Signaling systems synthase

The interaction of estrogen receptors with signaling systems of the cell membrane that respond to growth factors and mediate nongenomic, fast actions of estrogens will be reviewed as well. These mechanisms have a growing importance in the comprehension of phenomena like the induction of endothelial NOS (nitric oxide synthase) by estrogens (Rubanyi et al. 2002). 

The genome contains about 1500 genes, 300 of which encode membrane proteins, many with as yet unknown functions [15]. The sequences encoding for membrane proteins comprise genes such as the FiFq ATP synthase complex and various oxido-reductases such as cytochrome o, several transporters and a variety of two-component signaling systems (the equivalent of eukaryotic receptors). Some of the recognized transporters are illustrated in Figure 2. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

The availability of both the cataboHc aldolase and the uniquely synthetic anabolic synthase made it possible to assemble a novel continuous assay for the determination of the metabolite N-acetylneuraminic acid [46]. A combination of both enzymes, in the presence of an excess of PEP, will start a cycle in which the determinant sialic acid will undergo a steady conversion of cleavage and re-syn-thesis as a futile cycle (Scheme 2.2.5.24). With each progression, however, 1 equiv of pyruvate is liberated simultaneously, which causes time-dependent signal amplification. Pyruvate is quantified spectrophotometrically by a corresponding NADH consumption when the system is coupled to the standard pyruvate dehy-... 

Stimulation of N-methyl-D-aspartate (NMDA) receptors (see Chapter 16) in the nervous system is linked to activation of NO synthase and creation of an intracellular NO signal (Yun et al., 1998). NO can directly activate Ras protein redox modification of Ras protein is assumed to take place in this process. 

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Phenylbutazone. - This anti-inflammatory drug inhibits prostaglandin H synthase. Earlier spin-trapping studies established that PB is oxidised to a carbon-centred radical by the peroxidase activity of the enzyme.175 The radical has since been trapped with MNP upon incubation of the drug with HRP. The intensity of the signal from the adduct was reduced by GSH, suggesting chemical repair of the radical by the thiol. The PB/HRP system induced lipid peroxidation in microsomes, which was suppressed by GSH.176... 

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