Mitochondria distribution

A number of water-soluble polymers will cause phase separation when present together at concentrations of a few percent. The most widely used polymers are polyethylene glycol (PEG) and dextran. Proteins, other macromolecules, and cell components such as mitochondria distribute in the phases or collect at the interface. Proteins are destabilized at organic solvent/water interfaces, but when each solvent is water, the interfacial tension is negligible. Some salts such as potassium phosphate will also induce phase separation when a polymer is present, but the salt concentration must be high. Two-phase aqueous systems provide a mild method for purification of proteins, and scale-up to large volumes presents no engineering problems. The polymers... 

Fig. 3. Distribution ofvarious membrane markers (ER, tonoplast, Golgi complex, and mitochondrion) in the fractions of linear sucrose density gradient fractionation of mulberry cortical parenchyma cells in February.

Given their ubiquitous distribution, the PRAT Tims may have had an early origin during the conversion of the proto-mitochondrion. However, these putative translocases have yet to be localized, and no phylogenetic analyses have been generated to assess their affinities. 

FIGURE 19-1 Biochemical anatomy of a mitochondrion. The convolutions (cristae) of the inner membrane provide a very large surface area. The inner membrane of a single liver mitochondrion may have more than 10,000 sets of electron-transfer systems (respiratory chains) and ATP synthase molecules, distributed over the membrane surface. Heart mitochondria, which have more profuse cristae and thus a much larger area of inner membrane, contain more than three times as many sets of electron-transfer systems as liver mitochondria. The mitochondrial pool of coenzymes and intermediates is functionally separate from the cytosolic pool. The mitochondria of invertebrates, plants, and microbial eukaryotes are similar to those shown here, but with much variation in size, shape, and degree of convolution of the inner membrane. 

The title of this book means that our inquiry about metabolism must be limited to the actual energy conversion process itself, and it has been widely agreed that this occurs at the mitochondrion in each of the cells of the organism. It is also agreed that the distribution of energy (the currency in respect to wealth) is done by ATP, which yields energy locally when needed. 

Fig. 10.2. The phylogenetic distribution of mitochondrion-related organelles in eukaryotes. Organelle function is indicated as Hhydrogenosome, M mitosome or unknown...

At the present time there is not much data which can be used to describe special properties of m-MDH related to its presence in the mitochondrion. Studies on the distribution of various enzymes inside the organelle indicate that m-MDH is one example of an intermediate class... 

In mammalian tissues, heme bios)mthesis proceeds in eight discrete enzyme-catalysed steps (Figure 2.6). These steps are distributed between two parts of the cell, the mitochondrion, where the major metabolic reactions take place, and the cytosol, which is simply the aqueous phase of the cytoplasm. The first step on the path is the condensation of an intermediate from the citric acid cycle, succinyl coenzyme A (CoA), with the simplest amino acid of aU, glycine. 

Cytoehrome function is inseparable from that of mitochondria, and the inheritance of the cytochrome patterns of the petite and poky (see below) mutants has long been known to follow the 4 0 distribution of maternal or cytoplasmic inheritance, as opposed to the 2 2 distribution of chromosomal genes. That the biochemical machinery for cytoplasmic inheritance exists has been shown by the finding of the necessary genetic and protein-synthesizing components in the mitochondrion (for references, see [42,45,46]). It appears likely that the amount of intrinsically synthesized protein, although indispensable, is small compared to extrinsically produced material. 

Fio. 31. Distribution of the enzymes of heme biosyntbesis in the cell and hypothesis on the lesions in porphyria. If in acute porphyria S-AL-synthetase activity is enhanced as in chemical porphyria rather than that the Shemin cycle is blocked at (1) or the mitochondrion becomes permeable at (1) then i-AL will leak out, some will be converted to PBG, and both will be excreted. In congenital porphyria the PBG isomerase enzyme at (2) is decreased or damaged so UROGEN-I is formed and is in part transformed to COPROGEN-I, which are both excreted. 

Fatty acids are oxidized only in the form of fatty a< l-CoA derivatives, and mitochondria from mammalian tissues contain the full equipment of enzymes necessary for the synthesis and the degradation of fatty acyl-CoA. The enzymes involved in the oxidative process are located in the mitochondrial matrix, and the inner mitochondrial membrane sequesters the oxidative process from the rest of these organelles. On the contrary, the fatty acids activating enzymes (thiokinase) seem to be present in different compartments of the mitochondrion and widely distributed among the subcellular fractions. The significance of this may lie in the fact that the conditions required for fatty acyl-CoA oxidation differ from those required for other CoA—SH dependent pathways. 

Most ATP-requiring reactions occur in the cytosol and produce ADP and orthophosphate. Since most ATP is formed by mitochondrial oxidative phosphorylation (in appropriate cells) from ADP and orthophosphate, these molecules must traverse the inner membrane. ATP and ADP are translocated by the specific adenine-nucleotide-transport system. This antiport system is widely distributed in the membrane and exchanges one mitochondrial ATP for one cytoplasmic ADP. The carrier selectively binds and transports ADP inwards and ATP outwards. The phosphate enters the mitochondrion via a different antiport system, the phosphate carrier, which exchanges it for a hydroxyl ion. 

Unlike glycolysis, which occurs strictly in the cell cytosol, gluconeogen-esis involves a complex interaction between the mitochondrion and the cytosol. This interaction is necessitated by the irreversibility of the pyruvate kinase reaction, by the relative impermeability of the inner mitochondrial membrane to oxaloacetate, and by the specific mitochondrial location of pyruvate carboxylase. Compartmentation within the cell has led to the distribution of a number of enzymes (aspartate and alanine aminotransferases, and NAD -malate dehydrogenase) in both the mitochondria and the cytosol. In the classical situation represented by the rat, mouse, or hamster hepatocyte, the indirect "translocation" of oxaloacetate—the product of the pyruvate carboxylase reaction—into the cytosol is effected by the concerted action of these enzymes. Within the mitochondria oxaloacetate is converted either to malate or aspartate, or both. Following the exit of these metabolites from the mitochondria, oxaloacetate is regenerated by essentially similar reactions in the cytosol and is subsequently decarboxylated to P-enolpyruvate by P-enol-pyruvate carboxykinase. Thus the presence of a membrane barrier to oxaloacetate leads to the functioning of the malate-aspartate shuttle as an important element in gluconeogenesis. 

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