Nucleotide transporter

Figure 12-11. Combination of phosphate transporter ( ) with the adenine nucleotide transporter ((2)) in ATP synthesis. The H+ZP, symport shown is equivalent to the P /OH antiport shown in Figure 12-10. Four protons are taken into the mitochondrion for each ATP exported. However, one less proton would be taken in when ATP is used inside the mitochondrion.

The chemi-osmotic theory of oxidative phosphorylation has been reviewed,74 a model for mitochondrial oxidative phosphorylation in which a membrane potential or proton gradient might transmit energy from an oxidation step to ATP synthesis has been proposed,76 and adenine nucleotide transport in mitochondria has been reviewed.76... 

The adenine nucleotide transporter is known as a translocase - it transports ADP into and ATP out of the mitochondrion in such a way that, when one molecule of ADP is transported in, one molecule of ATP is transported out... 

A nucleotide transporter (located in the outer mitochondrial membrane) that mediates one-for-one transloca-tion/exchange of cytosolic ADP for mitochondrial ATP. This translocase is potently inhibited by atractyloside and bonkregic acid. 

Krai, V., Sessler, J. L., Furuta, H., Synthetic sapphyrin cytosine conjugates - carriers for selective nucleotide transport at neutral Ph. J. Am. Chem. Soc. 1992, 114, 8704-8705. 

Exceptions from Lipinski s rule, i.e., molecules of PSA values > 140 A2 are found to be actively absorbed by carrier-mediated transport systems (Wessel et al. 1998), as shown in Fig. 3. IB. As further detailed in Fig. 3.2, the intestinal epithelium expresses a number of such transport systems for amino acids, organic anions and cations, nucleosides, and hexoses. Among these systems are the apical sodium-dependent bile acid transporter (ASBT Annaba et al. 2007), the monocarboxylate transporter (MCT Halestrap and Price 1999), the sodium-D-glucose co-transporter (SFGT1 Kipp et al. 2003), and the nucleotide transporter SPNT1 (Balimane and Sinko 1999). In addition, the expression of a specialized transporter system for small peptides has been found in the intestinal epithelium with the di/tripeptide transporter, PepTl (Tsuji 2002), after previous functional studies by Hu et al. (1989), and the cloning of PepTl... 

According to the methanochondrion concept ATP is synthesized by A/iH across internal membranes and ATP is transported from the organelle into the cytoplasm via an ATP/ADP translocator (for a cartoon see ref [162]). Thus, the observed uncoupler insensitivity of ATP synthesis might be explained on the assumption that the internal membranes are not accessible to these compounds. However, upon reinvestigation of the electron microscopic data and the adenine nucleotide transport this explanation could be ruled out the internal membranes which had been described in the literature for Methanobacterium thermoautotrophicum were found to be artefacts of fixation [163] (see also ref [164]). The adenine nucleotide transport could be explained by a tight and... 

The activity of this transporter which catalyzes net movements of adenine nucleotides is mentioned here in connection with the electrogenic adenine nucleotide exchange carrier, although it is likely to be a proton-compensated electroneutral exchanger. No counter ion has been identified, nor have compensating proton movements been reported in conjunction with the net nucleotide transport. Also, no influence of ApH on steady state total nucleotide levels has been reported. 

Not all the transporters discussed above are present in aU types of mitochondria the set of activities present in mitochondria depends on the functional needs of the cells from which the mitochondria are isolated. The adenine nucleotide and phosphate transporters are present in all mitochondria thus far studied. This reflects the fact that the major function of mitochondria is the synthesis of ATP. Even in the rare instances (e.g., brown fat mitochondria [55] and mitochondria in anaerobically growing yeast [56]) where the major function is not ATP synthesis, mitochondria normally have active adenine nucleotide transport. The pyruvate transporter also appears to be ubiquitous. The carnitine transporter has been studied in liver [57], heart [35] and sperm [58] and is probably present in all mitochondria which use long-chain fatty acids. 

Although a few subunits of mitochondrial membrane proteins are coded by mitochondrial DNA and synthesized in the mitochondrial matrix, most membrane proteins including the adenine nucleotide carrier are coded by nuclear genes and synthesized on cytoplasmic ribosomes [80,81], Chloramphenicol, an inhibitor of mitochondrial protein synthesis, does not inhibit incorporation of radioactive leucine into the carrier in growing Neurospora crassa, but cycloheximide, an inhibitor of cytoplasmic protein synthesis, does inhibit leucine incorporation [78]. Also, a yeast nuclear respiratory mutant has been shown to cause a defect in adenine nucleotide transport [81], and the nuclear gene responsible for coding the carrier in yeast is currently being cloned for further studies [82]. 

The complete 297 amino acid sequence of the adenine nucleotide transporter has been determined [185] and deductions have been made about the two-dimensional structure in the plane perpendicular to the membrane. Some of these deductions have been made using computer analyses of the amino acid sequence [186], Using a computer program to locate sequence homologies, three domains have been identified within the sequence with significant sequence overlap. The three repeating areas are characterized by a conserved region centered on a cysteine residue found in three... 

Shortzer, H. G-, and Racker, E. (1976). Reconstitution and characterization of the adenine nucleotide transporter derived from bovine heart mitochondria. /. EwJ. Ckem. 251, 2446-2452. 

Revetto MJ (1985) Myocardial nucleotide transport. Annu Rev Physiol 47 605-616... 

SLC2A2, glucose transporter 2 SLC28A1, concentrative nucleotide transporter 1 SLC29A1, equilibrative transporter 1 and SLC15A1, di/tripeptide transporter. 

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