Enzyme activity signal transduction

One main line of future research could be in the inhibitory/activating effect on key enzymes involved in the pathogenesis of arteriosclerosis. In particular, enzymes regulating signal transduction involved in phosphorylation of proteins, such as PKC and tyrosine protein kinase, seems to be somehow modulated by different polyphenols and may represent a possible target for polyphenol activity. 

PLC is a generic name for a family of isoforms of an enzyme which remain membrane bound as the presence of phospholipids is required for activity. Signal transduction via PLC as the effector is mediated by not one but two second messengers inositol 1,4,5 triphosphate (IP3) and DAG, which are the products of hydrolysis of membrane phospholipid by PLC (Figure 4.18). 

The phosphorylation and dephosphorylation of seryl, threonyl, and tyrosyl residues regulate the activity of certain enzymes of lipid and carbohydrate metabolism and the properties of proteins that participate in signal transduction cascades. 

Fig. 3. A proposed signal transduction pathway regarding the external Ca effect on ginsenoside Rb synthesis by P. notoginseng cells. Ca signal changes are triggered by external Ca concentrations. The calcium signatures are decoded by calcium sensors, CaM and CDPK. UGRdGT is possibly modulated by the sensors in a direct or indirect (dashed lines) way. Changes of CDPK activity may result from increased synthesis or posttranslational modification of the enzyme (shown as CDPK ).

Most biological reactions fall into the categories of first-order or second-order reactions, and we will discuss these in more detail below. In certain situations the rate of reaction is independent of reaction concentration hence the rate equation is simply v = k. Such reactions are said to be zero order. Systems for which the reaction rate can reach a maximum value under saturating reactant conditions become zero ordered at high reactant concentrations. Examples of such systems include enzyme-catalyzed reactions, receptor-ligand induced signal transduction, and cellular activated transport systems. Recall from Chapter 2, for example, that when [S] Ku for an enzyme-catalyzed reaction, the velocity is essentially constant and close to the value of Vmax. Under these substrate concentration conditions the enzyme reaction will appear to be zero order in the substrate. 

FIGURE 8.11 Multiple signal-transduction pathways initiated by calmodulin. Calmodulin bound to Ca2+ interacts and activates many enzymes, opening up a wide range of possible cellular responses. Abbreviations MAP-2, microtubule-associated protein 2 NO, nitric oxide Tau, tubulin assembly unit. 

One of the principal rules of biochemical regulation is, When you turn something on, be sure that you have a way to turn if off. Signal transduction pathways are no different. Kinases are opposed by phosphatases. These enzymes simply hydrolyze the tyrosine or serine/threo-nine phosphate. Because they are in opposition, activation of the phosphatase (there are pathways for this too) is similar to inactivation of the opposing kinase. Often the two activities are coordinate regulated... 

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