi P, Pellegatta F, Catapano AL (2005) Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells. Int J Mol Med 16 717-722... 

R.B. Cornell and R.S. Arnold. Modulation of the activities of enzymes of membrane lipid metabolism by non-bi-layer-forming lipids. Chem. Phys. Lipids, 1996, 83, 215-227. 

Despite its proven benefit in the control of blood glucose, PPARy agonists have been associated with an increased incidence of myocardial infarction and death from cardiovascular causes [71]. Numerous companies are therefore working actively on specific PPARa modulators, and a number of discovery and preclinical programs have been initiated with the aim of improving potency and selectivity compared to the fibrates. PPARa-selective compounds that are currently under development are shown in Figure 13.9. With the exception of K-lll (for a recent review, see Ref. [72]), which is developed for the treatment of type 2 diabetes mellitus, the development of all known PPARa activators is focused on lipid metabolism. 

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