Anaplerosis in action

Abstract

Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the need for future therapies aimed at replenishing intermediates of the tricarboxylic acid cycle.

Figure 1 |. Dysregulation of anaplerosis and the TCA cycle in MMA.

A summary of alterations seen in the TCA cycle and TCA anaplerotic pathways in the context of MMA. The red symbol over MMUT represents loss of protein function in MMA. Green arrows indicate noted increase in protein activity and/or expression or increased metabolite level in MMA. Red arrows indicate decreased protein activity and/or expression or metabolite level in MMA. Dashed lines indicate potential protein–protein complex formation or direct protein–protein interactions. Dimethyl-oxoglutarate is highlighted in green with an arrow to indicate where supplementation of the small molecule would occur in the TCA cycle.