Radioactive carbon, metabolism

Experiments involving the release of radioactive carbon dioxide from MSMA-14C treated soils were conducted in a system consisting of two test tubes connected in series. One tube contained 5g of treated soil (at 10 and lOOppm of monosodium methane arsenic acid carbon dioxide while a second tube contained a trapping mixture, 2-methoxyethanol and monoethanolamine (7-10, v/v). Carbon dioxide-free air was passed over the soil and metabolic 14CO was collected in the trapping solution. The soils studied were Sharkey cldy, Hagerstown silty clay loam, Cecil sandy loam, and Dundee silty clay loam. All soils were initially adjusted to field capacity and maintained at 28-30°C the evolved 14CO was sampled periodically. Some properties of these soils are shown in Tabfe 13.1. 

Veltishcheva, I.F. (1970). Study of metabolism in fish using radioactive carbon (In Russian). Trudy VNIRO 69,9-18. 

Three general questions about pesticides in agricultural products and the environment must be answered where is it and its metabolites, how much of these are there and what are the metabolites. The Metabolism Section of the Biochemistry Department uses a variety of analytical techniques to answer these questions. Metabolism studies are generally done with radioactive carbon which provides a convenient method for... 

If [14C]acetate (or [14C]acetyl-CoA) were injected into an animal, would radioactive carbons be found in glucose Explain your answer in terms of acetyl-CoA metabolism. 

Radioactive carbon dioxide was detected in the breath of rats and men almost immediately after the administration, either orally or by injection, of (RS)-[5-14C]MVA,36 and up to 6.5% of the administered dose was exhaled within 100 minutes. Since the carbon dioxide was not derived from the unnatural S-enantiometer of MVA, or from degradation of cholesterol biosynthesized from the additive MVA, the observations support the hypothesis that there exists a metabolic shunt of intermediates of sterol biosynthesis which, although derived from MVA, do not lead to sterol formation. The significance of this shunt is that its occurrence could explain some of the human hypercholesterolaemias. The authors claim that MVA has no metabolic fate (hitherto known) except the biosynthesis of terpenoids is quite... 

C.B. van Niel, S.F. Carlson, S. Ruben, M.D. Kamen, and J.W. Foster, Radioactive Carbon as an Indicator of Carbon Dioxide Reduction. VIII. The Role of Carbon Dioxide in Cellxtiar Metabolism, Proceedings of the National Academy of Sciences 28, 8-15, 1942. 

Biosynthetic methods are ideally suited for the synthesis of many radiolabeled compounds. Plants (e.g., potato and tobacco), when grown in the atmosphere of radioactive carbon dioxide utilize the as their sole source of carbon. After a suitable period of growth, almost every carbon atom in the plant is radioactive. In this way plants can serve as a source of labeled carbohydrates. Algae grown under similar conditions provide labeled amino acids, lipids, nucleotides, etc. Vitamin B12 is obtained from the metabolic products of microorganisms whose culture media contain cobalt-57 or cobalt-58. 

The CO2 in the atmosphere has COi in equilibrium with radioactive CO2. Radioactive carbon is formed in the upper atmosphere through the bombardment of cosmic ray neutrons on N. It is rapidly oxidised to radioactive C02 and enters the Earth s plant and animal life through photosynthesis and the food chain. Plants and animals that use carbon in biological food chains take up C during their lifetimes. They exist in equilibrium with the C concentration in the atmosphere that is, the numbers of C-14 atoms and nonradioactive carbon atoms stay approximately the same over time. As soon as a plant or animal dies, the metabolic fimction of carbon... 

The experiments with (U-l3C)AIRs showed that this nucleoside supplied all of the carbon atoms of pyramine. Because out of 6 carbon atoms of pyramine, only three may come from the imidazole part of AIRs, it can be concluded that the three other carbon atoms come from the ribose part of this nucleoside. In complete agreement with these results, radioactivity from AIRs, labeled mainly with, 4C in its ribose part, was found to incorporate into the three carbon atoms of pyramine, the origin of which was, at the time, unknown. Owing to the minute amount of AIRs supplied (as compared with that of glucose) in both experiments, the incorporation of label from AIRs after metabolic degradation is ruled out. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Metabolism was studied with halcinonide labelled with carbon-14 in the 2-position of the acetonide group. It was administered intravenously to dogs at a dose of 5 mg/kg. The major portion of the radioactivity was excreted in bile. Radio-autography of bile showed at least 10 distinct metabolites to be present. Four of the metabolites were identified. The two most abundant metabolites, that were identified, accounted for 43% (Figure 8, Ml) and 30%(M2) of the radioactivity. The two minor metabolites (M3 and M4) accounted for 2% each. In dog urine, these four metabolites (Ml-4) accounted for 10, 15, 5 and 18% of the radioactivity, respectively. In dog blood, unchanged halcinonide and metabolites M3 and M4 each accounted for about 15% of the radioactivity. Ml and M2 were not detected. 

Expired air. For 14C-labeled chemicals, the tracer carbon may be incorporated in vivo into carbon dioxide, a possible metabolic product. Therefore, when the position of the radiolabel indicates the potential for biological instability, a pilot study to collect expired air and monitor its radioactivity content should be conducted prior to initiating a full-scale study. Expired air studies should also be performed in situations where the radiolabel has been postulated to be stable but analyses of urine and feces from the toxicokinetic study fail to yield complete recovery (mass balance) of the dose. 

The nature of the radioactivity in the water, soil and fish from the carbon-14 DDT experiment was examined by thin-layer chromatography as shown in Figure 5. The radioactivity in the water was very polar in nature and did not migrate appreciably from the origin. About 78% of the radioactivity in the soil was extracted with methanol. The major metabolite in the extractable fraction was DDD which represented 33% of the total radioactivity. The reductive dechlorination of DDT to DDD is a known pathway under anaerobic conditions and has been shown to be due to microbial metabolism (5). Since carbon-14 DDT was incor-... 

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