604-98-8

Usage

Uses

Used in Energy Production:
S-(hydrogen succinyl)coenzyme A is used as a catalyst in the citric acid cycle for the conversion of succinyl-CoA to succinate, which is essential for the production of high-energy molecules like ATP and NADH, providing energy for cellular processes.
Used in Heme Synthesis:
In the synthesis of heme, S-(hydrogen succinyl)coenzyme A is used as a precursor for the production of heme groups, which are crucial for the function of hemoglobin and other hemoproteins involved in oxygen transport and storage.
Used in Cellular Metabolism Regulation:
S-(hydrogen succinyl)coenzyme A is utilized as a regulatory molecule in cellular metabolism, playing a role in the maintenance of metabolic homeostasis and having implications for the study and treatment of various metabolic disorders.
Used in Pharmaceutical and Biomedical Research:
S-(hydrogen succinyl)coenzyme A is employed as a target or tool in pharmaceutical and biomedical research to understand and develop treatments for metabolic disorders and diseases related to energy production and cellular metabolism.

Upstream product

• 108-30-5 succinic acid anhydride 
• 85-61-0 coenzyme A 
• 1264-45-5 (2RS)-methylmalonyl-CoA 
• 18439-24-2 coenzyme A lithium salt 
• 110-15-6 succinic acid 
• 72-89-9 acetylcoenzyme A 

Downstream Products

• 106-60-5 ALA 
• 85-61-0 coenzyme A 
• 72-89-9 acetylcoenzyme A 
• 317-66-8 S-propionyl-coenzyme-A 
• 3131-84-8 glutaryl-CoA 
• 524-14-1 S-(hydrogen malonyl)coenzyme A 
• 92256-33-2 N-(2-indol-3-yl-ethyl)-succinamic acid 

Relevant academic research and scientific papers

Tyrosine 89 accelerates Co-carbon bond homolysis in methylmalonyl-CoA mutase

The contribution of the active-site residue, Y89, to the trillion-fold acceleration of Co-carbon bond homolysis rate in the methylmalonyl-CoA mutase-catalyzed reaction has been evaluated by site-directed mutagenesis. Conversion of Y89 to phenylalanine or alanine results in a 103-fold diminution of kcat and suppression of the overall kinetic isotope effect. The spectrum of the enzyme under steady-state conditions reveals the presence of AdoCbl but no cob(II)alamin. Together, these results are consistent with homolysis becoming completely rate determining in the forward direction in the two mutants and points to the role of Y89 as a molecular wedge in accelerating Co-carbon bond cleavage.

A method for trapping intermediates of polyketide biosynthesis with a nonhydrolyzable malonyl-coenzyme A analogue

(Chemical Equation Presented) Trapped in the middle: To investigate the mechanistic details of polyketide biosynthesis, intermediates are trapped by a nonhydrolyzable malonyl-coenzyme A analogue that reacts with a growing polyketide chain formed by a stilbene synthase. As the reverse transesterification reaction is not possible, the polyketide intermediates accumulate attached to the analogue (see scheme; Enz = enzyme, CoA = coenzyme A).

Functional chararacterization of the enzymes TabB and TabD involved in tabtoxin biosynthesis by Pseudomonas syringae

Pseudomonas syringae pv. tabaci ATCC 11528 produces tabtoxin, a β-lactam-containing dipeptide phytotoxin. Tabtoxinine-β-lactam (TβL), one of tabtoxin's constituent amino acids, structurally mimics lysine, and many of the proteins encoded by the tabtoxin biosynthetic gene cluster are homologs of lysine biosynthetic enzymes, suggesting that the tabtoxin and lysine biosynthetic routes parallel one another. We cloned and expressed TabB and TabD, predicted homologs of tetrahydrodipicolinate (THDPA)-N-acyltransferase and N-acyl-THDPA aminotransferase, respectively, to determine their activities in vitro. We confirmed that TabB succinylates THDPA and that TabD is a PLP-dependent aminotransferase that utilizes glutamate as an amine donor. Surprisingly, we also found that though TabD could utilize the TabB product N-succinyl-THDPA as a substrate, THDPA itself was also recognized. These observations reveal that TabB functionally duplicates DapD, the THDPA-N-succinyltransferase involved in lysine biosynthesis, and reinforce the close relationship between the metabolic logics underpinning the respective biosynthetic pathways.

