Mitochondrial metabolism properties

Most of the studies on the intracellular distribution of metabolites across the mitochondrial membrane have been carried out with perfused liver (method 1) or isolated hepatocytes (methods 2 and 3), mainly because the metabolic properties of these preparations had been well characterised in the past. It is important that, in general, all fractionation methods give comparable values for the anion distribution across the mitochondrial membrane under comparable conditions although they differ in detail [34],... 

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

The oxidation of acetaldehyde to acetic acid has been studied with NAD-linked ALDH purified from human, rat and Syrian hamster liver (Klyosov et al., 1996). The mitochondrial enzymes from these species have very similar kinetic properties, whereas human cytosolic ALDHl has a value of about 180 pM, compared with 15 pM and 12 pM for rats and hamsters, respectively. Apparently, in human liver, only mitochondrial ALDH oxidizes acetaldehyde at physiological concentrations, whereas both mitochondrial and cytosolic ALDHs of rodents can participate in acetaldehyde metabolism. The rodent cytosolic ALDHs are at least 10 times more sensitive that the human enzyme to inhibition by disulfiram. 

In summary, the total quantity of mitochondrial membrane surface area and the per unit area flux of protons through futile cycle channels are higher in mammals than in reptiles of similar body size. These differences in the quantitative and qualitative properties of mitochondria seem capable of accounting for much of the difference in mass-specific metabolic rate between mammals and reptiles that is, they may provide a mechanistic account for the observed four- to fivefold difference in the a term in the allometric equation, M = aW0 75. 

The metabolic pathways leading to the production of these urinary pyridinium metabolites are likely to be mediated by one or more forms of liver cytochrome P450. In vitro metabolic studies with rodent (Igarashi et al., unpublished results) and human (Usuki et al., submitted) microsomal preparations have demonstrated the NADPH-dependent oxidation of both HP and HPTP to HPP. Ongoing studies in the authors laboratory have shown that HPP and related pyridinium metabolites are present in brain tissues obtained from C57 black mice that had been treated with HPTP (Van der Schyf et al. 1994). Additionally, results obtained from intra-cerebral microdialysis, mitochondrial respiration, and rat embryonic mesencephalic cell culture studies suggest that HPP possesses MPP type neurotoxic properties (Rollema et al. 1992, 1994 Bloomquist et al. 1994). 

Liibben M, Kolmerer B, Saraste M (1992) On archaebacterial terminal oxidase combines core structures of two mitochondrial respiratory complexes. EMBO J 11 805-812 Lundgren DG, Silver M (1980) Ore leaching by bacteria. Annu Rev Microbiol 34 263-283 Lyric RM, Suzuki I (1970a) Enzyme involved in the metabolism of thiosulfate by Thiobacillus thioparus III. Properties of thiosulfate-oxidizing enzyme and proposed pathway of thiosulfate oxidation. Can J Biochem 48 355-363... 

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