OGDH

Last update 08 May 2025

Basic Info

Synonyms

2-oxoglutarate dehydrogenase complex component E1, 2-oxoglutarate dehydrogenase, mitochondrial, Alpha-ketoglutarate dehydrogenase

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Introduction

2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC) (PubMed:24495017, PubMed:25210035, PubMed:28435050). Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the whole OGDHC (PubMed:24495017, PubMed:25210035, PubMed:28435050). Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST) (PubMed:24495017, PubMed:25210035, PubMed:28435050, PubMed:35272141). Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids (PubMed:25210035). Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate (PubMed:28435050). Mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).

100 Clinical Results associated with OGDH

100 Translational Medicine associated with OGDH

0 Patents (Medical) associated with OGDH

1,401

Literatures (Medical) associated with OGDH

01 Jul 2025·Free Radical Biology and Medicine

Inactivation of mitochondrial pyruvate dehydrogenase by singlet oxygen involves lipoic acid oxidation, side-chain modification and structural changes

Article

Author: Gao, Qing ; Davies, Michael J ; Hägglund, Per ; Gamon, Luke F

The multi-subunit pyruvate dehydrogenase complex (PDC) plays a crucial role in glucose oxidation as it determines whether pyruvate is used for mitochondrial oxidative phosphorylation or is converted to lactate for aerobic glycolysis. PDC contains multiple lipoic acid groups, covalently attached at lysine residues to give lipoyllysine, which are responsible for acyl group transfer and critical to complex activity. We have recently reported that both free lipoic acid, and lipoyllysine in alpha-keto glutarate dehydrogenase, are highly susceptible to singlet oxygen (¹O₂)-induced oxidation. We therefore hypothesized that PDC activity and structure would be influenced by ¹O₂ (generated using Rose Bengal and light) via modification of the lipoyllysines and other residues. PDC activity was decreased by photooxidation, with this being dependent on light exposure, O₂, the presence of Rose Bengal, and D₂O consistent with ¹O₂-mediated reactions. These changes were modulated by pre-illumination addition of free lipoic acid and lipoamide. Activity loss occurred concurrently with lipoyllysine and sidechain modification (determined by mass spectrometry) and protein aggregation (detected by SDS-PAGE). Peptide mass mapping provided evidence for modification at 42 residues (Met, Trp, His and Tyr; with modification extents of 20-50 %) and each of the lipoyllysine sites (6-20 % modification). Structure modelling indicated the modifications occur across all 4 subunit types, and occur in functional domains or at multimer interfaces, consistent with damage at multiple sites contributing to the overall loss of activity. These data indicate that PDC activity and structure are susceptible to ¹O₂-induced damage with potential effects on cellular pathways of glucose metabolism.

01 Jun 2025·Marine Pollution Bulletin

Effects of temperature and salinity on CO2 fluxes dynamics and respiration metabolism in the sea cucumber Apostichopus japonicus (Selenka)

Article

Author: Gao, Qinfeng ; Mei, Yaoping ; Dong, Shuanglin ; Li, Zhao ; Xu, Yuling

Global warming has led to higher temperatures and extreme precipitation events, significantly affecting the physiological status of sea cucumbers and causing substantial economic losses in the aquaculture industry. This study explored the effects of high temperature (HT), low salinity (LS), and their combination (TS) on CO₂ fluxes at the water-air interface, energy allocation, and the expression of respiratory metabolism-related genes in sea cucumbers. The results showed that HT and/or LS treatments reduced growth performance by 8.37-21.64 % and increased respiratory metabolic carbon content by 17.85-57.68 %. Respiratory metabolizable energy increased by 22.59 % (HT) and 25.87 % (TS). Enzyme activities and gene expression of pyruvate dehydrogenase (PDH), pyruvate kinase (PK), and hexokinase (HK) in respiratory tree were significantly higher than in body wall in response to high temperature stress. Conversely, activities and gene expression of α-ketoglutarate dehydrogenase (OGDH), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) were significantly higher in body wall in response to low salinity stress. These results indicate that the respiratory tree is more responsive to high temperature, while low salinity primarily affects the body wall. CO₂ fluxes positively correlated with respiratory metabolizable energy, respiratory metabolic carbon content, and LDH activities (R > 0.51, p < 0.05), but negatively correlated with OGDH activity and specific growth rate (R > 0.50, p < 0.05). The respiratory tree's specific functions resulted in higher CO₂ fluxes in HT group compared to LS group. Furthermore, the combined stress resulted in highest CO₂ fluxes, suggesting an additive effect on the physiological metabolism of sea cucumber. This study provides insights into the adaptation mechanisms of aquatic animals to environmental stresses.

01 Jun 2025·Molecular Genetics and Metabolism

Role of BOLA3 in the mitochondrial Fe-S cluster clarified by metabolomic analysis

Article

Author: Ohtake, Akira ; Kishita, Yoshihito ; Sugiura, Ayumu ; Shimura, Masaru ; Imai-Okazaki, Atsuko ; Iijima, Hiroyuki ; Murayama, Kei ; Okazaki, Yasushi

BOLA3 is one of the proteins involved in the assembly and transport of [4Fe-4S] clusters, which are incorporated into mitochondrial respiratory chain complexes I and II, aconitase, and lipoic acid synthetase. Pathogenic variants in the BOLA3 gene cause a rare condition known as multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, characterized by life-threatening lactic acidosis, nonketotic hyperglycinemia, and hypertrophic cardiomyopathy. The aim of this study was to elucidate the biochemical characteristics of patients with BOLA3 variants and to clarify the role of BOLA3 protein in humans. The characteristics, clinical course, and biochemical data of eight Japanese patients with BOLA3 pathogenic variants were collected. In addition, metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry, blue native polyacrylamide gel electrophoresis (BN-PAGE)/Western blot analysis of mitochondrial respiratory chain complexes, and in-gel enzyme staining of mitochondrial respiratory chain complexes of fibroblasts from all eight patients. Metabolomic data were compared between the eight patients with BOLA3 variants and three control samples using Welch's t-test. In the metabolomic analysis, levels of lactic acid, pyruvic acid, alanine, tricarboxylic acid (TCA) cycle intermediates (such as α-ketoglutaric acid and succinic acid), branched-chain amino acids, and metabolites of lysine and tryptophan were significantly elevated in the BOLA3 group. Data collected during the patients' lives showed increased lactic acid and glycine levels. In BN-PAGE/Western blot analysis and in-gel enzyme staining, bands for complexes I and II were barely detectable in all eight cases. These results indicate that BOLA3 variants decrease the activity of lipoic acid-dependent proteins (pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase, 2-oxoadipate dehydrogenase, branched-chain ketoacid dehydrogenase, and the glycine cleavage system), as well as mitochondrial respiratory chain complexes I and II, but do not affect aconitase. Thus, it is believed that BOLA3 is involved in transporting [4Fe-4S] clusters to respiratory chain complexes I and II and lipoic acid synthetase, but does not interfere with aconitase. These findings suggest that while lipoic acid supplementation or vitamin cocktails may provide benefits, the impaired [4Fe-4S] cluster pathway itself should be targeted for treatment to improve the extensive metabolic abnormalities caused by BOLA3 deficiency.

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OGDH

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