Excretion by Mammals

By the middle of the nineteenth century it was generally accepted that nitrogen was excreted by mammals as urea, and by 1905 Folin had shown that the amount of urea voided through the kidneys as urine was proportional to the level of protein in the diet. Normally 20-30 g urea are excreted by man per day protein intake also affects urine volume, which is usually 1.2-1.5 L per day. 

Ureas are diamides of carbonic acid, with two nitrogen atoms bonded to the carbonyl group. The unsubstituted urea, simply called urea, is the waste product excreted by mammals from the metabolism of excess protein. 

Dichlorvos is rapidly metabolized and excreted by mammals following any route of exposure. 

Molecular model of urea. Urea is the diamide of carbonic acid. It is excreted by mammals as a waste product from the metabolism of protein. 

Tryptophan can be converted to indolepyruvic acid either by oxidative deamination or by transamination (e.g., 739, 912) and the indolepyruvic acid can give rise to indoleacetic acid. The fate of indoleacetic acid formed by the bacterial flora of the mammalian gut is discussed below. Bacterial indolelactic acid (e.g., 757) is presumably derived from indolepyruvic acid, but indolelactic acid excreted by mammals (e.g. 17) may be of true mammalian rather than bacterial origin. Indolepropionic acid can also be formed by bacteria (e.g., 412, 633), but further metabolism in mammals of any indolepropionic acid formed in the gut is still obscure (904). Skatole (3-methylindole) has long been known as a product of bacterial decomposition of protein and is formed from tryptophan not only by the bacterial flora of the gut but also in putrefying secretions, e.g., sputum (756). It may well arise by decarboxylation of indoleacetic acid. 

Urinary indican is the 0-sulfate of indoxyl (usually isolated as the potassium salt, 414) and is excreted by mammals as a detoxication product of the... 

Because chemists could not create life in the laboratory, they assumed they could not create compounds with a vital force. With this mind-set, you can imagine how surprised chemists were in 1828 when Friedrich Wohler produced urea—a compound known to be excreted by mammals— by heating ammonium cyanate, an inorganic mineral. 

Decay in organisms relates to toxicity, and half-lives and excretion rates are dealt with elsewhere in this chapter. Toxicity arises because of easy absorption in mammals, leading to the loss of one alkyl group to form the trialkyl species. It is these trialkyl species which can most easily deliver lead and so cause toxicity. Decay does therefore take place by sequential loss of alkyl groups (similar to organotin species. Section 12.13.9), and so a series of alkyl, ionic, and inorganic lead species are excreted by mammals. 

Explain how foreign aromatic compounds are detoxified and excreted by mammals. Describe a possible deleterious effect of this process. 

The second case refers to hormones, pharmaceuticals, and other compounds that are ingested, metabolized, and excreted by mammals (Table 1). Usually a hormone or pharmaceutical is extensively metabohzed in the body and is excreted by mammals as a mixture of different metabolites. Although the general belief is that metabolism renders a drug more water soluble and consequently less hazardous for the aquatic environment, there are exceptions for pro-drugs and specifically acting metabolites. The third case refers to environmental transformation products of pesticides and other environmental pollutants (Table 1), which are formed both by abiotic and biotic transformation processes. 

Carbonic acid (H2CO3) is formed when carbon dioxide dissolves in water. Although carbonic acid itself is always in equilibrium with carbon dioxide and water, it has several important stable derivatives. Carbonate esters are diesters of carbonic acid, with two alkoxy groups replacing the hydroxyl groups of carbonic acid. Ureas are diamides of carbonic acid, with two nitrogen atoms bonded to the carbonyl group. The unsubstituted urea, simply called urem, is the waste product excreted by mammals from the metabolism of excess protein. Carbamate esters (urethanes) are the stable esters of the unstable carbamic acid, the monoamide of carbonic acid. 

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. 

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. 

Unchanged p,p -DDT tends to be lost only very slowly by land vertebrates. There can, however, be a certain amount of excretion by females into milk or across the placenta into the developing embryo (mammals) or into eggs (birds, reptiles, and insects). 

Retention of radiocopper injected into humans is high only 10% is excreted within 72 h in urine and feces, and 50% in four weeks (Aaseth and Norseth 1986). Most (72%) of the unabsorbed copper is excreted in the feces primarily by way of the biliary duct, the salivary glands, or the intestinal mucosa a minor portion is excreted by way of sweat and menses (Schroeder et al. 1966 USEPA 1980 ATSDR 1990). In mammals, copper is excreted mainly via the bile in association with glutathione or unidentified high-molecular-weight molecules. However, the transport mechanisms of copper from liver cells into bile are essentially unknown (Aaseth and Norseth 1986). In rats, biliary excretion of copper is increased by increased flow of bile, increased body temperature, or administration of adrenal steroids (Sugawara et al. 1994). 

Famphur and other organophosphorus compounds are metabolized and excreted with greater efficiency by mammals than the target pests before these compounds can bind to and ultimately inhibit the cholinesterase enzyme (Randell and Bradley 1980). Mice, for example, degrade famphur rapidly. Less than 1 h after an intraperitoneal injection of 1 mg famphur/kg BW, only 8.34% of... 

In biological samples, fenvalerate neither persists for lengthy periods nor is readily accumulated (Smith and Stratton 1986 Cooper 1991). In general, fenvalerate is rapidly (i.e., Tb 1/2 of 6 to 14 h) excreted by amphibians, birds, and mammals has low persistence in various reptiles, terrestrial... 

Most marine mammals are exposed to relatively high concentrations of those contaminants considered to be persistent (do not breakdown readily in the environment), bioaccumulative (are not readily metabolized and excreted by biota in aquatic food webs), and (immuno)toxic. Candidates in this category include various congeners of... 

Proteins are likewise broken down by microorganisms, or eaten by mammals and hydrolyzed by enzymes to amino acids. These are further oxidized to NH3, H20, and C02, releasing energy. These inorganic compounds can be utilized by living organisms to synthesize proteins, or they can be excreted. Bacteria convert ammonia to nitrites and nitrates, which plants can convert to amino acids. 

That idea was compieteiy changed by the German chemist Friedrich Wohier (1800-1882). He synthesized urea, the end product of nitrogen excretion in mammals, and became the first scientist to synthesize an organic compound from an inorganic compound. 

Pantothenic acid is largely excreted unchanged by mammals. Some phos-phopantetheine may also be excreted in the urine after administration of pantothenic acid, some of the label may be recovered in exhaled CO2. This is probably the result of intestinal bacterial metabolism, because many bacteria have pantothenase, a specific amidase that cleaves pantothenic acid to 8-alanine and pantoic acid. Pseudomonas species are capable of using pantothenic acid as their sole carbon source. 

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