Mitochondrial metabolism

Diaz, F. and Komuniecki, R.W. (1996) Characterization of the alpha-ketoglutarate dehydrogenase complex from Fasciola hepatica potential implications for the role of calcium in the regulation of helminth mitochondrial metabolism. Molecular and Biochemical Parasitology 81,243—246. 

Ni et al. [144] also investigated the profiles of major metabolites of primaquine produced from liver microsomal and mitochondrial metabolism, in vitro by silica gel thin-layer and reversed-phase high performance liquid chromatography. The results... 

Diseases of Carbohydrate, Fatty Acid and Mitochondrial Metabolism... 

The biochemical classification of mitochondrial DNA is based on the five major steps of mitochondrial metabolism 708... 

Defects of nuclear DNA also cause mitochondrial diseases. As mentioned above, the vast majority of mitochondrial proteins are encoded by nDNA, synthesized in the cytoplasm and imported into the mitochondria through a complex series of steps. Diseases can be due to mutations in genes encoding respiratory chain subunits, ancillary proteins controlling the proper assembly of the respiratory chain complexes, proteins controlling the importation machinery, or proteins controlling the lipid composition of the inner membrane. All these disorders will be transmitted by mendelian inheritance. From a biochemical point of view, all areas of mitochondrial metabolism can be affected (see below). 

The biochemical classification of mitochondrial DNA is based on the five major steps of mitochondrial metabolism. These steps are illustrated in Figure 42-3 and divide mitochondrial diseases into five groups defects of mitochondrial transport, defects of substrate utilization, defects of the Krebs cycle, defects of the respiratory chain and defects of oxidation-phosphorylation coupling. 

K Yugi and M. Tomita, Applications note A general computational model of mitochondrial metabolism in a whole organelle scale. Bioinformatics 20(11), 1795 1796 (2004). 

There are at least three ways in which mitochondrial ATP generation can be impaired mutations in mitochondrial DNA, mutations in nuclear DNA and effects of toxic compounds. The reactions in mitochondrial metabolism that are affected by some toxic compounds are described in Appendix 9.12. 

Mitochondria are surrounded by an inner and an outer membrane (see p. 210). The outer membrane contains porins, which allow smaller molecules up to 10 kDa in size to pass. By contrast, the inner membrane is also impermeable to small molecules (with the exception of water and the gases O2, CO2, and NH3). All of the other substrates of mitochondrial metabolism, as well as its products, therefore have to be moved through the inner membrane with the help of special transporters. 

Hexachlorobutadiene and its metabolites preferentially distribute to the kidney, liver, adipose deposits, and possibly the brain. Some hexachlorobutadiene metabolites inhibit mitochondrial metabolism and react with DMA, resulting in cell death or tumorigenesis. Hexachlorobutadiene metabolites are excreted in the urine and feces. There is limited degradation to carbon dioxide which is exhaled from the lungs. 

Monensin, (X), obtained from streptomyces cinnamonensis, is an inhibitor of mitochondrial metabolism. As isolated, it is a mixture of... 

D. E. Befroy, K. Petersen, D. L. Rothman and G. I. Shulman, Assessment of in vivo mitochondrial metabolism by magnetic resonance spectroscopy. Methods Enzymol., 2009,457,373-393. 

Gabaldon T, Huynen MA (2003) Reconstruction of the proto-mitochondrial metabolism. Science 301 609... 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

Coomes, M.W. Prough, R.A. (1983) The mitochondrial metabolism of 1,2-disubstituted hydrazines, procarbazine and 1,2-dimethylhydrazine. DrugMetab. Disp., 11, 550-555... 

Figure 24-11 Integration of the urea cycle with mitochondrial metabolism. Green lines trace the flow of nitrogen into urea upon deamination of amino acids or upon removal of nitrogen from the side chain of glutamine.

Ascorbic acid synergist in cold survival Niacin synergist in mitochondrial metabolism... 

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