Mitochondria enzyme distribution

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. 

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. 

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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