Kuchel Philip W, Philp David J
School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia.
J Theor Biol. 2008 Jun 7;252(3):391-401. doi: 10.1016/j.jtbi.2007.05.039. Epub 2007 Jul 5.
The relative abundances and rates of formation of particular isotopic isomers (isotopomers) of metabolic intermediates from (13)C-labelled substrates in living cells provide information on the routes taken by the initial (13)C-atoms. When a primary substrate such as [U,(13)C] d-glucose is added to human erythrocytes, the pattern of labels in terminal metabolites is determined by a set of carbon-group exchange reactions in both glycolysis and the pentose phosphate pathway (PPP). Of a given terminal metabolite, not all possible isotopomers will be produced from each possible primary substrate isotopomer. There are only 8 different (13)C-isotopomers of lactate but not all of these are produced when one of the 64 possible (13)C-isotopomers of glucose is used as the input substrate; thus a subset of all 63 glucose isotopomers x 8 lactate isotopomers+1 unlabelled glucose x 1 unlabelled lactate=505 pattern associations, would be produced if a complete experimental analysis were performed with all the glucose variants. The pattern of labelling in this isotopomer subspace reflects the nature of the re-ordering reactions that 'direct' the metabolism. Predicting the combinatorial rearrangements for particular sets of reactions and comparing these with real data should enable conclusions to be drawn about which enzymes are involved in the real metabolic system. An example of the glycolysis-PPP system is discussed in the context of a debate that occurred around the F- and L-type PPPs and which one actually operates in the human RBC. As part of this discussion we introduce the term 'combinatorial deficit' of all possible isotopomers and we show that this deficit is less for the F- than the L-type pathway.
活细胞中来自¹³C标记底物的代谢中间体特定同位素异构体（同位素体）的相对丰度和形成速率，提供了关于初始¹³C原子所走路径的信息。当向人红细胞中添加诸如[U,¹³C]d-葡萄糖这样的主要底物时，终产物代谢物中的标记模式由糖酵解和磷酸戊糖途径（PPP）中的一组碳基团交换反应决定。对于给定的终产物代谢物，并非所有可能的同位素体都能从每种可能的主要底物同位素体产生。乳酸只有8种不同的¹³C同位素体，但当葡萄糖64种可能的¹³C同位素体之一用作输入底物时，并非所有这些同位素体都会产生；因此，如果对所有葡萄糖变体进行完整的实验分析，将产生所有63种葡萄糖同位素体×8种乳酸同位素体 + 1种未标记葡萄糖×1种未标记乳酸 = 505种模式关联。这个同位素体子空间中的标记模式反映了指导代谢的重排反应的性质。预测特定反应组的组合重排并将其与实际数据进行比较，应该能够得出关于实际代谢系统中涉及哪些酶的结论。在围绕F型和L型PPP发生的一场争论的背景下，讨论了糖酵解 - PPP系统的一个例子，以及在人类红细胞中实际起作用的是哪一种。作为该讨论的一部分，我们引入了所有可能同位素体的“组合缺陷”这一术语，并表明F型途径的这种缺陷比L型途径的要小。
