Acid hydrolases biosynthesis

Fig. 2. Simplified schema for the integration of acid hydrolase biosynthesis and ixissible sites of control Acid hydrolase biogenesis would be determined and controlled genetically via mRNA coding. Full biological expression requires ribosome-imlysome formation, membrane attachment ( stereoorientation) and formation of the enzyme-synthesizing unit...

Lysosomal Acid Hydrolase Biosynthesis Induciton of Stimulation... 

Studies on the biosynthesis of lactones have shown that epoxidation of unsaturated fatty acids like, e.g., linoleic and linolenic acid may represent a common pathway to oxygenated derivatives of fatty acids. Epoxy fatty acid hydrolases were identified as key enzymes that exhibit high regioselectivity and enantiose-lectivity [25, 26]. 

In vitamin E-deficient rabbits, the activity of creatine phosphokinase increases, apparently in muscle first and in blood later. The administration of a-tocopherol normalizes the serum CPK levels. Because ethi-onine mimicks this effect of vitamin E, it has been proposed that vitamin E acts as a repressor of the gene responsible for the biosynthesis of creatine phosphokinase. It was also proposed that a similar mechanism could explain the increase in acid hydrolases observed in muscles of vitamin E-deficient animals. In the latter case, such an interpretation is unlikely because the appearance of the hydrolase is associated with the appearance of macrophages. 

Scheme 10.30 Part of clavulanic acid biosynthesis. Bonds installed byclavaminic acid synthase (CAS) are circled. CAS clavaminic acid synthase. PAH proclavaminic acid amidino hydrolase.

Specific chain length fatty acids could be produced in two ways. One is through the action of a thioester hydrolase that interacts with fatty acid synthetase to produce fatty acids shorter in length. Aphids produce myristic acid (14 carbons) and a specific thioester hydrolase releases the fatty acid from fatty acid synthetase after 6 additions of malonyl-CoA. If the hydrolase is not present then the fatty acid synthetase produces stearic acid [27]. A specific thioester hydrolase was ruled out in the biosynthesis of moth sex pheromones because labeling studies showed that longer chain length fatty acids were incorporated into shorter chain length pheromone components [22,28]. 

Biosynthesis of flavonoids starts with the conversion of phenylalanine or tyrosine to cinnamic acid by phenylalanine ammonia lyase (PAL) (Hahlbrock and Grisebach, 1975). Subsequent reactions are catalyzed by cinnamic acid 4-hydrolase to form 4-hydroxyl cinnamic acid (p-coumaric acid). The p-coumaric acid is then catalyzed by p-coumarate CoA ligase to form p-coumaroyl CoA. 

Extensive studies on the endocannabinoid system have revealed a number of cannabinergic proteins involved in the inactivation and biosynthesis of endocannabinoids. These include fatty acid amide hydrolase (FAAH) (Di Marzo et al. 1994 Gaetani et al. 2003 Piomelli et al. 1999), monoglyceride lipase (MAG) (Dinh et al. 2002), and the anandamide transporter (ANT) (Beltramo et al. 1997 Di Marzo et al. 1994 Fegley et al. 2004 Hillard et al. 1997). The above three proteins and the two cannabinoid receptors have received considerable attention and show great promise as potential targets for the development of novel medications for various conditions, including pain, immunosuppression, peripheral vascular disease, appetite enhancement or suppression, and motor disorders. 

---