Current Topics in Cellular Regulation 

About: Current Topics in Cellular Regulation is an academic journal. The journal publishes majorly in the area(s): Phosphorylation & Enzyme. It has an ISSN identifier of 0070-2137. Over the lifetime, 398 publications have been published receiving 21423 citations.

L-Glutamate Dehydrogenases*

Abstract: Publisher Summary Glutamate dehydrogenases, as a class, catalyze the reversible oxidative deamination of L-glutamate to α -ketoglutarate and ammonia The description of the characteristics of this reaction from a variety of sources show that, although all classed as glutamate dehydrogenase, the enzymes are different in terms of kinetic characteristics, metabolic function, and molecular properties The animal enzymes are sensitive to the concentration of purine nucleotides, can catalyze the reaction using either Nicotinamide adenine dinucleotide (NAD) or Nicotinamide adenine dinucleotide phosphate (NADP), and undergo a reversible polymerization reaction, which might influence the allosteric characteristics of the enzyme The non-animal sources are specific either for NAD or for NADP, are in general not influenced by purine nucleotides, and do not appear to undergo a reversible polymerization reaction These differences are related to the metabolic role of the reaction, which in animal tissues serves as an important link between carbohydrate and protein metabolism utilizing either α-ketoglutarate or glutamate depending on the condition of the cell, but which in non-animal organisms might act unidirectionally

Casein kinases--multipotential protein kinases.

Abstract: Publisher Summary Casein kinase I and casein kinase II are unique protein kinases that have been described in a number of mammalian and avian cells; an enzyme with properties similar to those of casein kinase I has been described in yeast and plants. The casein kinases prefer acidic substrates and appear to differ from the enzyme endogenous to the mammary gland. Casein kinases I and II are multipotential in the sense that a number of endogenous substrates have been identified for them. Other multipotential protein kinases include the cAMP-dependent and cGMP-dependent protein kinases and phosphorylase kinase. No physiological regulator for casein kinase I has been identified, but the enzyme requires Mg2+ for activity and is stimulated by monovalent cations; the cation requirement is similar for casein kinase II.

Thiol-based antioxidants

Abstract: The thiol redox status of intracellular and extracellular compartments is critical in the determination of protein structure, regulation of enzyme activity, and control of transcription factor activity and binding. Thiol antioxidants act through a variety of mechanisms, including (1) as components of the general thiol/disulfide redox buffer, (2) as metal chelators, (3) as radical quenchers, (4) as substrates for specific redox reactions (GSH), and (5) as specific reductants of individual protein disulfate bonds (thioredoxin). The composition and redox status of the available thiols in a given compartment is highly variable and must play a part in determining the metabolic activity of each compartment. It is generally beneficial to increase the availability of specific antioxidants under conditions of oxidant stress. Cells have devised a number of mechanisms to promote increased intracellular levels of thiols such as GSH and thioredoxin in response to a wide variety of stresses. Exogenous thiols have been used successfully to increase cell and tissue thiol levels in cell cultures, in animal models, and in humans. Increased levels of GSH and other thiols have been associated with increased tolerance to oxidant stresses in all of these systems and in some cases, with disease prevention or treatment in humans. A wide variety of thiol-related compounds have been used for these purposes. These include thiols such as GSH and its derivatives, cysteine and NAC, dithiols such as lipoic acid, which is reduced to the thiol form intracellularly, and "prothiol" compounds such as OTC, which are enzymatically converted to free thiols within the cell. In choosing a thiol for a specific function (e.g., protection of lung from oxidant exposure or protection of organs from ischemia reperfusion injury), the global effects must also be considered. For example, large increases in free thiols in the circulation are associated with toxic effects. These effects may be the result of thiyl radical-mediated reactions but could also be due to destabilizing effects of increases in thiol/disulfide ratios in the plasma, which normally is in a more oxidized state than intracellular compartments. Changes in the thiol redox gradient across cells could also adversely affect any transport or cell signaling processes, which are dependent on formation and rupture of disulfide linkages in membrane proteins. Therapeutic thiol administration has been shown to have great potential, and its efficacy should be increased by selecting compounds and methods of delivery that will minimize perturbations in the thiol status of regions external to the targeted areas.

The role of cyclic-AMP-dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle.

Abstract: Publisher Summary This chapter discusses the role of cyclic-AMP-dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle. When assayed at optimal ATP-Mg-concentrations and in the presence of saturating amounts of Ca2+, purified phosphorylase kinase has a very low activity at physiological pH (6.8) relative to the activity at pH 8.2. Phosphorylation of α subunit of phosphorylase kinase controls the rate of dephosphorylation of the β subunit catalyzed by phosphorylase kinase phosphatase. The conversion of phosphorylase kinase a to phosphorylase b correlates with dephosphorylation of the β subunit, and the rate of dephosphorylation of the enzyme in the absence of divalent cations is determined by the extent of phosphorylation of the α subunit. Phosphorylation of the α subunit alters the conformation of phosphorylase kinase in such a way that it facilitates the action of phosphorylase kinase phosphatase on the β subunit. Cyclic-AMP-dependent protein kinase plays two roles: (1) it activates the enzyme through phosphorylation of the β subunit and (2) it determines the time at which dephosphorylation of the β subunit and inactivation of the enzyme can become rapid through phosphorylation of the α subunit.

Cellular thiols and redox-regulated signal transduction.

Abstract: In contrast to the conventional notion that reactive oxygen is mostly a trigger for oxidative damage of biological structures, now we know that low physiologically relevant concentrations of ROS can regulate a variety of key molecular mechanisms that may be linked with important cell functions (Fig. 4). Redox-based regulation of gene expression has emerged as a fundamental regulatory mechanism in cell biology. Several proteins, with apparent redox-sensing activity, have been described. Electron flow through side-chain functional CH2-SH groups of conserved cysteinyl residues in these proteins account for the redox-sensing properties. Protein thiol groups with high thiol-disulfide oxidation potentials are likely to be redox-sensitive. The ubiquitous endogenous thiols thioredoxin and glutathione are of central importance in redox signaling. Signals are transduced from the cell surface to the nucleus through phosphorylation and dephosphorylation chain reactions of cellular proteins at tyrosine and serine/threonine. Protein phosphorylation, one of the most fundamental mediators of cell signaling, is redox-sensitive. DNA-binding proteins are involved in the regulation of cellular processes such as replication, recombination, viral integration and transcription. Several studies show that the interaction of certain transcription regulatory proteins with their respective cognate DNA sites is also redox-regulated. Changes in the concentration of Ca2+i control a wide variety of cellular functions, including transcription and gene expression; Ca(2+)-driven protein phosphorylation and proteolytic processing of proteins are two major intracellular events that are implicated in signal transduction from the cell surface to the nucleus. Intracellular calcium homeostasis is regulated by the redox state of cellular thiols, and it is evident that cell calcium may play a critical role in the activation of the redox-sensitive transcription factor NF-kappa B. Among the several thiol agents tested for their efficacy in modulating cellular redox status, N-acetyl-L-cysteine and alpha-lipoic acid hold most promise for human use. A strong therapeutic potential of strategies that would modulate the cellular thioredoxin system has been also evident.