Glycerol-3-phosphate transporter

Auer, M, Kim, M. J., Lemieux, M. J., Villa, A., Song, J., Li, X.-D. and Wang D.-N. (2001). High-yield expression and functional analysis of Escherichia coli glycerol-3-phosphate transporter, Biochemistry, 40, 6628-6635. 

Huang Y, Lemieux MJ, Song J, Auer M, Wang DN. Structure 82. and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 2003 301(5633) 616-620. 

Wang DN. Three-dimensional crystallization of the Escherichia 68. coli glycerol-3-phosphate transporter a member of the major facilitator superfamily. Protein Sci. 2003 12 2748-2756. 

Relatively few membrane transport proteins have been structurally characterized. Some of the best understood examples to date are the lactose permease and glycerol-3-phosphate transporter and the Ca + P-type ATPase (which is a primary ion pump). Other structurally well-characterized transport proteins include the bacterial porins and siderophore receptor proteins. In addition structures have been determined for several ion channels and additional bacterial transporters that are either directly relevant to or models for proteins important in drug transport. The following web sites maintained by Hartmut Michel and Stephen White respectively, contain exceptionally useful listings of these and other solved membrane protein structures and are frequently updated ... 

SLC35 (3) SLC37 (1) CMP-sialic acid and UDP-galactose transporter Glycerol-3-phosphate transporter CST, UGALT Ubiquitous... 

Elvin, C.M., Hardy, C.M. and Rosenberg, H. (1 985) P. exchange mediated by the CIpT-dependent sn-glycerol-3-phosphate transport system in Escherichia coli. Journal of Bacteriology 1 51, 1054-1058. 

The second electron shuttle system, called the malate-aspartate shuttle, is shown in Figure 21.34. Oxaloacetate is reduced in the cytosol, acquiring the electrons of NADH (which is oxidized to NAD ). Malate is transported across the inner membrane, where it is reoxidized by malate dehydrogenase, converting NAD to NADH in the matrix. This mitochondrial NADH readily enters the electron transport chain. The oxaloacetate produced in this reaction cannot cross the inner membrane and must be transaminated to form aspartate, which can be transported across the membrane to the cytosolic side. Transamination in the cytosol recycles aspartate back to oxaloacetate. In contrast to the glycerol phosphate shuttle, the malate-aspartate cycle is reversible, and it operates as shown in Figure 21.34 only if the NADH/NAD ratio in the cytosol is higher than the ratio in the matrix. Because this shuttle produces NADH in the matrix, the full 2.5 ATPs per NADH are recovered. 

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Furthermore, if the antibiotic passes membranes through a specific port of entry, its mutational loss leads to resistance. The lack of the outer membrane protein OprD in P. aeruginosa causes resistance to the (3-lactam antibiotic imipenem. Fosfomycin passes the cytoplasmic membrane via an L-a-glycerol phosphate permease. This transport system is not essential for bacterial growth and therefore mutants with a reduced expression are frequently selected under therapy. 

Electrons from NADH outside the mitochondria are transported into the mitochondria by the malate-aspartate shuttle or the a-glycerol phosphate shuttle. 

Rotenone inhibits the transfer of electrons from NADH into the electron transport chain. The oxidation of substrates that generate NADH is, therefore, blocked. However, substrates that are oxidized to generate FADH2 (such as succinate or a-glycerol phosphate) can still be oxidized and still generate ATP. Because NADH oxidation is blocked, the NADH pool becomes more reduced in the presence of rotenone since there s nowhere to transfer the electrons. 

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

B. The calculated ATP yield is somewhat variable because glycolytic electrons transferred by the glycerol phosphate shuttle bypass complex I of the electron transport chain. 

Glucose transport into cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport... 

Figure 18-5 A current concept of the electron transport chain of mitochondria. Complexes I, III, and IV pass electrons from NADH or NADPH to 02, one NADH or two electrons reducing one O to HzO. This electron transport is coupled to the transfer of about 12 H+ from the mitochondrial matrix to the intermembrane space. These protons flow back into the matrix through ATP synthase (V), four H+ driving the synthesis of one ATP. Succinate, fatty acyl-CoA molecules, and other substrates are oxidized via complex II and similar complexes that reduce ubiquinone Q, the reduced form QH2 carrying electrons to complex III. In some tissues of some organisms, glycerol phosphate is dehydrogenated by a complex that is accessible from the intermembrane space.

The lipid-soluble ubiquinone (Q) is present in both bacterial and mitochondrial membranes in relatively large amounts compared to other electron carriers (Table 18-2). It seems to be located at a point of convergence of the NADH, succinate, glycerol phosphate, and choline branches of the electron transport chain. Ubiquinone plays a role somewhat like that of NADH, which carries electrons between dehydrogenases in the cytoplasm and from soluble dehydrogenases in the aqueous mitochondrial matrix to flavoproteins embedded in the membrane. Ubiquinone transfers electrons plus protons between proteins within the... 

Figure 18-18 (A) The glycerol-phosphate shuttle and (B) the malate-aspartate shuttle for transport from cytoplasmic NADH into mitochondria. The heavy arrows trace the pathway of the electrons (as 2H) transported.

Mitochondria employ a host of carriers, or transporters, to move molecules across the inner mitochondrial membrane. The electrons of cytoplasmic NADH are transferred into the mitochondria by the glycerol phosphate shuttle to form FADH2 from FAD. The entry of ADP into the mitochondrial matrix is coupled to the exit of ATP by ATP-ADP translocase, a transporter driven by membrane potential. 

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