Metabolism intracellular

Permeation of a drug through biological membranes against the electrochemical gradient. This type of drug transport requires energy produced by intracellular metabolic processes. 

Blum AS, Dal Pan GJ et al (1996) Low-dose zalcitabine-related toxic neuropathy frequency, natural history, and risk factors. Neurology 46(4) 999-1003 Bradley WG, Verma A (1996) Painful vascuhtic neuropathy in HlV-1 infection relief of pain with prednisone therapy. Neurology 47(6) 1446-1451 Breen EC (2002) Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome. Pharmacol Ther 95(3) 295-304 Bremer J (1990) The role of carnitine in intracellular metabolism. J Clin Chem Clin Biochem 28(5) 297-301... 

Balzarini J, Hao Z, Herdewijn P, Johns DG, De Clercq E. Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylme-thoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. Proc Natl Acad Sci USA 1991 88 1499-1503. 

A simple steady-state model is presented for simultaneous passive diffusion and intracellular metabolism of a drug undergoing the irreversible reaction... 

Figure 28 The biophysical model for passive diffusion and concurrent intracellular metabolism of a drug for a simple A-to-B reaction process. Concentration-distance profiles are depicted in the aqueous boundary layer and intracellular domain for the drug and metabolite. The bottom diagram depicts the direction of the fluxes of drug and metabolite viewed from the donor and receiver sides of the cell monolayer. Details of basic assumptions are found in the text.

Williams, A.W., Boileau, T.W., Zhou, J.R., Clinton, S.K., and Erdman, J.W. Jr. 2000 Beta-carotene modulates human prostate cancer cell growth and may undergo intracellular metabolism to retinol. J Nutr 130 728-732. 

Assessing the effect of the intestinal metabolism in the Peff as a membrane transport rate parameter is a methodological issue [7, 26, 34, 35, 49]. An evaluation of its influence has to include a study to establish which enzyme(s) is (are) involved and the site of metabolism in relation to the site of the measurements. Intracellular metabolism in the enterocyte, for instance by CYP 3A4 and di- and tri-... 

Fig. 7.16. Ketoconazole had no effect on human effective in vivo permeability (Pefr) of R/S-verapamil, antipyrine, and D-glucose. The data suggest that extensive intracellular metabolism (in the enterocyte mediated by CYP 3A4) of substrates such as R/S-verapamil...

Hemolytic anemia results from decreased RBC survival time due to destruction in the spleen or circulation. The most common etiologies are RBC membrane defects (e.g., hereditary spherocytosis), altered Hb solubility or stability (e.g., sickle cell anemia [see Chap. 34] and thalassemias), and changes in intracellular metabolism (e.g., glucose-6-phosphate dehydrogenase deficiency). Some drugs cause direct oxidative damage to RBCs (see Appendix 3). 

Knowledge of receptors explains how cells know there is an incoming signal but does not explain the metabolic consequences of hormone activation. Transduction is the conversion of the external signal message, into a sequence of intracellular metabolic... 

Since transport across the syncytiotrophoblast layer is the rate-limiting step in the absorption of substances from the maternal circulation to the fetal, these cells can provide information on uptake processes which are subject to intracellular regulatory mechanisms or affected by intracellular metabolism. However, it is very difficult to isolate this layer because of its syncytial nature. As a result, the undifferentiated precursor cytotrophoblast cells have been isolated and cultured. These cells do not proliferate in culture, but aggregate and spontaneously differentiate into syncytiotrophoblasts [49],... 

During the last ten years, it has become apparent that calcium-dependent papain-like peptidases called calpains (EC 3.4.22.17) represent an important intracellular nonlysosomal enzyme system [35][36], These enzymes show limited proteolytic activity at neutral pH and are present in virtually every eukaryotic cell type. They have been found to function in specific proteolytic events that alter intracellular metabolism and structure, rather than in general turnover of intracellular proteins. Calpains are composed of two nonidentical subunits, each of which contains functional calcium-binding sites. Two types of calpains, i.e., /i-calpain and m-calpain (formerly calpain I and calpain II, respectively), have been identified that differ in their Ca2+ requirement for activation. The activity of calpains is regulated by intracellular Ca2+ levels. At elevated cytoplasmic calcium concentrations, the precursor procal-pain associates with the inner surface of the cell membrane. This interaction seems to trigger autoproteolysis of procalpain, and active calpain is released into the cytoplasm [37]. 

Figure 2. Possible reactions during intracellular metabolism of a quinone.

Studied in both an experimental and theoretical manner. The link between glycolytic oscillations and the pulsatile secretion of insulin in pancreatic p cells [53] is another topic of current concern. Models for the latter phenomenon rely on the coupling between intracellular metabolic oscillations and an ionic mechanism generating action potentials. Such coupling results in bursting oscillations of the membrane potential, which are known to accompany insulin secretion in these cells [54, 55]. 

A paper published six decades ago was the first to draw attention to the possibility that a change in the rate of transport of a molecule across the plasma membrane conld play a role in regulation of both intra- and extracellnlar metabolism that is, the regulation of the blood glncose level and the intracellular metabolism of glucose. The paper was entitlied A hypothesis of insulin action is proposed which attributes to insulin the role of facilitating the rate of transport of some hexoses into the cell as opposed to a direct effect on intracellular metabolism (Levine et al. 1950). 

In an attempt to explain the reason for the delay in the onset of the therapeutic effect of antidepressants, which is clearly unrelated to the acute actions of these drugs on monoamine reuptake transporters or intracellular metabolizing enzymes, emphasis has moved away from the presynaptic mechanism governing the release of the monoamine transmitters to the adaptive changes that occur in pre- and postsynaptic receptors that govern the physiological expression of neurotransmitter function. 

Metabolism - Methotrexate undergoes hepatic and intracellular metabolism. The terminal half-life reported is approximately 3 to 10 for patients receiving treatment for psoriasis, RA, or low-dose antineoplastic therapy (less than 30 mg/m ). 

Mathematical optimization always requires a deterministic process model to predict the future behavior of a process. However, as previously mentioned, it is difficult to construct mathematical models that can cover the entire range of fermentation due to the complexity of intracellular metabolic reactions. As an alternative to the deterministic mathematical models, Kishimoto et al. proposed a statistical procedirre that uses linear multiple regression models [7], as shown below, instead of a deterministic mathematical model such as a Monod equation. 

Recent reviews pertaining to such topics as the role of calcium in growth control (82), lectins as natural membrane components (83), fibronectins (84), and biochemical studies of the cell cycle (85, 86, 87, 88), together with many of the works cited earlier, suggest a dynamic, time-dependent relationship between extracellular factors, membrane components and the intracellular metabolic machinery as a cell goes from... 

J. Heeren and U. Beisiegel, Intracellular metabolism of triglyceride-rich lipoproteins, Curr. Opin. Lipidol. 12 (2001) 255-260. 

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