Thiamine Deficiency and the in vivo Oxidation of Lactate and Pyruvate Labeled with Carbon14

Abstract

Each of three groups of thiamine-deficient mice was given one of the following: lactate-1-C¹⁴, lactate-2, 3-C¹⁴ or pyruvate-2-C¹⁴, and the activity of the respiratory carbon dioxide was determined. Each deficient animal had a pair-fed control which received the same labeled compound. Respiratory carbon dioxide was collected for three hours at hourly intervals. The average specific activity of the expired carbon dioxide was essentially the same in deficient and control animals for each hour and for all three experiments. The total carbon dioxide and hence the total count was consistently higher for the controls than for the deficient animals but in no case was the difference statistically significant. In another experiment, in which pyruvate-2-C¹⁴ was used, the carbon dioxide was collected in 5, 5, 10 and 20-minute periods. The amounts and activities of the carbon dioxide for the first two periods were very low, but the specific activity for these two periods was significantly greater for the controls when the data were treated as paired but not when treated as unpaired. The differences between activities for the other two periods were not significant. Oxidation of the pyruvate by the deficient and control groups in this experiment was slight (about 3%). No significant differences were noted in the specific activities when the deficiency was produced with either oxythiamine or pyrithiamine. However, the averages in the oxythiamine experiment were higher for the controls in all periods. Oxythiamine produced a significant difference in total counts in the second and fifth periods. Possibly oxythiamine specifically inhibited the oxidation of pyruvate to a significant but limited extent. In the pyrithiamine experiment the controls were significantly higher in total counts in the third period when the data were considered as nonpaired. By considering the specific activity and total count it is possible to compare the deficient and control groups in respect to the percentage of total carbon dioxide which originates in the labeled compound, regardless of the total amount of carbon dioxide expired. The significance of these results is discussed from this point of view. These data negate the possibility that the production of carbon dioxide from pyruvate by thiamine-deficient mice is due to randomization, and strongly support the thesis that the symptoms and signs of thiamine deficiency as seen in laboratory mammals are not the result of a specific failure on the part of the intact animal to decarboxylate pyruvate.