Mitochondrial oxidation changes

Note The.se P/O ratios of 2.5 and 1.5 for mitochondrial oxidation of NADH and [FADHg] are consen.sns values. Because diey may not reflect actual values and because these ratios may change depending on metabolic conditions, the.se estimates of ATP yield from glucose oxidation are approximate. 

The mechanism for the production of O2" in ischaemic tissue appears to involve changes in purine metabolism within ischaemic cells. Sublethal hypoxia decelerates mitochondrial oxidative phosphorylation, rendering the production of ATP dependent upon the... 

Surface fluorescence of NADH/NADPH can be recorded continuously with a DC fluorimeter and correlated with changes in experimental conditions. A mercury arc lamp (with a 340-375 nm filter in front) is used as a hght source for fluorescence excitation. The fluorescence response of reduced NADH/NADPH was measured at 450-510 nm. The DC fluorimeter and the Hg arc lamp are connected to the kidney by a trifurcated fiber optics light guide. NADH/NADPH fluorescence emission can be corrected for changes in tissue opacity by a 1 1 subtraction of reflectance changes at 340-375 nm from the fluorescence. To determine NADH/NADPH redox state of the total surface area of kidney cortex and to evaluate whether certain areas were insufficiently perfused, fluorescence photographs of the total surface area were taken. The study demonstrated that the surface fluorescence method is simple and provides specific information about the mitochondrial oxidation-reduction state. 

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

Certain foreign compounds can cause changes in body temperature, which may become a toxic response if they are extreme. Substances such as 2,4-dinitrophenol and salicylic acid will raise body temperature, as they uncouple mitochondrial oxidative phosphorylation. Thus, the energy normally directed into ATP during oxidative phosphorylation is released as heat. Substances that cause vasodilation may cause a decrease in body temperature. 

P4. Papa, S., Mitochondrial oxidative phosphorylation changes in the hfe span. Molecular aspects and physiopathological implications. Biochim. Biophys. Acta 1276, 87-105 (1996). 

Vitamin E deficiency is also associated with impaired mitochondrial oxidative metabolism and impaired activity of microsomal cytochrome P450-dependent mixed-function oxidases, and hence the metabolism of xenobi-ofics. There is no evidence that vitamin E has any specific role in electron transport in mitochondria or microsomes. Again, changes in membrane lipids and oxidative damage presumably account for the observed metabolic abnormalities. 

Spectral Analysis. - A new method of analysis of ATP utilisation and resynthesis has been developed which simulates cellular ATP flux, mitochondrial oxidative phosphorylation and creatine kinase kinetics. The model was used to examine previously published P NMR data of changes in PCr and Pi in resting muscle, muscle exercising during ischaemia and muscle in aerobic recovery. The model allowed estimation of the maximal velocity of oxidative... 

Much evidence, nevertheless, shows that the acceleration of hepatic fatty acid oxidation under ketogenic conditions entails important intracellular adaptive changes at steps subsequent to fatty acid activation. A set of these adaptations enhance the proportion of extramitochondrial fatty acyl-CoA being directed to the mitochondrial oxidative route over that being channeled for triacylglycerol and lipoprotein synthesis. Opposite changes in the... 

Both ischaemia (clamping of the superior mesenteric artery for 30,60, 90 min) and ischaemia/reperfusion affected respiratory function of isolated rat enterocyte mitochondria as compared to control (Madesh et al. 2000). Preconditioning with nitric oxide donor, sodium nitroprusside (1 mM, given into the proximal jejunal lumen at a rate of 1 ml/ min), significantly enhanced the recovery of the respiratory control rate. Mitochondrial lipid changes suggestive of activation of phospholipase... 

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