Carbon dioxide, labeled excretion

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. 

Root products, as defined by Uren and Reisenauer (17), represent a wide range of compounds. Only secretions are deemed to have a direct and immediate functional role in the rhizosphere. Carbon dioxide, although labeled an excretion, may play a role in rhizosphere processes such as hyphal elongation of vesicular-arbuscular mycorrhiza (39). Also, root-derived CO2 may have an effect on nonphotosynthetic fixation of CO2 by roots subject to P deficiency and thus contribute to exudation of large amounts of citrate and malate, as observed in white lupins (40). The amounts utilized are very small and, in any case, are extremely difficult to distinguish from endogenous CO2 derived from soil and rhizosphere respiration. 

No studies were located regarding excretion of bromomethane by humans after oral exposure. One study in animals indicates that the rate and pattern of excretion of C-label following oral exposure to C- bromomethane is similar to that following inhalation exposure 32% was exhaled as carbon dioxide, 43% was excreted in the urine, 4% of unmetabolized parent compound was exhaled, 2% was excreted in the feces, and 14% remained in the body after 72 hours (Medinsky et al. 1984). 

Excretion of radioactivity in mice and rats was monitored for 48 hours following exposure to " C-labeled chloroform (Corley et al. 1990). In general, 92-99% of the total radioactivity was recovered in mice, and 58-98% was recovered in rats percentage of recovery decreased with increasing exposure. With increasing concentration, mice exhaled 80-85% of the total radioactivity recovered as " C-labeled carbon dioxide, 0.4-8% as " C-labeled chloroform, and 8-11 and 0.6-1.4% as urinary and fecal metabolites, respectively. Rats exhaled 48-85% of the total radioactivity as " C-labeled carbon dioxide, 2-42% as " C-labeled chloroform, and 8-11 and 0.1-0.6% in the urine and feces, respectively. A 4-fold increase in exposure concentration was followed by a 50- and 20-fold increase in the amount of exhaled, unmetabolized chloroform in mice and rats, respectively. 

Following a single, oral exposure, most of the 0.5 grams of radioactively labeled chloroform administered to volunteers was exhaled during the first 8 hours after exposure (Fry et al. 1972). A slower rate of pulmonary excretion was observed during the first eight hours in volunteers who had more adipose tissue than the other volunteers. Up to 68.3% of the dose was excreted unchanged, and up to 50.6% was excreted as carbon dioxide. A positive correlation was made between pulmonary excretion and blood concentration. Less than 1% of the radioactivity was detected in the urine. 

A very small portion of the absorbed hexachlorobutadiene is oxidized to carbon dioxide. This pathway can be saturated since an increase in the hexachlorobutadiene dose does not cause a corresponding increase in excretion of labeled carbon dioxide (Dekant et al. 1988b Payan et al. 1991 Reichert et al. 1985). 

Radiolabeled benzene (=340 mg/kg) was administered by oral intubation to rabbits 43% of the label was recovered as exhaled unmetabolized benzene and 1.5% was recovered as carbon dioxide (Parke and Williams 1953). Urinary excretion accounted for about 33% of the dose. The isolated urinary metabolites were mainly in the form of conjugated phenols. Phenol was the major metabolite accounting for about 23% of the dose or about 70% of the benzene metabolized and excreted in the urine. The other phenols excreted (percentage of dose) were hydroquinone (4.8%), catechol (2.2%), and trihydroxybenzene (0.3%). L-phenyl-N-acetyl cysteine accounted for 0.5% of the dose. Muconic acid accounted for 1.3% the rest of the radioactivity (5-10%) remained in the tissues or was excreted in the feces (Parke and Williams 1953). 

A DHA lactonase has been described (76,77) in the ox, rabbit, rat, and guinea pig. In the ox the lactonase is present in several tissues but is most abundant in the liver. The enzyme appears to be absent in human and monkey tissue. This result is consistent with the observation that primates and fishes do not catabolize labeled ascorbic acid to carbon dioxide. AA and DHA appear to be metabolized into a series of water soluble products that are excreted in the urine, but 2,3-DKG is decar-boxylated and otherwise degraded to intermediates that enter the C5 and C4 carbohydrate pools (78). 

The course of carbon-14-radioactivity derived from oral (l- C)ascorbic acid in plasma and several tissues was studied in male guinea pigs up to 320 h after intake. The excretion of label was followed in respiratory carbon dioxide, urine, and feces. The evaluation by pharmacokinetic principles yielded an overall half-life of 61 h and a body pool of 21 mg with a total turnover of about 10 mg/d. The total turnover of ascorbate is lower than the daily intake (16 mg/d), indicating incomplete absorption. Ascorbic acid seemed to be bound in several tissues (adrenals, testes) to a higher percentage than in plasma. The maximum rate of excretion as carbon dioxide occurred at 0.5 h, whereas peak concentration of radioactivity in plasma was reached at 1.5 h. Therefore, presystemic metabolism must be considered. 

Excretion of C-Radioactivity. The maximum rate of excretion (10 dpm/h) of C-radioactivity as carbon dioxide is reached at about 0.5 h (Figure 6). However, the peak in activity vs. time curves of plasma and of the rapidly perfused organs like liver, lungs, kidney is at about 1.5 h (Figure 2). The excretion of C-radioactivity as labeled carbon dioxide is not directly related to plasma in the first time period after administration of the label. An intermediate compartment X3 must be assumed. 

