Transport metabolites

Table 1. Some Metabolite Transporters in the Inner Membrane of Muscle Mitochondria... 

RB Sund, F Lauterbach. 1-Naphthol metabolism and metabolite transport in the small and large intestine. Pharmacol Toxicol 60 262-268, 1987. 

F. Wu, F. Yang, KC Vinnakota, and DA Beard, Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysio logy. J. Biol. Chem. 282(34), 24525 24537 (2007). 

PR. Wielinga, G. Reid, E.E. Challa, I. van der Heijden, L. van Deemter, M. de Haas, C. Mol, A.J. Kuil, E. Groeneveld, J.D. Schuetz, C. Brouwer, R.A. De Abreu, J. Wijnholds, J.H. Beijnen, and P. Borst. Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Mol Pharmacol. 62 1321-1331 (2002). 

Mechanism of Action An antibacterial agent that inhibits bacterial protein, RNA synthesis. Less effective on DNA synthesis. Nasal Eradicates nasal colonization of MRSA. Therapeutic Effect Prevents bacterial growth and replication. Bacteriostatic. Pharmacokinetics Metabolized in skin to inactive metabolite. Transported to skin surface removed by normal skin desquamation. 

The mechanism by which PfCRT confers resistance to chloroquine is still under discussion [75], The first aspect concerns the nature of the protein whether PfCRT, postulated to possess ten transmembrane helices, is considered as a member of the drug-metabolite transporter family of proteins [55, 76-78], Some authors discuss about the channel nature of the protein [79, 80], It has been suggested that the change of the charged lysine to uncharged threonine affects the electrostatic interaction with the diprotonated CQ [81]. In the mutated forms, the absence of electrostatic interactions allows the drug to cross the channel (Fig. 6). This results in the efflux of the drug out of the DV [81]. Note here that the reduced accumulation can be partially reversed by verapamil, a lipophilic compound (Fig. 5). 

Figure 5.6. A diagrammatic summary of adjusted hypoxia response systems (the AHRS) proposed as the ancestral physiological phenotype and as a phylogenetic adaptation to hypobaric hypoxia. Summary based largely upon studies of Quechuas and Sherpas. Essentially all of the characteristics summarized here are also expressed in individuals well adapted for endurance performance. In the latter, the main modification involves an upwards regulation of mitochondrial volume densities at the working tissues (altered expression of mitochondrial metabolic enzymes and metabolite transporters above), which is why this is referred to as a high-capacity version of the lower capacity high-altitude phenotype. See text for further details. (Modified from Hochachka et al., 1999.)...

An alternate pathway for starch synthesis has been proposed, which is based on the finding of a putative ADPGlc translocator in the envelope of both amyloplasts and chloroplasts. Akazawa et al. (1991) proposed that ADPglucose is synthesized in the cytosol by the sucrose synthase (rather than in the plastid by the action of the ADPGlc PPase, as is widely accepted), and is then transported into the plastid where it is converted into starch by the starch synthase. A critique of this hypothesis is presented in the chapter, The Site of Starch Synthesis in Nonphotosynthetic Plant Tissues The Amyloplast, where metabolite transport into the plastids is discussed, but it is worth mentioning here that this pathway does not fulfill the criteria mentioned in the preceding—that is, the experimental evidence does not support this alternative pathway. 

The rate of photosynthesis does not depend on the amount of a single component (e.g., the activity of a particular enzyme). There is a wide range of possible regulatory factors, proven to exist in vitro, but the importance of which in vivo has still to be determined. In particular, there is a multitude of factors affecting the activity of the enzymes involved, with pH, ions, coenzymes, and metabolite effectors modulating the activity of every enzyme studied thus far. Compartmentation is the other key factor. The role of metabolite transport in the cell, particularly between chloroplast and cytosol, but also to and from mitochondria, vacuole, and other organelles, is now considered to be fundamental to the regulation of photosynthesis. In this chapter, we look at the factors considered to be of major importance... 

The smahest known secondary active transporters belong to the SMR family within the drug metabolite transporter (DMT) superfamiiy (23). 

Jack DL, Yang NM, Saier MH Jr. The drug/metabolite transporter superfamily. Eur. J. Biochem. 2001 268 3620-3639. 

Note The current value of 30 molecules of ATP per molecule of glucose supersedes the earlier one of 36 molecules of ATP. The stoichiometries of proton pumping, ATP synthesis, and metabolite transport should be regarded as estimates. About two more molecules of ATP are formed per molecule of glucose oxidized when the malate-aspartate shuttle rather than the glycerol 3-phosphate shuttle is used. 

AjX often serves as a driving force for the transport of metabolites by bacteria living in fresh water, soil and intestine. On the other hand, A/2h+ was not previously reported to drive metabolite transport in extreme halophiles. 

There are proton- (or OH (-linked solute carrier systems for metabolite transport and osmotic stabilization... 

While an ATP-driven proton circuit is an experimental device with mitochondria, anaerobic mitochondria such as Strep, faecalis use the hydrolytic mode of the ATP synthase to maintain a Aju,H+ across their membrane for metabolite transport, the ATP being supplied by anaerobic glycolysis. 

In some mammalian cells, enzymes comprising partial spans of biosynthetic pathways are inside and some outside the mitochondrial matrix space. Therefore, in the liver, six mitochondrial membrane transport proteins are required for urea synthesis, three for gluconeogenesis [7,8], and three others participate in ammonia-genesis [9] in the kidney. The synthesis of neurotransmitter substances such as acetylcholine, glutamate and y-amino butyric acid requires the participation of metabolite transporters in mitochondrial membranes of nervous tissue [9,10]. 

To date, twelve transporters with different substrate specificities have been demonstrated in mammalian mitochondrial membranes - (cf.. Table 8.1). Plant mitochondria have a slightly different set [11]. Early studies of metabolite transport in mitochondria dating from the middle 1960s were concerned with identifying these transporters. More recently, research has been directed toward elucidation of molec-... 

Mitochondrial metabolite transporters (Data is taken from Refs. 6, 12 and 19)... 

In general, mechanistic studies of the mitochondrial metabolite transporters carried out in the last five years have provided evidence supporting a gated-pore, sequential model for transport. Structural studies of the adenine nucleotide carrier are more advanced than studies of the other transporters, and these provide the most clear cut evidence. 

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