大部分正常细胞葡萄糖产生的丙酮酸进入线粒体并在 丙酮酸脱氢酶 （PDH）作用下被代谢为乙酰辅酶A（Ac-CoA），从而进入TCA循环为细胞供能（图0）。 但在内皮细胞中，谷氨酰胺是为TCA循环提供碳的主要物质。 由于PDH激酶（PDK）对PDH的磷酸化抑制了内皮细胞线粒体对丙酮酸的分解，从而使内皮细胞的丙酮酸被 乳酸脱氢酶 （LDH）氢化为乳酸（与癌细胞的葡萄糖代谢类似）。 PDK通过磷酸化PDH的E1限速亚基抑制PDH，最近有文章指出，PDH异常激活会 …

Pyruvate dehydrogenase (PDH) connects glycolysis with the mitochondrial tricarboxylic acid (TCA) cycle. Soriano-Baguet et al. show that PDH directs a glucose-derived citrate pool that coordinates the central carbon metabolism and histone …

Jul 19, 2023 · We observed the translocation of selected mitochondrial tricarboxylic acid (TCA) cycle dehydrogenases to the nucleus as an adaptive stress response to anthracycline-cardiotoxicity in human...

May 26, 2022 · Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial...

Dec 2, 2022 · Here we show that TCA cycle enzymes including Pdha1, Pcb, Aco2, Cs, Idh3a, Ogdh, Sdha and Mdh2 are translocated to the nucleus during somatic cell reprogramming, primed-to-naive transition and...

Feb 19, 2025 · 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).

Mar 28, 2024 · We found that pyrimidines, but not purines, maintain pyruvate oxidation and the tricarboxylic citric acid (TCA) cycle by regulating pyruvate dehydrogenase (PDH) activity. PDH activity requires sufficient substrates and cofactors, including thiamine pyrophosphate (TPP).

Sep 7, 2021 · In vivo labeling studies and metabolomic analyses offered mechanistic insights into why T cells depend upon PDH. Thymocytes and T-ALL required PDH activity for entry of glucose carbons into TCA cycle intermediates, whereas HSCs and bone marrow cells appeared to preferentially use alternative fuels to supply the TCA cycle in vivo.

Oct 15, 2020 · Here, we show that AMPK (AMP-activated protein kinase), activated in mouse metastasis models, drives pyruvate dehydrogenase complex (PDHc) activation to maintain TCA cycle (tricarboxylic acid cycle) and promotes cancer metastasis by adapting cancer cells to metabolic and oxidative stresses.

Nov 25, 2020 · Mechanistically, AMPK was shown to co-localize with PDHA, the catalytic subunit of PDH, in the mitochondrial matrix and directly triggered the phosphorylation of PDHA on Ser295 and Ser314. Hyper-phosphorylation of Ser295 and Ser314 of PDHA promotes lung metastasis through elevating activity of PDH.