Shuttle, metabolic

Shank RP, Campbell GLeM (1984a) a-Ketoglutarate and malate uptake and metabolism by synaptosomes further evidence for an astrocyte-to-neurons metabolic shuttle. J Neurochem 42 1153-1161. 

Because the mitochondrial membrane is impermeable to ATP/ADP and NAD/NADH, two transport systems are necessary for the function of the R.c. One is the ATP/ADP carrier, which effects facilitated exchange diffusion, and the other is a metabolic shuttle (see Hydrogen metabolism) which allows reducing equivalents generated in the cytoplasm to enter the mitochondrion. 

A substantial fraction of the named enzymes are oxido-reductases, responsible for shuttling electrons along metabolic pathways that reduce carbon dioxide to sugar (in the case of plants), or reduce oxygen to water (in the case of mammals). The oxido-reductases that drive these processes involve a small set of redox active cofactors , that is, small chemical groups that gain or lose electrons. These cofactors include iron porjDhyrins, iron-sulfur clusters and copper complexes as well as organic species that are ET active. 

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. 

C14-0083. Although the ATP-ADP reaction is the principal energy shuttle in metabolic pathways, many other examples of coupled reactions exist. For example, the glutamic acid-glutamine reaction discussed in the text can couple with the acetyl phosphate reaction shown in Example 14-10. Write the balanced equation for the coupled reaction operating in the direction of overall spontaneity and calculate A G ° for the overall process. 

The hemolymphal transport of carotenoids by lipophorin has been elucidated and documented (Law and Wells 1989, Tsuchida et al. 1998, Arrese et al. 2001, Canavoso et al. 2001), as has plasma transport by mammalian lipoproteins (Paker 1996, Yeum and Russell 2002). Lipophorin serves as a shuttle that moves carotenoids from one tissue to another without itself entering the cells, in stark contrast to the vertebrate low-density lipoprotein (LDL) (Brown and Goldstein 1986), which is endocytosed and metabolized in the cell. Here, we focus on the recent biochemical and genetic studies of the intracellular CBP of the silkworm, which mainly transports lutein. We hope this review provides insights into the studies of CBPs in other organisms. 

Long-chain fatty acids can slowly cross the mitochondrial membrane by themselves, but this is too slow to keep up with their metabolism. The carnitine shuttle provides a transport mechanism and allows control of (3 oxidation. Malonyl-CoA, a precursor for fatty acid synthesis, inhibits the carnitine shuttle and slows down (3 oxidation (Fig. 13-5). 

THE MALATE-ASPARTATE SHUTTLE HAS A KEY ROLE IN BRAIN METABOLISM 541... 

The malate-aspartate shuttle has a role in linking metabolic pathways in brain 542... 

Glutamate and glutamine metabolism is compartmentalized in brain 548 A specialized glutamate-glutamine cycle operates in GABAergic neurons and surrounding astrocytes 549 Several shuttles act to transfer nitrogen in brain 549... 

The astrocyte-neuron lactate shuttle hypothesis is controversial. In recent years the possibility that lactate, formed within the brain and released by astrocytes, is an important neuronal substrate both for energy and incorporation into neurotransmitters has been the subject of many studies and considerable controversy. There is evidence that suggests transient release of lactate in human brain on stimulation [48,8,88], Little is known about the highly active metabolism that takes place in the many elaborate, lamellar distal processes of astrocytes dispersed through the neuropil and interacting with an estimated >100,000 synapses [82, and references therein]. However, it is well established that astrocytes do respond to neuronal activity [89], For example, in the isolated mouse optic nerve preparation, upon stimulation, astrocytic glycogen... 

Cheeseman, A. J. and Clark, J. B. Influence of the malate-aspartate shuttle on oxidative metabolism in synaptosomes. /. Neurochem. 50 1559-1565,1988. 

Examples of such intra cellular membrane transport mechanisms include the transfer of pyruvate, the symport (exchange) mechanism of ADP and ATP and the malate-oxaloacetate shuttle, all of which operate across the mitochondrial membranes. Compartmentalization also allows the physical separation of metabolically opposed pathways. For example, in eukaryotes, the synthesis of fatty acids (anabolic) occurs in the cytosol whilst [3 oxidation (catabolic) occurs within the mitochondria. 

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 final reactions to be considered in the metabolism of ethanol in the liver are those involved in reoxidation of cytosolic NADH and in the reduction of NADP. The latter is achieved by the pentose phosphate pathway which has a high capacity in the liver (Chapter 6). The cytosolic NADH is reoxidised mainly by the mitochondrial electron transfer system, which means that substrate shuttles must be used to transport the hydrogen atoms into the mitochondria. The malate/aspartate is the main shuttle involved. Under some conditions, the rate of transfer of hydrogen atoms by the shuttle is less than the rate of NADH generation so that the redox state in the cytosolic compartment of the liver becomes highly reduced and the concentration of NAD severely decreased. This limits the rate of ethanol oxidation by alcohol dehydrogenase. 

The most important process in the degradation of fatty acids is p-oxidation—a metabolic pathway in the mitochondrial matrix (see p. 164). initially, the fatty acids in the cytoplasm are activated by binding to coenzyme A into acyl CoA [3]. Then, with the help of a transport system (the carnitine shuttle [4] see p. 164), the activated fatty acids enter the mitochondrial matrix, where they are broken down into acetyl CoA. The resulting acetyl residues can be oxidized to CO2 in the tricarboxylic acid cycle, producing reduced... 

F. The electrons that are generated from the first step in ethanol metabolism (catalyzed by alcohol dehydrogenase) are transported into the mitochondrion by these two shuttles. 

Carnitine deficiency leads to impaired carnitine shuttle activity the resulting decreased LCFA metabolism and accumulation of LCFAs In tissues and wasting of acyl-carnitine in urine can produce cardiomyopathy, skeletal muscle myopathy, encephalopathy, and impaired liver function. 

Under physiologic conditions, carnitine is primarily required to shuttle long-chain fatty acids across the inner mitochondrial membrane for FAO and products of peroxisomal /1-oxidation to the mitochondria for further metabolism in the citric acid cycle [40, 43]. Acylcarnitines are formed by conjugating acyl-CoA moieties to carnitine, which in the case of activated long-chain fatty acids is accomplished by CPT type I (CPT-I) [8, 44]. The acyl-group of the activated fatty acid (fatty acyl-CoA) is transferred by CPT-I from the sulfur atom of CoA to the hydroxyl group of carnitine (Fig. 3.2.1). Carnitine acylcarnitine translocase (CACT) then transfers the long-chain acylcarnitines across the inner mitochondrial membrane, where CPT-II reverses the action of CPT-I by the formation of acyl-CoA and release of free un-esterified carnitine. 

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