Effector enzymes

Ad values) (4) effect on the pH function of any or all components of the reactions (including the buffer) (5) effect on the affinity(ies) of enzyme effector(s) (6) an alteration in the rate determining (or rate contributing) step(s) (7) effect on the coupling enzymes of the assay and (8) effect on physical properties e.g., solubility of substrates, particularly gas substrates such as O2 and N2, dielectric constant of the solvent, etc.). 

Free or uncomplexed enzyme General symbol for enzyme Effector molecule... 

Following cannabinoid binding, multiple signaling pathways can be activated Gij0jS-protein mediated modulation of adenylate cyclase and cAMP levels Ca2+ and K+ ion channel activation or activation of different intracellular enzymes/effectors (i.e., kinases, ceramide) in a non-G-protein dependent manner (Childers et al., 1993 Felder et al., 1995 Mackie et al., 1995 Prather et al., 2000 Sanchez et al., 2001). 

Source of enzyme effector added Substrate reduction Source of enzyme effector added Substrate reduction ... 

Competition between enzymes for common substrates and cosubstrates on the basis of their Michaelis constants product inhibition stoichiometric effects of metabolites on equilibria and reaction rates changes in the type and quantity of enzyme effectors. 

The single theme that continually recurs in all studies of the cellular mechanism of action of retinoids is that they modify cell differentiation and cell proliferation. However extensive the data that we have just summarized on the effects of retinoids on individual cellular enzymes, effectors, structural proteins, or glycoconjugates, they fail to provide a satisfactory explanation of the molecular mechanism of action of retinoids because they fail to consider the central role of the genes of the cell in control of differentiation and proliferation. Ultimately, it would appear that the problem of the molecular mechanism of action of... 

Molybdate is also known as an inhibitor of the important enzyme ATP sulfurylase where ATP is adenosine triphosphate, which activates sulfate for participation in biosynthetic pathways (56). The tetrahedral molybdate dianion, MoO , substitutes for the tetrahedral sulfate dianion, SO , and leads to futile cycling of the enzyme and total inhibition of sulfate activation. Molybdate is also a co-effector in the receptor for steroids (qv) in mammalian systems, a biochemical finding that may also have physiological implications (57). 

The basic kinetic properties of this allosteric enzyme are clearly explained by combining Monod s theory and these structural results. The tetrameric enzyme exists in equilibrium between a catalytically active R state and an inactive T state. There is a difference in the tertiary structure of the subunits in these two states, which is closely linked to a difference in the quaternary structure of the molecule. The substrate F6P binds preferentially to the R state, thereby shifting the equilibrium to that state. Since the mechanism is concerted, binding of one F6P to the first subunit provides an additional three subunits in the R state, hence the cooperativity of F6P binding and catalysis. ATP binds to both states, so there is no shift in the equilibrium and hence there is no cooperativity of ATP binding. The inhibitor PEP preferentially binds to the effector binding site of molecules in the T state and as a result the equilibrium is shifted to the inactive state. By contrast the activator ADP preferentially binds to the effector site of molecules in the R state and as a result shifts the equilibrium to the R state with its four available, catalytically competent, active sites per molecule. 

Regulatory or allosteric enzymes like enzyme 1 are, in some instances, regulated by activation. That is, whereas some effector molecules such as F exert negative effects on enzyme activity, other effectors show stimulatory, or positive, influences on activity. 

The working hypothesis is that, by some means, interaction of an allosteric enzyme with effectors alters the distribution of conformational possibilities or subunit interactions available to the enzyme. That is, the regulatory effects exerted on the enzyme s activity are achieved by conformational changes occurring in the protein when effector metabolites bind. 

First draw both Lineweaver-Burk plots and Hanes-Woolf plots for the following a Monod-Wyman-Changeux allosteric K enzyme system, showing separate curves for the kinetic response in (1) the absence of any effectors (2) the presence of allosteric activator A and (3) the presence of allosteric inhibitor I. Then draw a similar set of curves for a Monod-Wyman-Changeux allosteric Uenzyme system. 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

CC, and one CX3C and XC chemokine receptors have been cloned so far [2]. Receptor binding initiates a cascade of intracellular events mediated by the receptor-associated heterotrimeric G-proteins. These G-protein subunits trigger various effector enzymes that lead to the activation not only of chemotaxis but also to a wide range of fimctions in different leukocytes such as an increase in the respiratory burst, degranulation, phagocytosis, and lipid mediator synthesis. 

NO-sensitive GC represents the most important effector enzyme for the signalling molecule NO, which is synthesised by NO synthases in a Ca2+-dependent manner. NO-sensitive GC contains a prosthetic heme group, acting as the acceptor site for NO. Formation of the NO-heme complex leads to a conformational change, resulting in an increase of up to 200-fold in catalytic activity of the enzyme [1]. The organic nitrates (see below) commonly used in the therapy of coronary heart disease exert their effects via the stimulation of this enzyme. 

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