Cell/cellular metabolism

FIGURE 5.3 Different types of functional readouts of agonism. Receptors need not mediate cellular response but may demonstrate behaviors such as internalization into the cytoplasm of the cell (mechanism 1). Receptors can also interact with membrane proteins such as G-proteins (mechanism 2) and produce cytosolic messenger molecules (mechanism 3), which can go on to mediate gene expression (mechanism 4). Receptors can also mediate changes in cellular metabolism (mechanism 5). 

Methotrexate belongs to the class of antimetabolites. As a derivative of folic acid it inhibits the enzyme dihydrofolate reductase resulting in a decreased production of thymidine and purine bases essential for RNA and DNA synthesis. This interruption of the cellular metabolism and mitosis leads to cell death. 

Metabolic diseases In the pancreatic (3-cells, KATP channel derived from >SUR1 and Kir6.2, links cellular metabolism to electrical activity and regulates insulin secretion. Mutations in SUR1 and Kir6.2 that result in loss of Katp channel function have been identified in families with familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI). 

FIGURE 49-1. Normal glucose metabolism. Once insulin binds with receptors on the cell membrane, glucose can move into the cell, promoting cellular metabolism and energy production. 

Panthenol is the alcohol form of pantothenic acid, more familiar as vitamin B5. In a living cell, panthenol is converted to pantothenic acid, which then becomes an important part of the compound coenzyme A, which is important in cellular metabolism. In hair, which contains no living cells, it remains panthenol. 

Deprived of their substrate in severe or prolonged hypoxia, some ATPase-driven systems, including ion pumps, may become impaired. Further, with the decrease in the availability of O2 as its terminal electron acceptor, the mitochondrial transport chain becomes increasingly unable to accept reducing equivalents from cellular metabolic processes. Hence the intracellular pH falls, subjecting the cell as a whole to a reductive stress and favouring those enzyme systems with acid pH optima. 

Interferon-a2b has diverse mechanisms of action, including antiviral activity, impact on cellular metabolism and differentiation, and antitumor activity.42 The antitumor activity is due to a combination of direct antiproliferative effect on tumor cells and indirect immune-mediated effects.42 Interferon-a2b is currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for patients who are free of disease after curative surgical resection but are at high risk of MM recurrence. This includes patients with bulky disease or regional lymph node involvement such as stage IIB, IIC, or III disease.43 It is controversial if interferon-a2b (IFN) should be offered as adjuvant therapy for every high-risk MM patient. The reason is because clinical trials with different doses of IFN have not proved definitively that IFN improves overall patient survival. 

Potassium is the second most abundant cation in the body and is found primarily in the intracellular fluid. Potassium has many important physiologic functions, including regulation of cell membrane electrical action potential (especially in the myocardium), muscular function, cellular metabolism, and glycogen and protein synthesis. Potassium in PN can be provided as chloride, acetate, and phosphate salts. One millimole of potassium phosphate provides 1.47 mEq of elemental potassium. Generally, the concentration of potassium in peripheral PN (PPN) admixtures should not exceed 80 mEq/L (80 mmol/L). While it is safer to also stick to the 80 mEq/L (80 mmol/L) limit for administration through a central vein, the maximum recommended potassium concentration for infusion via a central vein is 150 mEq/L (150 mmol/L).14 Patients with abnormal potassium losses (e.g., loop or thiazide diuretic therapy) may have higher requirements, and patients with renal failure may require potassium restriction. 

The effect of the material on cellular metabolism is also an important measure of biocompatibility. To determine such effects, cultured ex vivo cells can be exposed to the polymer and the growth rates compared to controls [216,217], The metabolic function of the cells can be tested by assay for production of a marker enzyme. An additional advantage of this type of test is that it avoids the use of live animals. 

Figure 10.1 ThecyclicAMPsecondmessengersystem.Themostcommonsecond messenger system activated by the protein/peptide hormones and the catecholamines involves the formation of cAMP. This multistep process is initiated by binding of the hormone (the first messenger) to its receptor on the cell surface. The subsequent increase in the formation of cAMP (the second messenger) leads to the alteration of enzyme activity within the cell. A change in the activity of these enzymes alters cellular metabolism.

The carbon dioxide produced during cellular metabolism diffuses out of the cells and into the plasma. It then continues to diffuse down its concentration gradient into the red blood cells. Within these cells, the enzyme carbonic anhydrase (CA) facilitates combination of carbon dioxide and water to form carbonic acid (H2C03). The carbonic acid then dissociates into hydrogen ion (H+) and bicarbonate ion (HC03). 

Such a plethora of radicals produced as a result of normal cellular metabolism needs to be rapidly scavenged by cytoprotective enzymes and antioxidants present in the cell and cellular membranes, both hydrophobic and hydrophilic compartments. The... 

Both the overall rate of protein synthesis and the translation of certain specific mRNAs are controlled by agents such as hormones, growth factors, and other extracellular stimuli. As precursors for protein assembly, amino acids also regulate the translational machinery. Because protein synthesis consumes a high proportion of cellular metabolic energy, the energy status of the cell also modulates translation factors. 

The principal controls on the microbial reaction rate in our example, then, are biomass and thermodynamic drive (Fig. 33.2). Initially, in the presence of abundant lactate and arsenate, the rate is controlled by the size of the microbial population available to catalyze lactate oxidation. As the population increases, so does reaction rate. Later, as reactants are consumed and products accumulate, the reaction approaches the point at which the energy liberated by its progress is balanced by that needed in the cell to synthesize ATR Reaction rate is governed now by the energy available to drive forward the cellular metabolism, this energy represented by the thermodynamic potential factor Ft over the course of the experiment, the kinetic factors Fd and Fa play minor roles. 

Surprisingly, GHB is naturally present in most cells of the human body at very low concentrations. Although the function of the body s own GHB is not clear, scientists believe it may be involved with cellular metabolism. GHB is also found in the brain and is believed to act as a neurotransmitter. It is believed... 

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