Incorporation of Tritium into Human Plasma Triglycerides from Glucose-1-³H and Lactic Acid-2-³H

Abstract

THE importance of TPNH as a specific hydrogen donor in fatty acid synthesis is well known. TPNH formed during the process of glucose oxidation through the pentose phosphate pathway is an established precursor for such synthesis¹; TPNH formed from isocitric acid oxidation may be another important source². Experiments done with glucose-1-³H in obese hyperglycæmic mice³ show a small per cent incorporation of tritium dose into body fatty acids (maximum incorporation obtained is 2 per cent). Measurement of tritium in body water of these mice indicates that 70–80 per cent of the tritium contained in the glucose-1-³H can be accounted for in body water. This low ratio of tritium in fatty acids to tritium in body water casts some doubt as to the critical need of hydrogen atoms at the 1 position of glucose in maintaining fatty acid synthesis. This doubt has been further substantiated by recent investigations⁴ with three different pairs of substrates: (1) lactic acid-2-³H and lactic acid-2-¹⁴C; (2) glucose-1-³H and glucose-1-¹⁴C; (3) glucose-6-³H and glucose-6-¹⁴C injected into obese, non-diabetic patients. Tritium content in body water and carbon-14 content in respired carbon dioxide were measured. The ³HOH : ¹⁴CO₂ ratio in the case of lactic acid has been found to remain at a level of about 3 : 1 at all times up to 2 h, whereas in the case of the other two pairs (2) and (3) the same ratio shows a value of about 6 : 1 at 30 min, gradually decreasing to about 3 : 1 at 130 min after injection. This is indirect evidence that hydrogen transferred from the carbon-1 position of glucose has very little specificity for reductive synthetic reactions compared with other metabolic sources of hydrogen.