Metabolic regulation intracellular

Microtubules may function as a form of skeletal support for microfilaments. Agents that increase intracellular cGMP favour the assembly of microtubules, whereas those that increase intracellular Ca2+ and cAMP result in the dissolution of tubulin fibres. Furthermore, the oxidation state of the neutrophil may affect the integrity of the tubulin fibres. Oxidised glutathione (which is increased during oxidative metabolism) regulates tubulin disassembly, and oxidation may increase tubulin tyrosylation, which also promotes disassembly. 

The intracellular CER concentration results from the equilibrium between CER production and CER metabohsm It now appears that CER metabolism plays a critical role in regulating intracellular CER concenttation and therefore effector-induced cytotoxicity. The four major CER metabolic pathways include its reconversion into SM, its catabohsm to sphingosine (followed by sphingosine 1-phosphate) and its metabolism to glucosylceramide or galactosylceramide. All of which may conttibute to limiting stress-induced CER elevation, except for the galactosylceramide pathway which has of yet not been described. 

Intracellular carnosine concentration may be subject to metabolic regulation. Destruction of the dipeptide by camosinase is stimulated by citrate (Vistoli et al., 2006), thus raising the possibility that inhibitory molecules could be created to prevent destruction of the dipeptide in sera. Camosine s synthesis by carnosine synthetase is downregulated by raised cAMP levels (Schulz et al., 1989), at least in astrocytes. Thus, high glucose concentrations could lower cAMP levels and hence stimulate carnosine synthesis. 

The role of internal hydration as a signal for cellular function may be recognized by analogy to metabolic regulation by [Ca2+] or pH . Cells possess efficient mechanisms that keep the intracellular calcium and proton concentrations within narrow limits, otherwise cells would not survive. These homeostatic mechanisms can also be used to produce small physiological changes in cell hydration, which, in turn, regulate cell function. 

To recapitulate, the situation arising from these studies of oxygen and metabolic regulation can be summarized as follows. First, because of the buffering role of Mb, oxygen concentrations are low (in the P50 or Kd range) and intracellular [02] gradients must be quite shallow. Second, it is emphasized by the... 

FABPs have been implicated in transmembrane and intracellular transport of fatty acids (Veerkamp et al., 1991 Storch and Thumser, 2000). These are a group of tissue-specific proteins of about 14-15 kDa that bind long-chain fatty acids (C16-C20) with high affinity and a molar stoichiometry of 1 1. Most bind unsaturated fatty acids with higher affinity than saturated fatty acids. In addition to transport functions it has been proposed that they modulate specific enzymes of lipid metabolism, regulate expression of fatty acid-responsive genes, maintain cellular membrane fatty acid levels, and reduce the concentration of fatty acids in the cell, thereby removing their inhibitory effect on metabolic processes. 

Hormones regulate intracellular metabolic processes. Insulin intensifies transfer (transport) of the glucose in the cell and decreases its level in the circulating blood. Glucagon increases the sugar level in the blood. The two hormones are synthesized by the pancreas. Antibodies discern foreign bodies in an organism. 

The maintenance of cellular homeostasis implies the dynamic coordination of cellular processes to finely compensate for subtle variations of the external and internal environments (e.g., pH, osmolarity, nutrients, and oxygen supply) but also to monitor and regulate intracellular signalling and compartmentalization. Cellular stress occurs when a threat to homeostasis is detected by highly reactive and efficient protective mechanisms. Depending on the intensity (dose) and duration (exposure) of the stress, these defenses can either cope without any observable change in cellular homeostasis or be overcome, resulting in a detectable shift from basal metabolic or cellular functions. 

It has long been recognised that metabolites, and metabolic activities, are distributed non-uniformly within cells. Such compartmentation is undoubtedly an important aspect of metabolic regulation. The accurate quantitation of metabolite levels in various intracellular compartments represents a major stumbling block in the study of metabolic regulation. There are two aspects to the study of metabolite compartmentation by in vivo NMR. The first, and most problematic, is the assignment of resonances to specific intracellular compartments we focus on this aspect here. The second is the use of NMR spectroscopic parameters (e.g., intensity, chemical shift) to monitor conditions (e.g., pH, concentrations, fluxes) within specific compartments, using methods outlined in other sections of this chapter. 

Busa, W. B. Nuccitelli, R. (1984). Metabolic regulation via intracellular pH. Am. J. Physiol. 246, R409-R438. 

MEMBRANE TRANSPORT Membrane transport mechanisms are vital to living organisms. Ions and molecules constantly move across cell plasma membranes and across the membranes of organelles. This flux must be carefully regulated to meet each cell s metabolic needs. For example, a cell s plasma membrane regulates the entrance of nutrient molecules and the exit of waste products. Additionally, it regulates intracellular ion concentrations. Because lipid bilayers are generally impenetrable to ions and polar substances, specific transport components must be inserted into cellular membranes. Several examples of these structures, referred to as transport proteins or permeases, are discussed. 

The regulation of protein phosphatases is intimately related to that of protein kinases, both being part of an overall cycle that acts as a switching mechanism to turn-on or turn-off certain enzyme activities. Within the past decade, at least 20 publications have described the involvement of Mn(II) with these systems. Most notably, these include the following protein-specific enzymes phosphorylase phosphatase [87,104], Ga/calmod-ulin-dependent protein phosphatase [94,99,105-107], and calcineurin phosphatase [91,93,95], each being involved in intracellular signalling and metabolic regulation. 

D. F. Wilson, Regulation of cellular metabolism by intracellular phosphate, Bioohlm. Blophvs. 

Fig. 4.22. Hypoxia-mediated metabolic adaptation for energy preservation. Activation of genes for glucose transporter-1 (GLUT-1 = 1) and glycolytic enzymes yields an increased glycolytic rate. H -ions produced are preferentially exported via a Na /H -antiporter (NHE-1 = 3) and a lactate /H -symporter (monocarboxylate transporter MCT-1 = 2) leading to a drop in extracellular pH (pH.). Low extracellular pH activates the membrane-bound ectoenzyme carbonic anhydrase IX (CA IX = 4). Key mechanism regulating intracellular pH in tumor cells when protons are produced is also shown (Na -depen-dent HCOs" /CL -exchanger = 5). HIF-Ia = hypoxia-inducible factor la, PHDs = prolyl hydroxylases, FIH = asparagyl hydroxylase, lac" = lactic acid...

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