Novel coenzyme B12-dependent interconversion of isovaleryl-CoA and pivalyl-CoA

5′-Deoxyadenosylcobalamin (AdoCbl)-dependent isomerases catalyze carbon skeleton rearrangements using radical chemistry. We have recently characterized a fusion protein that comprises the two subunits of the AdoCbl-dependent isobutyryl- CoA mutase flanking a G-protein chaperone and named it isobutyryl-CoA mutase fused (IcmF). IcmF catalyzes the interconversion of isobutyryl-CoA and n-butyryl-CoA, whereas GTPase activity is associated with its G-protein domain. In this study, we report a novel activity associated with IcmF, i.e. the interconversion of isovaleryl-CoA and pivalyl-CoA. Kinetic characterization of IcmF yielded the following values: a Km for isovaleryl-CoA of 62 ± 8 μM and Vmax of 0.021 ± 0.004 μmol min-1 mg-1 at 37 ° C. Biochemical experiments show that an IcmF in which the base specificity loop motif NKXD is modified to NKXE catalyzes the hydrolysis of both GTP and ATP. IcmF is susceptible to rapid inactivation during turnover, and GTP conferred modest protection during utilization of isovaleryl-CoA as substrate. Interestingly, there was no protection from inactivation when either isobutyryl-CoA or n-butyryl-CoA was used as substrate. Detailed kinetic analysis indicated that inactivation is associated with loss of the 5′-deoxyadenosine moiety from the active site, precluding reformation of AdoCbl at the end of the turnover cycle. Under aerobic conditions, oxidation of the cob(II)alamin radical in the inactive enzyme results in accumulation of aquacobalamin. Because pivalic acid found in sludge can be used as a carbon source by some bacteria and isovaleryl- CoA is an intermediate in leucine catabolism, our discovery of a new isomerase activity associated with IcmF expands its metabolic potential.

Crystal structures of Acetobacter aceti succinyl-coenzyme A (CoA):Acetate CoA-transferase reveal specificity determinants and illustrate the mechanism used by class i CoA-transferases

Coenzyme A (CoA)-transferases catalyze transthioesterification reactions involving acyl-CoA substrates, using an active-site carboxylate to form covalent acyl anhydride and CoA thioester adducts. Mechanistic studies of class I CoA-transferases suggested that acyl-CoA binding energy is used to accelerate rate-limiting acyl transfers by compressing the substrate thioester tightly against the catalytic glutamate [White, H., and Jencks, W. P. (1976) J. Biol. Chem. 251, 1688-1699]. The class I CoA-transferase succinyl-CoA:acetate CoA-transferase is an acetic acid resistance factor (AarC) with a role in a variant citric acid cycle in Acetobacter aceti. In an effort to identify residues involved in substrate recognition, X-ray crystal structures of a C-terminally His6-tagged form (AarCH6) were determined for several wild-type and mutant complexes, including freeze-trapped acetylglutamyl anhydride and glutamyl-CoA thioester adducts. The latter shows the acetate product bound to an auxiliary site that is required for efficient carboxylate substrate recognition. A mutant in which the catalytic glutamate was changed to an alanine crystallized in a closed complex containing dethiaacetyl-CoA, which adopts an unusual curled conformation. A model of the acetyl-CoA Michaelis complex demonstrates the compression anticipated four decades ago by Jencks and reveals that the nucleophilic glutamate is held at a near-ideal angle for attack as the thioester oxygen is forced into an oxyanion hole composed of Gly388 NH and CoA N2″. CoA is nearly immobile along its entire length during all stages of the enzyme reaction. Spatial and sequence conservation of key residues indicates that this mechanism is general among class I CoA-transferases.