Dci

Official Full Name

enoyl-CoA delta isomerase 1

Synonyms

Dci;

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Detailed Information

Enoyl-CoA delta isomerase 1 (DCI) is an enzyme that plays a crucial role in lipid metabolism, specifically in the elongation of fatty acids.

Structure And Function of DCI

DCI is a member of the enoyl-CoA delta isomerase family, which is characterized by the conversion of unsaturated fatty acids to their cis-delta-unsaturated derivatives. The enzyme is composed of two distinct domains: the N-terminal domain, which is responsible for the binding of the enzyme to the lipid substrates, and the C-terminal domain, which contains the catalytic center.

The N-terminal domain of DCI is responsible for the recognition and binding of the substrate, which is a crucial step in the catalytic process. This domain is highly conserved across different species and contains several motifs that are characteristic of lipid binding proteins. These include a conserved glycine-rich motif, a hydrophobic pocket, and a leucine zipper-like motif.

The C-terminal domain of DCI contains the catalytic center, which is responsible for the conversion of the substrate to its product. This domain is also highly conserved across different species and contains several motifs that are characteristic of lipid metabolizing enzyme. These include a conserved serine-rich motif, a cysteine-rich motif, and a conserved acidic patch.

Regulation of DCI

The expression of DCI is regulated at multiple levels, including transcription, translation, and post-translational modification. The transcription of DCI is regulated by various transcription factors, including nuclear receptors, such as peroxisome proliferator-activated receptor alpha (Ppar-α) and liver X receptor alpha (LXRα). These transcription factors bind to the promoter region of the DCI gene and activate its transcription.

Post-translational modification of DCI includes phosphorylation, which is responsible for the activation or inactivation of the enzyme. For example, the activation of DCI by protein kinase C (PKC) leads to its translocation to the plasma membrane, where it is involved in the synthesis of eicosanoids. Additionally, the phosphorylation of DCI by protein kinase A (PKA) leads to its activation and increased catalytic activity.

Role of DCI in Lipid Metabolism

DCI plays a crucial role in lipid metabolism, specifically in the elongation of fatty acids. It is involved in the synthesis of eicosanoids, which are important signaling molecules that regulate various physiological processes, including inflammation, pain, and blood pressure. Additionally, DCI is involved in the synthesis of phospholipids, which are crucial for cell membrane structure and function.

DCI is a crucial enzyme involved in lipid metabolism, playing a significant role in the synthesis and breakdown of fatty acids and lipids. This enzyme participates in the final step of fatty acid synthesis, converting enoyl-CoA into 3-hydroxyacyl-CoA, which is essential for the production of triglycerides and other lipid molecules.

DCI And Disease

Mutations in the DCI gene can lead to defects in lipid metabolism, affecting various physiological processes including energy homeostasis, inflammation, and cell signaling. These mutations can result in abnormal lipid levels, contributing to the development of metabolic disorders such as obesity, diabetes, and atherosclerosis.

In obesity, mutations in the DCI gene can lead to impaired fatty acid synthesis and lipid accumulation, contributing to the excessive storage of fat in adipose tissue. This, in turn, can result in insulin resistance and the development of type 2 diabetes.

In atherosclerosis, mutations in DCI can affect lipid metabolism in vascular cells, leading to lipid accumulation in the arterial wall and promoting the development of atherosclerotic plaques. These mutations can also impair the clearance of atherogenic lipoproteins from the bloodstream, further exacerbating the disease process.

Furthermore, DCI has been implicated in inflammation and immune responses, as it serves as a regulatory enzyme in the synthesis of eicosanoids, a class of lipid mediators involved in inflammation and pain signaling. Mutations in DCI can lead to imbalances in eicosanoid production, contributing to chronic inflammation and autoimmune disorders.

References:

Goepfert, Simon et al. "Peroxisomal Delta(3),Delta(2)-enoyl CoA isomerases and evolution of cytosolic paralogues in embryophytes." The Plant journal: for cell and molecular biology vol. 56,5 (2008): 728-42. doi:10.1111/j.1365-313X.2008.03635.x
Patton, S M et al. "A novel delta(3),delta(2)-enoyl-CoA isomerase involved in the biosynthesis of the cyclohexanecarboxylic acid-derived moiety of the polyketide ansatrienin A." Biochemistry vol. 39,25 (2000): 7595-604. doi:10.1021/bi0005714

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