In guinea pigs there is considerable conversion of ascorbic acid to respiratory carbon dioxide (3,37). Further, the entire carbon chain of ascorbic acid is subjected to extensive oxidation to carbon dioxide (3,21), Following injection of (1- C)ascorbic acid, 66% of the label was recovered as ( C)carbon dioxide during 10 d up to 30-40% of the dose was catabolized to carbon dioxide during the first 24 h (20). Our data indicate that in a time period of 216 h about 65% of the oral dose of (1- C)ascorbic acid is exhaled as labeled carbon dioxide (Table I). The maximum rate of excretion occurred at 0.5 h (Figure 6), and we derived from this radioactivity-time curve that within the first 12 h about 30% of the label was exhaled (36% after 24 h). 

Hymexazole is virtually nontoxic to mammals and aquatic animals. Its acute oral LD50 for rats is 4000 mg/kg (Okudaira, 1973). In tests with -labelled hymexazole it was found that the active substance is rapidly absorbed and distributed in the rat tissues, but within 96 hours 97% of the total active material is excreted in the urine and 0,89% in the feces. Two metabolites have been identified in the urine 3-0 -D-glucopyranosyloxy)-5-methylisoxazole and 5-methyl-3-isoxazolyl sulfate (Nagakawa and Ando, 1973 Ando et al., 1974). The hymexazole activity persists in the soil for a few weeks. Microorganisms participate in its degradation. The active substance is decomposed first into acetoacetic amide and 5-methyl-2-(3H)-oxazolone, to yield ammonia, acetone and carbon dioxid as end-products (Nakanishi, 1973). 

Animal studies using labeled triazines indicate that the herbicides are mostly excreted out within 2-3 days of administration and not retained in body tissues or fluids. However, small amounts of labeled residues (<10%) have been detected in blood, brain, heart, liver, kidney, muscle, and lung, even after a week. The nonchlorinated triazines are eliminated more rapidly than are the chlorinated compounds (ACGIH 1986). All these studies indicate that triazines do not metabolize to carbon dioxide. The mode of action... 

The metabolism of cocaine was inhibited by SKF-525A, a microsomal enzyme inhibitor. The relationship between the pharmacological activity of cocaine and its derivatives and the inhibitory action on uptake of dopamine into striatal synaptosomes has been studied. [N- " CHsjcocaine was metabolized in healthy humans the production of labelled carbon dioxide provided a measure of N-demethylation, which proved to be greater with lower plasma cholinesterase activity. Radioactivity excreted in the urine was 65-75% in 28 hours, and ecgonine methyl ester proved to be the major metabolite (32-49% of urinary metabolites). 

The total amount of urea synthesized each day is several-fold higher than the amount that is excreted. Urea diffuses readily from the bloodstream into the large intestine, where it is hydrolysed by bacterial urease to carbon dioxide and ammonium. Much of the ammonium is reabsorbed and used in the liver for the synthesis of glutamate and glutamine, and then a variety of other nitrogenous compounds. Studies with urea show that a significant amount of label is found in essential amino acids. This may reflect intestinal bacterial synthesis of amino acids, or it may reflect the reversibility of the transamination of essential amino acids. 

The first enzyme to be crystallized (and hence the first evidence that enzymes are proteins) was urease, which catalyses the hydrolysis of urea to ammonium and carbon dioxide. The original preparation of urease was from plant material, but the enzyme is also known to occur in a number of bacteria. In this study, a group of volunteers were given an intravenous infusion of 20 mmol urea labelled with both and and their urinary excretion of label was measured over 24 hours. Complete recovery of the label in urine would amount to 40 mmol and 20 mmol C. The results are shown in column 2 of Table 9.19. The experiment was repeated a week later, after they had received the antibiotic neomycin for 4 days to sterilize the gut these results are shown in column 3. 

Roth et al. (196), using C -carboxyl labeled nicotinic acid or nicotinamide, have shown that the compounds are rapidly excreted. A total of about 3% of the carboxyl group was expired as carbon dioxide within 1 day after the injection. A few more per cent is given off as exhaled carbon dioxide several days later. It has been estimated that approximately 15 % of the radioactivity fixed in the tissue is exhaled as carbon dioxide. In later studies it was shown that carbon dioxide production from labeled nicotinic acid and nicotinamide also occurs in hamsters, rats, and dogs (221). Hamsters and rats excrete somewhat more by this route, and the dog very little. This is illustrated in Fig. 10. It is of importance to note that very little of the radioactivity appears in the feces. This may be significant with regard to intestinal synthesis of the vitamin. 

From metabolic studies, an isotopic caffeine breath test has been developed that detects impaired liver function using the quantitative formation of labeled carbon dioxide as an index. From the urinary excretion of an acetylated uracil metabolite, human acet-ylator phenotype can be easily identified and the analysis of the ratio of the urinary concentrations of other metabolites represents a sensitive test to determine the hepatic enzymatic activities of xanthine oxidase and microsomal 3-methyl demethylation, 7-methyl demethylation, and 8-hydroxylation. Quantitative analyses of paraxanthine urinary metabolites may be used as a biomarker of caffeine intake. Fecal excretion is a minor elimination route, with recovery of only 2-5% of the ingested dose. 

The other known principal physiological modulators of hemoglobin besides oxygen and organic phosphate anions are protons (Bohr effect) and carbon dioxide (Kilmartin and Ross-Bernadi, 1973 Morrow et a/., 1976). Carbon dioxide is transported for excretion partly in combination with hemoglobin in the form of carbamino adducts (Bauer and Kurtz, 1977). The ESR spin-spin interactions of spin labels with hemoglobin and its derivatives have been reviewed recently (Eaton, 1978). 

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