From the Research
The intermediate linking the urea cycle with the TCA cycle is fumarate, which is produced when argininosuccinate is cleaved to form arginine, and can then enter the TCA cycle directly, where it is converted to malate by the enzyme fumarase 1. This connection creates a metabolic bridge between nitrogen disposal (urea cycle) and energy production (TCA cycle).
- The urea cycle and TCA cycle are closely linked, with the urea cycle deriving one of its nitrogens through transamination of oxalacetate to form aspartate, and returning fumarate to the TCA cycle 2.
- The interconnection of these cycles demonstrates how the body efficiently manages both nitrogen waste and energy metabolism, particularly during periods of protein catabolism when both pathways need to function coordinately.
- Additionally, aspartate, which donates its amino group in the urea cycle, is regenerated from oxaloacetate in the TCA cycle, creating another connection between these pathways 3.
- This metabolic integration is important because it allows the carbon skeleton of amino acids to be utilized for energy production after the nitrogen has been removed for excretion.
- The regulation of enzymes in the urea cycle and arginine metabolism is complex, involving transcriptional regulation by glucagon, insulin, and glucocorticoids in liver, and by pro- and antiinflammatory cytokines in nonhepatic cells 4.
- The study of argininosuccinate lyase deficiency, a urea cycle disorder, has provided insights into the importance of this intermediate step in the urea cycle and its connection to the TCA cycle 5.