Affecting aerobic metabolism

TOXICATsTTS AFFECTING AEROBIC METABOLISM. The high energy demands of the heart make it susceptible to toxicants that interfere with oxy n availability, carbohydrate metabolism, or oxidative phosphorylation. 

Answer B, Inheritance only from affected females strongly suggests a defect in a mitochondrial gene. Defects in mitochondrial gene expression phenotypkaUy present as problems in nerves and/or muscles, tissues with high aerobic metabolism. 

Hypoxia is a deficiency of oxygen needed to maintain cellular homeostasis. It may be caused by a reduction in blood supply, namely ischemia, decreased cardiopulmonary function, and diminished oxygen-carrying capacity of the blood. Subsequent oxygen deficiency in tissues leads to depressed aerobic metabolism and, thus, insufficient ATP synthesis. Reductions in blood flow also exacerbate oxygen deprivation by impairing delivery of nutrients, such as glucose, and the removal of metabolic wastes, such as C02, from affected cells. 

Exercise performance seems to be greatly affected by the chronic level of physical activity experienced by the animal or Individual. For example, differences In the capacity for prolonged exercise seem obvious between wild and domesticated animals. This Is probably due. In part, to Inherent biochemical differences between the muscles of active and less active species ( 1 ). Muscles of wild animals appear darker than those of their domesticated counterparts ( ). Further, variations In activity patterns due to seasonal change (3 ) or hibernation ( ), are associated with differences In the enzymes related to oxidative metabolism. Thus, In a general sense physical activity seems to be associated with biochemical changes that enhance the muscle s capacity for aerobic metabolism. 

However, as distinguished from the aerobic metabolism of normal cells, cancer cell metabolism is in the main anaerobic and does not invoke the carboxylic acid cycle, dependent on oxygen and fimdamental to cell respiration, as set forth in Chapter 3 for glycolysis. Thus, respiration of the cancerous cell is excluded from consideration. Hence, from this standpoint, the anticancer claims for amygdalin or laetrile can be viewed as missing the mark. That is, under this interpretation, cyanide would affect aerobic normal cells but not anaerobic cancerous cells. 

Similarly, if one compares the form of the enzyme lactate dehydrogenase found in heart muscle to the type found in skeletal muscle, one can see small differences in amino acid composition. These differences in turn affect the reaction catalyzed by this enzyme, the conversion of pyruvate to lactate. The heart type has a high Kf, or a low afiinity for pyruvate, and the muscle type has a low K, or a high afiinily for pyruvate. This means that the pyruvate win be preferentially converted to lactate in the muscle but will be preferentially used for aerobic metabolism in the heart, rather than being converted to lactate. These conclusions are consistent with the known biology and metabolism of these two tissues. 

The energy utilization by the cardiac muscle is a complex process which is strongly affected by metabolic and mechanical parameters. The cardiac muscle derives almost all of its energy supply by aerobic metabolism and is thus highly dependent on the oxygen supply. Short cessations of the oxygen supply to the contracting tissues will affect the contraction mechanics within a few seconds. 

In addition to the well-known iron effects on peroxidative processes, there are also other mechanisms of iron-initiated free radical damage, one of them, the effect of iron ions on calcium metabolism. It has been shown that an increase in free cytosolic calcium may affect cellular redox balance. Stoyanovsky and Cederbaum [174] showed that in the presence of NADPH or ascorbic acid iron ions induced calcium release from liver microsomes. Calcium release occurred only under aerobic conditions and was inhibited by antioxidants Trolox C, glutathione, and ascorbate. It was suggested that the activation of calcium releasing channels by the redox cycling of iron ions may be an important factor in the stimulation of various hepatic disorders in humans with iron overload. 

Redox reactions in soils are affected by a number of parameters, including temperature, pH (see Chapter 7), and microbes. Microbes catalyze many redox reactions in soils and use a variety of compounds as electron acceptors or electron donors. For example, aerobic heterotrophic soil bacteria may metabolize readily available organic carbon using NO3, NOj, N20, Mn-oxides, Fe-oxides and compounds such as arsenate (As04 ) and selenate (Se04 ) as electron acceptors. Similarly, microbes may use reduced compounds or ions as electron donors, for example, NH4, Mn2+, Fe2+, arsenite (AsCXj), and selenite (SeO ). 

The colon contains both aerobic and anaerobic micro-organisms that may metabolize some drugs. Crohn s disease affects the colon and thickens the bowel wall. The microflora may also become more anaerobic. Absorption of clindamycin and propranolol are increased, whereas other drugs have reduced absorption with this disease (Rubinstein et al., 1988)... 

---