CHAPTER 41: Pantetheine and Pantetheinase: From Energy Metabolism to Immunity

Pantetheine is an intermediate metabolite of coenzyme A, prerequisite for metabolic reactions. Pantetheinase is an enzyme hydrolysing pantetheine into pantothenic acid (vitamin B5) and cysteamine. The pantothenic acid generated is usually recycled for another biosynthesis of coenzyme A, indicating the step of hydrolysis of pantetheine by pantetheinase is important for the “salvage pathway” of the coenzyme A biosynthesis. The pantetheinase gene family consists of three genes, pantetheinase/vanin-1, GPI-80/vanin-2, and vanin-3. Recent studies using genetically modified mice suggest that the major role of pantetheinase/vanin-1 is to regulate inflammatory reactions by producing cysteamine. Cysteamine has been used for the treatment of cystinosis. In addition, cysteamine has antioxidative activity, which enables peripheral organ to be resistant to oxidative stress. On the other hand, GPI-80/vanin-2 has been reported to regulate adherence via Mac-1 (CD11b/CD18) in human neutrophils and cellular locomotion. GPI-80/vanin-2 is released from activated neutrophils. Expression of human vanin-1 and vanin-3 are induced in inflammatory skin. Therefore, pantetheinase gene family may be involved in inflammatory process. Pantetheinase gene family would be a new and good target for anti-inflammatory drugs.