Translocases

Amphomycin inhibits bacterial ceU wall synthesis at the translocase step by binding to the large isoprenoid Hpid called undecaprenylphosphate (173,174). In eukaryotes, in a similar manner, amphomycin binds to the large isoprenoid Hpid called doHcholphosphate thus blocking the transfer of mannose from its uridinediphosphate derivative to this Hpid (173—177). Amphomycin has been patented for use as a feed additive (178). 

A different kind of enzyme, translocase [80700-39-6], which transfers a fragment of NAD to the protein—synthesis factor (elongation factor 2), is catalyzed by diphtheria toxin, thereby inhibiting protein synthesis (43). In tumor cells, the rate of protein synthesis is 100 to 1000 times more sensitive to diphtheria toxin than the analogous process in normal cells (41) therefore, diphtheria toxin is selectively toxic to tumor cells. 

FIGURE 24.9 The formation of acylcar-nitines and their transport across the inner mitochondrial membrane. The process involves the coordinated actions of carnitine acyltrans-ferases on both sides of the membrane and of a translocase that shuttles O-acylcarnitines across the membrane. 

Chaperones. Figure 2 The multiple roles of BiP in the biogenesis of the secretory proteins. BiP, immunoglobulin heavy chain binding protein ER, endoplasmic reticulum ERAD, ER-associated degradation ERj, resident ER protein with J-domain Sec61, core subunit of the protein translocase UPR, unfolded protein response that involves several signal transduction pathways that are activated in order to increase the biosynthetic capacity and decrease the biosynthetic burden of the ER... 

Carnitine (p-hydroxy-y-trimethylammonium butyrate), (CHjljN"—CH2—CH(OH)—CH2—COO , is widely distributed and is particularly abundant in muscle. Long-chain acyl-CoA (or FFA) will not penetrate the inner membrane of mitochondria. However, carnitine palmitoyltransferase-I, present in the outer mitochondrial membrane, converts long-chain acyl-CoA to acylcarnitine, which is able to penetrate the inner membrane and gain access to the P-oxidation system of enzymes (Figure 22-1). Carnitine-acylcar-nitine translocase acts as an inner membrane exchange transporter. Acylcarnitine is transported in, coupled with the transport out of one molecule of carnitine. The acylcarnitine then reacts with CoA, cat-... 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

The transport is accomplished with the participation of carnitine, which takes up the acyl from acyl-CoA on the outer membrane side. Acylcamitine assisted by carnitine translocase diffuses to the inner side of the membrane to give its acyl to the CoA located in the matrix. The process of reversible acyl transfer between CoA and carnitine on the outer and inner sides of the membrane is effected by the enzyme acyl-CoA-camitine transferase. 

Eipi (Wheelock etal., 1991) Eipil (Huang and Komuniecki, 1997) E3BP, E3-binding protein (p45) E3 ER, enoyl CoA reductase (Duran etal. 1993, 1998) AAT, adenine nucleotide translocase a-tubulin. UE, unembryonated egg L1, first-stage larva L2, second-stage larva L3, third-stage larva M, adult muscle ... 

Burger, H. J., Maas, J., Hammerl, R., Schmidt, D., Strohschein, S., Hemmerle, H., Schubert, G., Petry, S., Kramer, W., Prolonged blood glucose reduction in mrp-2 deficient rats (GY/TR(—)) by the glucose-6-phosphate translocase inhibitor S 3025, Biochim. Biophys. Acta 2002,... 

Smith AJ, van Helvoort A, van Meer G, Szabo K, Welker E, Szakacs G et al. MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem 2000 275(31) 23530—23539. 

ADP outside the mitochondria is swapped for ATP inside the mitochondria by a specific translocase. 

An ATP-dependent aminophospholipid translocase activity in plasma membranes prevents this occurrence in healthy cells. 

Van Helvoort, A., Smith, A. J., Sprang, H. et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87 507-17,1996. 

FIGURE 31-7 Mitochondrial carriers. Ions and small molecules enter the intermembrane space, since the outer mitochondrial membrane is not a significant permeability barrier. However, the inner mitochondrial membrane is impermeable to ions except those for which there are specific carriers. Most of the carriers are reversible, as indicated by two-headed arrows. Compounds transported in one direction are indicated in red. The ATP/ADP translocase and the aspartate-glutamate carrier are both electrophoretic their transport is driven in the direction of the mitochondrial membrane potential, as indicated by red arrows. Glutamine is carried into the matrix by an electroneutral carrier. The unimpaired functioning of mitochondrial carriers is essential for normal metabolism. (Adapted with permission from reference [70].)... 

A few patients have been described with a defect involving the carnitine-acylcarnitine translocase system, which facilitates the movement of long-chain acylcarnitine esters across the inner membrane of the mitochondrion (Fig. 42-2). These patients have extremely low carnitine concentrations and minimal dicarboxylic aciduria [4]. 

Defects of mitochondrial transport interfere with the movement of molecules across the inner mitochondrial membrane, which is tightly regulated by specific translocation systems. The carnitine cycle is shown in Figure 42-2 and is responsible for the translocation of acyl-CoA thioesters from the cytosol into the mitochondrial matrix. The carnitine cycle involves four elements the plasma membrane carnitine transporter system, CPT I, the carnitine-acyl carnitine translocase system in the inner mitochondrial membrane and CPT II. Genetic defects have been described for each of these four steps, as discussed previously [4,8,9]. 

There are several hypotheses for a specific mechanism by which ONOO- can control the open state of the PTPC. Briefly the PTPC is regulated by primary constituents of the pore, including the inner membrane adenine nucleotide translocase (ANT) and the outer membrane protein voltage-dependent anion channel (VDAC or porin). The VDAC-ANT complex can bind to signaling proteins that modulate permeability transition, such as pro-apoptotic Bax (which opens the pore) and anti-apoptotic Bcl-2... 

Chaddock, A., Mant, A., Karnauchov, I., Brink, S., Herrmann, R., Klosgen, R., and Robinson, C. (1995). A new type of signal peptide central role of a twin-arginine motif in transfer signals for the ApH-dependent thylakoidal protein translocase. EMBO J. 

Nilsson, I., Whitley, P., and von Heijne, G. (1994). The COOH-terminal ends of internal signal and signal-anchor sequences are positioned differently in the ER translocase. 

Pfanner, N., Craig, E., and Honlinger, A. (1997). Mitochondrial preprotein translocase. Annu. Rev. Cell Biol. Dev. 13, 25-51. 

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