Metabolism compartmentation and

Berl, S. and Clarke, D. D. Introduction. In S. Berl, D. D. Clarke andD. Schneider (eds),Metabolic Compartmentation and Neurotransmission Relation to Brain Structure and Function. New York Plenum Press, 1975, pp. xiii-xvii. 

Ho SY, Delgado L, Storch J (2002) Monoacylglycerol metabolism in human intestinal Caco-2 cells evidence for metabolic compartmentation and hydrolysis. J Biol Chem 277 1816-1823... 

Cremer J E, Heath D F, Patel A. J., Balazs R, and Cavanagh J B (1975) An Experimental Model of CNS Changes Associated with Chronic Liver Disease Portocaval Anastomosis in the Rat, m Metabolic Compartmentation and Neurotransmisswn (Berl S, Clarke D.D, and Schneider D, eds ), pp 461-478, Plenum, New York... 

McKenna,M. C.,Stevenson,J. H.,Huang,X. etal. Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem. Int. 37 229-241, 2000. 

It is generally accepted that chloroplasts possess an intact pathway of aromatic amino acid biosynthesis that is tightly regulated. In addition, the subcellular location of some aromatic-pathway isozymes has been shown to be in the cytosol, but whether an intact pathway exists in the cytosol has not yet been proven. The evidence bearing on aromatic amino acid compartmentation and regulation is reviewed, with particular emphasis given to the relationship between primary biosynthesis and secondary metabolism in the cytosol. 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

FIGURE 21-8 Subcellular localization of lipid metabolism. Yeast and vertebrate cells differ from higher plant cells in the compartmentation of lipid metabolism. Fatty acid synthesis takes place in the compart-... 

Ovadi J, Saks V. 2004. On the origin of intracellular compartmentation and organized metabolic systems. Molec Cel Biochem 256/257 5-12. 

The classical compartmental and more complex PBPK models require actual pharmacokinetic data to calibrate some parameters such as metabolic rate constants. However, PBPK models are more data-intensive and require greater numbers of chemical-specific and receptor-specific inputs. Although PBPK models have been used extensively in the last 20 years to address cross-species differences and other uncertainties, there are cases in which simpler one- or two-compartment models have been sufficient for risk assessment, for example for methyl mercury (EPA 2001). 

Re, D. B., Nafia, I., Melon, C., Shimamoto, K., Kerkerian-Le Goff, L., and Had-Aissouni, L. (2006). Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport. Glia 54,... 

Liu K-C, Boyer CD, Shannon JC. In Huang A, Taiz L, eds. Molecular Approaches to Compartmentation and Metabolic Regulation. Rockville, Maryland American Society of Plant Physiologists 1991 236. 

Wiemken, A., Frehner, M., Keller, F., and Wagner, W., Fructan metabolism enzymology and compartmentation, Curr. Topics Plant Biochem. Physiol., 5, 17-37, 1986. 

Biotinidase activity in cerebrospinal fluid and the brain is very low. This suggests that the brain may not recycle biotin effectively and depends on biotin transported across the blood-brain barrier. Several symptomatic children who have failed to exhibit peripheral lactic acidosis or organic aciduria have had elevated lactate or organic acids in their cerebrospinal fluid. This compartmentalization of the biochemical abnormalities may explain why the neurological symptoms usually appear before other symptoms. Peripheral metabolic ketoacidosis and organic aciduria subsequently occur with prolonged metabolic compromise. 

For pharmacokinetics in plasma Individual concentrations of XYZ1234 will be tabulated together with descriptive statistics and plotted. Median profiles will be presented graphically by CYP 2C19 metabolizer status and gender. Pharmacokinetic parameters (at least Cmax, tmax, AUC(o-t) [t = 24 h and last > LOQ ], AUCinf, ti/2z, MT, as well as CL/f and Vz/f) will be determined based on plasma concentrations of X YZ1234 using non-compartmental procedures. 

Biosynthesis of IAA from tryptophan uses the L-form of the amino acid.75 Some of the enzymes that catalyze the conversion of specific intermediates have been identified, and some of the genes coding for the enzymes have been cloned. Such findings establish that plants are competent to carry out such metabolic conversions however, the specific involvement of these genes and intermediates requires confirmation, because biochemical studies carried out with applications to tissue segments or with extracts could disrupt tissue and cellular compartmentalization and because enzymes that catalyze the conversion of tryptophan to IAA in vitro may never come into contact with the intermediates in vivo. Thus, the physiological relevance of some of these pathways remains an open question.69 An additional concern is that many of the enzymes have wide substrate specificities, so it has been difficult to implicate them solely in IAA biosynthesis. Some of the intermediates and enzymes that have been described to have the competence to carry out these reactions are discussed below. 

Akazawa, T., Pozueta-Romero, J., and Ardila, F. 1991. New aspects of starch biosynthesis in the plant cell. In Compartmentation and Metabolic Regulation (A. H. C. Huang and L. Taiz, eds.), pp. 74-85. American Society of Plant Physiologists, Rockville, MD. 

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