TCA cycle and deficiency of pyruvate dehydrogenase complex (PDHc)

When transported into the inner mitochondrial matrix, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase, PC (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH), the first enzyme of the PDH complex (PDHc). With a high cell-energy charge, co-enzyme A (CoA) is highly acylated, principally as acetyl-CoA, and able to obligately activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low, CoA is not acylated, therefore, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDHc and the TCA cycle to CO2 and H2O. The acetyl-CoA produced by the PDHc enters the TCA cycle and the reduced electron carriers (NADH and FADH2) that are generated during the oxidative reactions can then be used to drive ATP synthesis via oxidative phosphorylation. Description source: [https://themedicalbiochemistrypage.org/tca-cycle.php The Medical Biochemistryp Page] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2453 CPTAC Assay Portal].

当丙酮酸被转运至线粒体基质内部时，遭遇两种主要的代谢酶：丙酮酸羧化酶，PC（一种糖异生酶）以及丙酮酸脱氢酶（PDH），即PDH复合物（PDHc）中的首酶。在高细胞能量电荷状态下，辅酶A（CoA）高度酰化，主要形成乙酰-CoA，从而强制激活丙酮酸羧化酶，引导丙酮酸走向糖异生途径。当能量电荷较低时，CoA未发生酰化，因此丙酮酸羧化酶处于非活性状态，丙酮酸则优先通过PDHc和三羧酸循环代谢为CO2和H2O。PDHc生成的乙酰-CoA进入三羧酸循环，而在氧化反应过程中产生的还原型电子载体（NADH和FADH2）随后可用于驱动ATP的合成，通过氧化磷酸化途径。该途径中的蛋白质均有针对性的检测方法，可通过CPTAC检测门户获取，详情请见[https://assays.cancer.gov/available_assays?wp_id=WP2453]。
Description source: [https://themedicalbiochemistrypage.org/tca-cycle.php The Medical Biochemistryp Page]