Biosynthesis and Metabolism

Anandamide and 2-AG are produced by neurons when the need arises, act near their site of biosynthesis, and are rapidly metabolized so that their bioactivities are terminated. These characteristics distinguish endocannabinoids from classical or peptide neurotransmitters and suggest that endocannabinoids play a role as activity-dependent, short-range modulators of synaptic function. Such a role is supported by data obtained from electrophysiological and neurochemical experiments. 

The biosynthesis of noladin ether remains unresolved (Fezza et al., 2002). No other 2-0-alkylglycerols have yet been discovered in higher animals. 

Anandamide binds and activates the CBj receptor in vitro. However, in vivo it displays only weak and transient caimabinoid properties. Anandamide s short half-life in vivo, ty 5 min (Willoughby et al, 1997), which hinders the 

FAAH cDNA has been cloned from rat liver (Cravatt et al., 1996), from human and mouse liver (Giang and Cravatt, 1997), and from porcine brain (Goparaju et al, 1999). These four enzymes are composed of 579 amino acids, and their molecular masses are about 63 kDa. The porcine enzyme shows 85, 81 and 80% identity of the deduced amino acid sequence to those of the human, rat and mouse enzymes, respectively (Goparaju et al, 1999). 

Extracellular anandamide, after it serves its function, is rapidly taken up by neuronal and non-neuronal cells by a high-affinity carrier-mediated transport mechanism. This mechanism meets key criteria of carrier-mediated transport, such as fast rate (t, of approximately 4 min), temperature dependence, satura-bility, and substrate selectivity (Beltramo et ah, 1997 Hillard et al., 1997). Furthermore, the transportation of anandamide is independent of sodium ions and is not affected by metabolic inhibitors. The second endogenous camiabinoid, 2-AG, competes for uptake with anandamide. It has been variously reported to exhibit a 2-fold higher affinity for the anandamide transporter than anandamide (Jarrahian et al, 2000), or equal affinity (Piomelli et al, 1999). The molecular structure of this hypothetical anandamide transporter remains unknown. However, it is selective for fatty acid amides or esters, and it is not a fatty acid transporter (Piomelli et al, 1999 Jarrahian et al, 2000). Very recent results indicate that anandamide uptake is a process driven by metabolism and other downstream events, rather than by a specific membrane-associated anandamide carrier (Glaser et al, 2003). 

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Up to this point all our attention has been directed toward aldoses carbohydrates hav ing an aldehyde function in their open chain form Aldoses are more common than ketoses and their role m biological processes has been more thoroughly studied Nev ertheless a large number of ketoses are known and several of them are pivotal inter mediates m carbohydrate biosynthesis and metabolism Examples of some ketoses include d nbulose l xylulose and d fructose... 

Classification of the anabolic steroids is based on chemical stmctures and associated actions. A review of the biosynthesis and metabolism of the naturally occurring estrogens and androgens is available (1). Names, descriptions, approval dates, and recommended doses of the commercial products are found in References 1, 8, and 9. Although steroids may be orally active, the FDA approved mode of adrninistration is the subcutaneous implant. Effective dose is lower with implant rather than oral adrninistration. 

A. Cro2ier andj. R. Hillman, eds.. The Biosynthesis and Metabolism of Plant Hormones, Oxford University Press, Oxford, U.K., 1984. 

There are very few examples of naturally occurring pyrazoles. As indicated in the introduction to this chapter, compounds containing the N—N bond are rare in higher plants and the biosynthesis and metabolism of N—N bonds is still unknown. Withasomnine, 4-phenyl-1,5-trimethylenepyrazole (754), was isolated from the roots of Indian medicinal plants, Withania somnifera Dun, and its structure established by physical methods and total synthesis (68TL5707, 82H( 19)1223). 

Hartmann T, Ober D (2000) Biosynthesis and Metabolism of Pyrrolizidine Alkaloids in Plants and Specialized Insect Herbivores. 209. 207-243 Haseley SR, Kamerling JP, Vliegenthart JFG (2002) Unravelling Carbohydrate Interactions with Biosensors Using Surface Plasmon Resonance (SPR) Detection. 218 93-114... 

The biosynthesis and metabolism of plant hormones. Edited by A. Crozier and J.R. Hillman... 

