Biochemical Acid Research Studies

Dichloroacetate improves animal survival, growth, neuromuscular activity, mitochondrial stress and physiology, and elevated lactate in C. elegans pdha-1 and dld-1 RNAi models of pyruvate dehydrogenase complex deficiency (PDCD)

This paper shows that DCA improves survival, growth, neuromuscular activity, mitochondrial function, and reduces lactate in C. elegans models of PDHc deficiency.

Substrate specificity in lipoylation pathways: How lipoate:protein ligases discriminate between protein substrates

This study investigates how lipoate:protein ligases distinguish between structurally similar protein substrates by analyzing electrostatic surface interactions and sequence preferences.

Functional partitioning of lipoic acid decouples cellular abundance from mitochondrial utilization

This study shows that lipoic acid exists in two distinct cellular pools with different functions, and supplementation increases free LA without restoring mitochondrial function.

Amino Acids in the RSSY Motif of Lipoyl Synthase Control Substrate Binding and Reactivity

This paper investigates the role of amino acids in the RSSY motif of lipoyl synthase, showing that Arg306 and Ser308 are critical for substrate binding and catalytic activity, with specific substitutions affecting product formation and cluster stability.

Rethinking suicide Thi4 thiazole synthases: comparative genomic insights and pilot functional evidence

This paper investigates suicide Thi4 thiazole synthases, showing genomic evidence suggesting non-suicidal function and supporting this with functional experiments in E. coli.

Mitochondrial copper stabilizes lipoylated TCA cycle proteins to sustain metabolism and proliferation

This study shows mitochondrial copper stabilizes lipoylated TCA cycle proteins, maintaining metabolism and proliferation by supporting lipoylation and TCA cycle function.

A nested shell structure coordinates enzyme communication in pyruvate oxidation

This paper proposes a multi-scale model of the pyruvate dehydrogenase complex (PDHc) revealing a nested shell structure that coordinates enzyme communication during pyruvate oxidation.

MitoSAM-dependent lipoylation controls postnatal heart development via metabolic remodeling

This study shows that mitoSAM-dependent lipoylation is essential for postnatal heart development by enabling metabolic remodeling from glycolysis to oxidative phosphorylation.

Bacterial lipoate protein ligases rescue lipoylation and respiration deficiency in mammals

This study introduces bacterial lipoate protein ligases to restore lipoylation and respiration in human and mouse models with lipoylation pathway deficiencies.

ABHD11 mediated deglutarylation regulates the TCA cycle and T cell metabolism

This study identifies ABHD11 as a deglutarylating enzyme that regulates T cell metabolism by maintaining TCA cycle integrity through removal of glutaryl-lipoyl adducts.

Trihydroxybenzaldoximes are redox cycling inhibitors of ThDP-dependent DXP synthase

This study investigates how trihydroxybenzaldoximes inhibit ThDP-dependent DXP synthase by acting as redox cycling agents, showing their oxidation under aerobic conditions enhances inhibitory activity.

GCS-H2 is essential for growth as it acts as the main relay for mitochondrial lipoylation in heterotrophic tissues of Arabidopsis thaliana

The absence of GCS-H2, an isoform of H-protein found in heterotrophic tissue, impedes the cell cycle, and drastically affects plant growth as it acts as the main relay for mitochondrial lipoylation.

Structures and comparison of endogenous 2-oxoglutarate and pyruvate dehydrogenase complexes from bovine kidney

The paper reports cryoEM structures of endogenous 2-oxoglutarate and pyruvate dehydrogenase complexes from bovine kidney, revealing structural differences and insights into their organization.

Structure and function of aerotolerant, multiple-turnover THI4 thiazole synthases

The paper identifies aerotolerant, multiple-turnover THI4 thiazole synthases in aerobic prokaryotes and shows they use cobalt as a cofactor instead of iron.

BCKDK regulates the TCA cycle through PDC to ensure embryonic development in the absence of PDK family

The paper shows that BCKDK compensates for PDK family loss by inactivating PDC, maintaining TCA cycle function and embryonic development in mice.

Genetic dissection of the mitochondrial lipoylation pathway in yeast

The paper characterizes the mitochondrial lipoylation pathway in yeast, showing it can use free lipoic acid and octanoic acid as substrates when activating enzymes are mitochondrial-targeted, and reveals conserved features in mammalian mitochondria.

Assembly and symmetry of the fungal E3BP-containing core of the Pyruvate Dehydrogenase Complex

The paper uses cryo-EM to study the structure of the fungal pyruvate dehydrogenase complex, revealing two PX oligomer arrangements that explain stoichiometry variation and suggest therapeutic targets.