Figure 2.

Labeling pattern obtained from the metabolism of [2-¹³C]acetyl-L-carnitine via the TCA cycle in rat brain. Labeling pattern from the first and “n^th” turns of the cycle are shown. Black circles indicate carbons labeled from metabolism in the first turn of the TCA cycle; grey circles are labeled from metabolism in the second and later turns of the TCA cycle. Open circles are carbons that are not labeled from the metabolism of [2-¹³C]ALCAR via the TCA cycle. [2-¹³C]acetyl-L-carnitine is converted to [2-¹³C]acetyl CoA which condenses with unlabeled oxaloacetate to form labeled citrate which is metabolized via the TCA cycle, giving rise [4-¹³C]α-ketoglutarate in the first turn. [4-¹³C]α-ketoglutarate can be converted to [4-¹³C]glutamate (GLU C4), which can be converted to [2-¹³C]GABA in GABAergic neurons. In astrocytes, [4-¹³C]Glutamate can be converted to [4-¹³C]glutamine by the enzyme glutamine synthetase. [4-¹³C]α-ketoglutarate can remain in the TCA cycle leading to formation of [3-¹³C]fumarate, which is a symmetrical molecule so randomization of the label occurs leading to some labeling in the 2 position as well. The same labeling pattern occurs in malate. [3-¹³C]Oxaloacetate and [2-¹³C]oxaloacetate formed in the first turn of the TCA cycle can be converted to [3-¹³C]aspartate (ASP C3) and also [2-¹³C]aspartate (ASP C2). GLN C3 and GLU C3 are formed after metabolism in the second turn of the cycle, and ASP C2 can also be formed. Abbreviations: GLU, glutamate; GLN, glutamine; MAL, malate; OAA, oxaloacetate.