Russell DW Cholesterol biosynthesis and metabolism. Cardiovascular Drugs Therap 1992 6 103. 

Phytoestrogens may also modulate the concentration of endogenous steroid hormones by binding to and inactivating the enzymes involved in their biosynthesis and metabolism. 

Ignarro, L.J. (1990). Biosynthesis and metabolism of endothelium-derived relaxation factor. Ann. Rev. Pharmacol. Toxicol. 30, 535-560. 

Carotenoids, Vol. 3 Biosynthesis and Metabolism. Birkhauser, Basel, Switzerland, p. 14, 25. 

Walberg, I. and A.-M. Eklund (1998). Degraded carotenoids. Carotenoids, Volume 3 Biosynthesis and Metabolism. G. Britton, S. Liaaen-Jensen and H. Pfander, eds. Basel, Switzerland Birkhauser Verlag, pp. 195-216. 

Destefano-Beltran, L., D. Knauber et al. (2006). Effects of postharvest storage and dormancy status on ABA content, metabolism, and expression of genes involved in ABA biosynthesis and metabolism in potato tuber tissues. Plant Mol. Biol. 61(4-5) 687-697. 

Isselbacher, K. J., cited by Kalckar, H. M., and Maxwell, G. S., Biosynthesis and metabolic function of uridine diphosphoglucose in mammalian organisms and its relevance to certain inborn errors. Physiol. Revs. 38, 88 (1958). 

The biosynthesis and metabolism of nicotinic acid in disease has received little attention metabolic studies deal mainly with normal animals and man (01, R5). After a tryptophan load dose, the main catabolites in the urine are nicotinuric acid, N1-methylnicotinamide, nicotinamide, quinolinic acid, kynurenine, 6-pyridone, anthranilic acid, and 3-hydroxyanthranilic acid. These excretory products were estimated... 

Wood SG, Gottheb D (1978) Evidence from mycelial studies for differences in the sterol biosynthetic pathway of Rhizoctonia solani and Phytophthora cinnamomi. Biochem J 170 343 Nes WD et al (1986) A comparison of cycloartenol and lanosterol biosynthesis and metabolism by the Oomycetes. Expeiientia 42 556... 

Coenzyme A is used as the alcohol part of thioesters, which are more reactive than oxygen esters (see Section 7.9.3) and are thus exploited in biochemistry in a wide range of reactions, e.g. fatty acid biosynthesis and metabolism (see Section 15.5). 

This is a complex molecule, made up of an adenine nucleotide (ADP-3 -phosphate), pantothenic acid (vitamin B5), and cysteamine (2-mercaptoethylamine), but for mechanism purposes can be thought of as a simple thiol, HSCoA. Pre-eminent amongst the biochemical thioesters is the thioester of acetic acid, acetyl-coenzyme A (acetyl-CoA). This compound plays a key role in the biosynthesis and metabolism of fatty acids (see Sections 15.4 and 15.5), as well as being a building block for the biosynthesis of a wide range of natural products, such as phenols and macrolide antibiotics (see Box 10.4). 

Nelson SD, McClanahan RH, Knebel N, Xhomassen D, Gordon WP, Doshi S, Xhe metabolism of (A)-(+)-pulegone, a toxic monoterpene, in Petrosky RJ, McCormick SP (eds.), Secondary-Metabolite Biosynthesis and Metabolism, Plenum Press, New York, USA, 1992. 

Napoli, J. (1996). Retinoic acid biosynthesis and metabolism. FASEB ]. 10, 993-1001. 

NT562 Leete, E. Biosynthesis and metabolism NT572 of the tobacco alkaloids. Alkaloids ... 

Biosynthesis and Metabolism.—Pathways and Reactions. Two reviews of carotenoid biosynthesis discuss, respectively, the early steps and the later reactions." The former paper deals with the mechanism of formation of phytoene and the series of desaturation reactions by which phytoene is converted into lycopene, and also describes in detail the biosynthesis of bacterial C30 carotenoids. The second paper" presents details of the mechanism and stereochemistry of cyclization and the other reactions that involve the carotenoid C-1 —C-2 double bond and the later modifications, especially the introduction of oxygen functions. 

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