Metabolite shuttles

The fact that mitochondria are present means that these cells can convert cytoplasmic NADH into NAD+. The H s, or reducing equivalents, are transported into the mitochondria via metabolite shuttles. 

In the glycerophosphate shuttle, two different glycerophosphate dehydrogenases, one in the cytoplasm and one on the outer face of the mitochondrial inner membrane, work together to carry electrons into the mitochondrial matrix (Figure 21.32). NADH produced in the cytosol transfers its electrons to dihydroxyaeetone phosphate, thus reducing it to glyeerol-3-phosphate. This metabolite is reoxidized by the FAD -dependent mitochondrial membrane enzyme to... 

Cells require a constant supply of N/ X)PH for reductive reactions vital to biosynthetic purposes. Much of this requirement is met by a glucose-based metabolic sequence variously called the pentose phosphate pathway, the hexose monophosphate shunt, or the phosphogluconate pathway. In addition to providing N/VDPH for biosynthetic processes, this pathway produces ribos 5-phosphate, which is essential for nucleic acid synthesis. Several metabolites of the pentose phosphate pathway can also be shuttled into glycolysis. 

Microbial biofuel cells were the earliest biofuel cell technology to be developed, as an alternative to conventional fuel cell technology. The concept and performance of several microbial biofuel cells have been summarized in recent review chapters." The most fuel-efficient way of utilizing complex fuels, such as carbohydrates, is by using microbial biofuel cells where the oxidation process involves a cascade of enzyme-catalyzed reactions. The two classical methods of operating the microbial fuel cells are (1) utilization of the electroactive metabolite produced by the fermentation of the fuel substrate " and (2) use of redox mediators to shuttle electrons from the metabolic pathway of the microorganism to the electrodes. ... 

The concentration of phosphocreatine is usually greater than that of ATP and that of creatine greater than that of ADP so that these metabolites diffuse more rapidly. This is because diffusion depends upon the concentrations of participants and the concentration gradient the larger the gradient, the greater is the rate of diffusion. Consequently, the shuttle is important in cells where the distance between the sites of ATP utilisation and the mitochondria is large... 

Interestingly, this lactate shuttling is not the only important metabolite exchange between these two cell types they also exchange glutamate and glutamine. Glutamate in small quantities is released at neuronal synapses as an... 

Thus, electrons can be directly transferred (DET) to the anode via the cell membrane (a) or via so-called nanowires (b) [vi.vii]. Alternatively, mediated electron transfer (MET) can take place via bacterial electron-shuttling compounds [viii] or reduced secondary metabolites like, e.g., hydrogen, formate, or ethanol [v,ix]. 

It follows from Equation (9.29) that the product Lc remains constant and defines a number of conserved pools of metabolic concentrations. For example, if we were to consider the glycolytic series as an isolated system, with no net flux of phosphate-containing metabolites into or out of the system, then as phosphate is shuttled... 

Fig. 2. The C4 cycle of COj fixation in photosynthesis. The pathway shown is that occurring in Type-1 C4 plants such as Zea mays. Abbreviations RuBP, ribulose 1,5-bisphosphate PGA, 3-phosphogly-cerate PEP, phosphoeno/pyruvate OAA, oxaloacetate. The partial triose-P/PGA shuttle is based primarily on evidence demonstrating concentration gradients that would support metabolite flux between the two cell types.

VDAC plays a role in the regulated flux of metabolites—usually anionic species such as phosphate, chloride, organic anions, and the adenine nucleotides—across the outer membrane. VDAC appears to form an open p -barrel structure similar to that of the bacterial porins (Section 12.5.2). although mitochondrial porins and bacterial porins may have evolved independently. Some cytoplasmic kinases bind to VDAC, thereby obtaining preferential access to the exported ATP. In contrast, the inner membrane is intrinsically impermeable to nearly all ions and polar molecules. A large family of transporters shuttles metabolites such as ATP, pyruvate, and citrate across the inner mitochondrial membrane. The two faces of this membrane will be referred to as the matrix side and the cytosolic side (the latter because it is freely accessible to most small molecules in the cytosol). They are also called the N and P sides, respectively, because the membrane potential is negative on the matrix side and positive on the cytosolic side. 

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. 

A FIGURE 8-7 Summary of the aerobic oxidation of pyruvate and fatty acids in mitochondria. The outer membrane is freely permeable to all metabolites, but specific transport proteins (colored ovals) in the inner membrane are required to import pyruvate (yellow), ADP (green), and P (purple) into the matrix and to export ATP (green). NADH generated in the cytosol is not transported directly to the matrix because the inner membrane is impermeable to NAD and NADH instead, a shuttle system (red) transports electrons from cytosolic NADH to NAD in the matrix. O2 diffuses into the matrix and CO2 diffuses out. Stage 1 Fatty acyl groups are transferred from fatty acyl CoA and transported across the inner membrane via a special carrier (blue oval) and then reattached to CoA on the matrix side. 

The noncompartmented model consisted of 73 transformers (reaction rates and transport step), balancing 53 metaboHtes. The compartmented approach was buUt on 95 transformers and 75 metabolites. While most of the simulated fluxes were similar in both approaches, a fraction of approximately 15% of totally available ATP was missing in the compartmented model compared to the noncompartmented approach. This was due to the assumed activity of the citrate-pyruvate shuttle that imports pyruvate (via pyruvate/H+ symporter) into mitochondria by exporting citrate (via citrate/malate antiporter). In cytoplasm, citrate is further... 

N. is deactivated by O-methylation a monoamine oxidase then removes the NHj group to produce 3-methoxy-4-hydroxymandelic acid (vanillylmandelic parasympathetic nervous function, and is used for the diagnosis of tumors which produce N. or adrenalin. See ascorbate shuttle. 

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