HADH Antibodies

Background

The HADH gene encodes hydroxyacyl-coA dehydrogenase, which is A component of mitochondrial triple-function proteins and is mainly distributed in the mitochondrial matrix of liver and cardiomyocytes. It participates in maintaining the homeostasis of the body's energy metabolism by catalyzing the dehydrogenation reaction of hydroxyacyl-coA in the β -oxidation of fatty acids. The deficiency of this enzyme can cause the hereditary metabolic disease HADH deficiency, which is clinically manifested as hypoketogenic hypoglycemia and cardiomyopathy. The three-dimensional structure analysis of it reveals the unique tetramer conformation and substrate binding characteristics, providing an important model for the molecular diagnosis and targeted therapy research of congenital metabolic disorders, and has key scientific value for understanding the regulatory mechanism of metabolic pathways.

Structure Function Application Advantage Our Products

Structure of HADH

The mitochondrial hydroxyacyl-coA dehydrogenase encoded by the HADH gene is A tri-functional protein complex composed of approximately 34.5 kDa α subunits. This enzyme shows significant structural conservation in different species:

Species	Human	Mouse	Rat	Bovine
Molecular Weight (kDa)	34.3	34.1	34.2	34.4
Primary Structural Differences	Highly conserved catalytic domains	95% sequence homology	Similar substrate binding sites	Stable tetramer conformation

This protein is composed of 308 amino acid residues, and its three-dimensional structure presents a typical α/β folding pattern. The active center contains the key glutamate-glycine-serine tripeptide structure, which stabilizes the binding of coenzyme NAD+ through a precise hydrogen bond network. The unique "Rossmann fold" conformation is responsible for coordinating substrate recognition and catalytic processes, while conserved cysteine residues are involved in maintaining the stability of the enzyme's quaternary structure. This structural feature explains its key function in the fatty acid β -oxidation pathway.

Fig. 1:Overview of recombinant HADH structure. Fig. 1 Overview of recombinant HADH structure.¹

Key structural properties of HADH:

Typical α/β fold three-domain structure
Conserved catalytic triplets constitute the active center
Rossmann folded conformation characteristic of the NAD+ coenzyme binding domain
Four dimer interface between salt bridge network to maintain structural stability

Functions of HADH

The core function of the protein encoded by the HADH gene is to catalyze the key step in the β -oxidation of fatty acids. This enzyme directly promotes the tricarboxylic acid cycle by specifically recognizing medium and short-chain hydroxyacyl-COA substrates and converting them into the corresponding ketoacyl-COA. Its functional system is specifically manifested as:

Function	Description
Energy metabolism-driven	Dehydrogenation of 3-hydroxyl-coa is catalyzed in the mitochondrial matrix to directly generate NADH, which provides an electron source for the respiratory chain.
Substrate channel regulation	Form metabolic channels with other subunits in the trifunctional protein complex to ensure efficient conversion of fatty acid oxidation intermediates.
Maintenance of metabolic homeostasis	By regulating the decomposition rate of medium and short-chain fatty acids, abnormal accumulation of lipid intermediates in the liver and heart muscle can be prevented.
Regulation of ketone body formation	Effect acetyl CoA flux, indirect intrahepatic ketone body to synthesize level adjustment.
Associated with congenital metabolic diseases	Enzyme activity deficiency leads to HADH deficiency, which is clinically manifested as hypoketogenic hypoglycemia and metabolic crisis like Rey's syndrome.

The catalytic kinetic characteristics of this enzyme are manifested as its specific recognition of the C4-C12 hydroxyacyl-COA substrate, and its reaction rate is regulated by the mitochondrial NAD+/NADH ratio. This regulatory mechanism ensures the energy supply switching under starvation conditions.

Applications of HADH and HADH Antibody in Literature

1. Ye, Haowen, et al. "HADH may be the target molecule of early vascular endothelial impairment in T2DM." Frontiers in Cardiovascular Medicine 9 (2022): 963916. https://doi.org/10.3389/fcvm.2022.963916

Through bioinformatics analysis, it was found that among the early vascular endothelial cell dysfunction caused by type 2 diabetes, the HADH gene has the highest diagnostic value. Experimental verification shows that HADH expression is significantly downregulated in human coronary endothelial cells treated with high glucose and palmitic acid, suggesting that it can serve as an early intervention target.

2. Shen, Congcong, et al. "Downregulation of HADH promotes gastric cancer progression via Akt signaling pathway." Oncotarget 8.44 (2017): 76279. https://doi.org/10.18632/oncotarget.19348

This study reveals for the first time that HADH inhibits tumor progression in gastric cancer by regulating the Akt signaling pathway. The expression of HADH in gastric cancer tissues decreases with the progression of the stage. Its down-regulation significantly promotes the migration and invasion of cancer cells, and this effect can be reversed by PI3K inhibitors.

3. Danquah, Bright D., et al. "Mass Spectrometric analysis of antibody—Epitope peptide complex dissociation: Theoretical concept and practical procedure of binding strength characterization." Molecules 25.20 (2020): 4776. https://doi.org/10.1109/JTEHM.2021.3104966

Studies have confirmed that HADH functional defects can disrupt the REDOX state of myocardial mitochondria. In the neonatal rat model, the REDOX ratio of the mutant heart was significantly reduced by 31.9%. This severe energy metabolism disorder is the key cause of heart failure and even sudden death.

4. Hashemian, Somayyeh, et al. "Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism." Case Reports in Endocrinology 2021.1 (2021): 8826174. https://doi.org/10.1155/2021/8826174

This study screened for pathogenic genes in children with congenital hyperinsulinemia. Among the 20 children patients, most of the variations were concentrated in the ABCC8 gene, and HADH is also an important pathogenic gene causing this disease, especially in the population with a high rate of consanguineous marriage, which requires special attention.

5. Çamtosun, Emine, et al. "A deep intronic HADH splicing mutation (c. 636+ 471G> T) in a congenital hyperinsulinemic hypoglycemia case: long term clinical course." Journal of clinical research in pediatric endocrinology 7.2 (2015): 144. https://doi.org/10.4274/jcrpe.1963

This study shows that the HADH gene defect is different from other fatty acid oxidation disorders. Its typical feature is hypoglycemia accompanied by hyperinsulinemia in neonates or infants. This article reports a case caused by a deep intron splicing mutation, presenting its long-term clinical course.

Creative Biolabs: HADH Antibodies for Research

Creative Biolabs specializes in the production of high-quality HADH antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom HADH Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our HADH antibodies, custom preparations, or technical support, contact us at email.

Reference

Reed, Timothy, et al. "Crystal structure of histamine dehydrogenase from Nocardioides simplex." Journal of Biological Chemistry 285.33 (2010): 25782-25791. https://doi.org/10.1074/jbc.M109.084301