Neurotransmitters biosynthesis

Fatty acid biosynthesis Cholesterol biosynthesis Neurotransmitter biosynthesis Nucleotide biosynthesis Detoxification... 

While the majority of aromatic hydroxylases are bacterial catabolic enzymes, several have been discovered in mammals, playing a role in ubiquinone biosynthesis, neurotransmitter chemistry, and cell differentiation. ... 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Psychoactive drugs can influence neurotransmission at its five different stages (Chapter 2). First, they may modify the biosynthesis of a neurotransmitter. Second, they can increase or decrease their storage within the presynaptic neuron. Third, they may stimulate or inhibit neurotransmitter release from the synaptic bouton. Fourth, they may affect the binding of the neurotransmitters to its receptor. Finally, they can retard the neurotransmitter s inactivation. Some examples of each of these stages will be given below, but it should be noted that many drugs affect several of these processes. 

Biosynthesis See also Anabolism Biosynthesis is also used to describe the conversion of inactive (precursor) molecules into physiologically active ones as in the biosynthesis of a neurotransmitter. 

Cyclic AMP Stimulation or inhibition of the biosynthesis of the second messenger cyclic adenosine-S jS -monophosphate occurs through the activation of Gs or G protein-coupled neurotransmitter receptors, respectively. 

The role of the nervous system in pheromone biosynthesis in moths is not clearly understood. Christensen and co-workers [208-211] proposed that the neurotransmitter octopamine may be involved as an intermediate messenger during the stimulation of sex pheromone production in H. virescens. These workers suggested that octopamine was involved in the regulation of pheromone production and that PBAN s role lies in the stimulation of octopamine release at nerve endings. However, contradicting results concerning octopa-mine-stimulated pheromone production were reported in the same species as well as other moth species [163,172,212-214]. 

The biosynthesis of neuropeptides is fundamentally different from that of conventional neurotransmitters 321 Many of the enzymes involved in peptide biogenesis have been identified 321... 

Probably the most striking difference between neuropeptides and conventional neurotransmitters is in their biosynthesis (Fig. 18-2). Neuropeptides are derived from larger, inactive precursors that are generally at least 90 amino acid residues in length [2-4]. The simplest example is prolactin, a pituitary product. The signal sequence for... 

The biosynthesis of neuropeptides is fundamentally different from that of conventional neurotransmitters. 

TABLE 23-3 Examples of proteins regulated by phosphorylation Enzymes involved in neurotransmitter biosynthesis Tyrosine hydroxylase Tryptophan hydroxylase Neurotransmitter receptors Adrenergic receptors Dopamine receptors Opioid receptors Glutamate receptors Many others... 

The regulation of phosphorylation of tyrosine hydroxylase is affected by stimuli that increase Ca2+ or cAMP concentrations in neurons, including nerve impulse conduction and certain neurotransmitters in well-defined regions of the nervous system, in the adrenal medulla and in cultured pheochromocytoma cells. In addition, tyrosine hydroxylase phosphorylation is stimulated by nerve growth factor in certain cell types, possibly via the activation of ERKs. These changes in the phosphorylation of tyrosine hydroxylase have been shown to correlate with changes in the catalytic activity of the enzyme and in the rate of catecholamine biosynthesis. 

Energy production amino acid and neurotransmitter biosynthesis... 

Normal biochemical events surrounding the maintenance and functions of the nervous system centers around energy metabolism, biosynthesis of macromolecules, and neurotransmitter synthesis, storage, release, uptake, and degradation. Measurement of these events is complicated by the sequenced nature of the components of the nervous system and the transient and labile nature of the moieties involved. Use of measurements of alterations in these functions as indicators of neurotoxicity is further complicated by our lack of a complete understanding of the normal operation of these systems and by the multitude of day-to-day occurrences (such as diurnal cycle, diet, temperature, age, sex, and endocrine status) which are constantly modulating the baseline system. For detailed discussions of these difficulties, the reader is advised to see Damstra and Bondy (1980, 1982). 

Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, j., and Mendel, R. R. The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells, Proc Natl Acad Sci USA 1999, 96, 1333-1338. 

Neurotransmitter biosynthesis pathways possible involvement of CYP2D6 ... 

Genes encoding for the biosynthesis and catabolism of neurotransmitters Tryptophan hydroxylase (TPH)... 

D. E. Duggan, S.D. Aster, Selective inhibitors of biosynthesis of aminergic neurotransmitters, Nature 274 (1978) 906-908. 

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