Figure 3.

Labeling pattern obtained from the metabolism of [2-¹³C]ALCAR via the pyruvate recycling pathway in brain. The initial labeling of OAA and malate from metabolism of [2-¹³C]ALCAR in the TCA cycle is show in the bottom left section of the figure. The [3-¹³C]malate, [2-¹³C]malate and [3-¹³C]oxaloacetate and [2-¹³C]oxaloacetate formed from metabolism of labeled ALCAR in the TCA cycle are converted to pyruvate via either malic enzyme or the combined action of pyruvate kinase and PEPCK, respectively. The labeled pyruvate formed can be converted to lactate and/or alanine labeled in the C1, C2 or C3 positions (‘partial’ recycling pathway). If ‘complete’ recycling occurs the labeled pyruvate formed is converted to acetyl CoA labeled in the C1 position which condenses with citrate in the TCA cycle and gives rise to [5-¹³C]–α-ketoglutarate and subsequently GLU C5 and GLN C5. [1-¹³C]–α-ketoglutarate and GLU C1 and GLN C1 is labeled from further metabolism of the [5-¹³C]–α-ketoglutarate formed from recycling via subsequent turns of the TCA cycle. Although, pyruvate recycling can give rise to acetyl CoA labeled in the C2 position, it is not possible to distinguish this from the [2-¹³C]acetyl CoA formed directly from [2-¹³C]ALCAR.