Mammals metabolism

Far less is known about excretion by terrestrial insects than by terrestrial mammals. Metabolism can take place in the midgut and fat body. Excretion can occur via the malpighian tubules. 

Klopman, G. and Tu, M. (1999) META. A program for the prediction of the products of mammal metabolism of xenobiotics. Blackwell Science, Oxford, UK. 

C. Allantoin is the end product of purine metabolism, and is excreted in the urine of most mammals, exceptions being man and the anthropoid apes. 

A substantial fraction of the named enzymes are oxido-reductases, responsible for shuttling electrons along metabolic pathways that reduce carbon dioxide to sugar (in the case of plants), or reduce oxygen to water (in the case of mammals). The oxido-reductases that drive these processes involve a small set of redox active cofactors , that is, small chemical groups that gain or lose electrons. These cofactors include iron porjDhyrins, iron-sulfur clusters and copper complexes as well as organic species that are ET active. 

Environmental. In general, chlorinated paraffins biodegrade the rate is determined by chlorine content and carbon chain length. Microorganisms previously acclimatized to specific chlorinated paraffins show a greater ability to degrade the compounds than nonacclimatized organisms. Mammals and fish have been shown to metabolize chlorinated paraffins (8). 

In addition to reproductive effects, fish exposed to endocrine disrupters may have a decreased response to stress or decreased growth and metabolism which can affect their ability to survive, or to defend themselves against predators. All of these factors can affect the ability of the species to survive and to reproduce itself in sufficient numbers to maintain the stocks on which our commercial and sport fisheries are based. Not all fish species will be equally susceptible to the effects of endocrine disrupters. Selective sensitivity to such effects, especially those affecting reproduction, may well lead to major changes in the flora and fauna of some of our major aquatic ecosystems as the balance between fish, mammals, invertebrates and plants, and between predators and prey, is destabilised... 

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

Rolfe, D. F., and Brown, G. C., 1997. Cellular energy utilization and molecular oriffin of standard metabolic rate in mammals. Physiological Reviews 77 731-758. 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

Dihydropteroic acid (85) is an intermediate to the formation of the folic acid necessary for intermediary metabolism in both bacteria and man. In bacteria this intermediate is produced by enzymatic condensation of the pteridine, 86, with para-amino-benzoic acid (87). It has been shown convincingly that sulfanilamide and its various derivatives act as a false substrate in place of the enzymatic reaction that is, the sulfonamide blocks the reaction by occupying the site intended for the benzoic acid. The lack of folic acid then results in the death of the microorganism. Mammals, on the other hand, cannot synthesize folic acid instead, this compound must be ingested preformed in the form of a vitamin. Inhibition of the reaction to form folic acid Ls thus without effect on these higher organisms. 

Animal nutritionists have developed formulas to guide them in recommending the amount of food to feed animals in captive situations such as in zoos. First, the number of calorics needed to maintain the animal while at rest is determined—this is called the basal metabolic rate (BMR). In general, a reptile s BMR is only 15 percent that of a placental mammal, while a bird s is quite a bit higher than both a reptile s and a mammal s. For all animals, the number of calories they should receive on a maintenance diet is twice that used at the basal metabolic rate. A growing animal should receive three times the number of calories at the BMR, while an animal in the reproductive phase should receive four to six times the BMR. 

Nonetheless, birds have higher metabolic rates than mammals of similar size. Most small mammals reduce energy costs by seeking protected environments birds spend much of their time exposed. Also, because fat is heavy, the need to fly restricts a bird s ability to store energy. Even with a high-protein diet, a bird must eat as much as 3(1 percent of its body... 

Alcohol sulfates are easily metabolized by mammals and fishes either by oral or intraperitoneal and intravenous administration. Several labeled 35S and 14C alcohol sulfates have been used to determine their metabolism in experiments with rats [336-340], dogs [339], swines [341], goldfish [342], and humans [339]. From all of these studies it can be concluded that alcohol sulfates are absorbed in the intestine of mammals and readily metabolized by to and p oxidation of the alkyl chain and excreted in the urine and feces, but are also partially exhaled as carbon dioxide. Fishes absorb alcohol sulfates through their gills and metabolize them in a similar way to that of mammals. 

Copper is essential in animal metabolism. In some animals, such as the octopus and certain arthropods, it transports oxygen through the blood, a role performed by iron in mammals. As a result, the blood of these animals is green rather than red. In mammals, copper-bearing enzymes are necessary for healthy nerves and connective tissue. 

In view of the increasing number of industrial applications of organ-otins, which are described in the next section, a knowledge of their metabolic fate in mammals is obviously of considerable importance. 

There are very limited data on the kinetics and metabolism of organotins in laboratory mammals. A widespread distribution of organotins throughout body tissues has been observed. Transplacental transfer seems to occur, whereas transfer across the blood-brain barrier is limited, since brain levels are usually low. The only compound for which data are available on metabolites is dibutyltin, which has butyl(3-hydroxybutyl)tin as its major metabolite. Limited information suggests quite rapid metabolism and elimination, with half-lives of several days. Much of an oral dose of dioctyltin was eliminated in the faeces, with the remainder in urine. 

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