Metabolism in mitochondria

When cyanide blocks oxidative metabolism in mitochondria, cells shift their metabolism and enhanced glucose utilization occurs. One consequence of this altered metabolic pattern is accumulation of nicotinamide adenine dinucleotide (NADH). NADH is a powerful stimulant of calcium mobilization from cell stores through "inositol triphosphate receptors." Elevated calcium damages cells. Increase in cellular NADH, therefore, is an important event in the toxic action of cyanide (Kaplin et al. 1996). 

Brand, M.D. (1995). Control analysis of energy metabolism in mitochondria. Biochem. Soc. Trans. 23 371-376. 

It is not improbable that further investigation of PolyP metabolism in mitochondria and chloroplasts would reveal novel features of similarity with eubacteria in favour of the endosymbiotic theory of the origin of eukaryotes. 

After comparing the protein profiles of myocardial mitochondria between a chronic restraint stress group and a control group, 11 protein spots were found to change, of which seven were identified. Five of these proteins, carnitine palmitoyltransferase 2, mitochondrial acyl-CoA thioesterase 1, isocitrate dehydrogenase 3 (NAD ) alpha, fumarate hydratase 1, and pyruvate dehydrogenase beta, were foimd to decrease in abimdance following chronic restraint stress with fimctional roles in the Krebs cycle and lipid metabolism in mitochondria. The other two proteins, creatine kinase and prohibitin, increased after chronic restraint stress (liu et ak, 2004). 

Malate, produced in the cytostol, enters the mitochondria where it undergoes dismutation [28]. One half of the malate is oxidized and decarboxylated to pyruvate by malic enzyme (ME) [29,30], while the other half undergoes dehydration to form fumarate which is reduced to succinate through an electron-transport-associated fu-marate-reductase (FR) [31-33]. Metabolism of both the halves of malate produces one mole of NADH each. From pyruvate and succinate, the metabolism proceeds through the sequence of reactions as described by Komuniecki et al. [34]. During the entire metabolism in mitochondria, ATP is produced at various steps either by substrate level phosphorylation or by anaerobic phosphorylation at site 1 [28,30,35,36]... 

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

Fig. 3. Oxidative metabolism in mitochondria. The inner mitochondrial membrane forms infoldings, called cristae, which enclose the mitochondrial matrix. Most of the enzymes for the TCA cycle, the P-oxidation of fatty acids, and for mitochondrial DNA synthesis are found in the matrix. ATP synthase and the protein complexes of the electron transport chain are embedded in the inner mitochondrial membrane. The outer mitochondrial membrane is permeable to small ions, but the inner mitochondrial membrane is impermeable.

In the fully oxygenated postprandial state in hepatocytes, pyruvate takes the mitochondrial route. The stimulation by insulin of the pyruvate dehydrogenase complex (Sec. 11.7), via dephosphorylation mediated by pymvate dehydrogenase phosphatase, opens up the pathway to pymvate metabolism in mitochondria. 

Garber, A. J., and Ballard, F. J., 1970, Regulation of P-enolpyruvate metabolism in mitochondria from guinea pig liver, J. Biol. Chem. 245 2229. 

A summary of the sequential reactions of the -oxidation cycle and the relationship of the overall process to energy metabolism in mitochondria is shown in Figure 3.20. Two carbon units (as acetyl-CoA) are removed from the fatty acyl-Co A substrate by the successive action of four enzymes - acyl-CoA dehydrogenase, enoyl hydratase, a second dehydrogenase and a thiolase. These enzymes are detailed in Table 3.12. 

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