CDP-diacylglycerol biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of CDP-diacylglycerol, CDP-1,2-diacylglycerol, a substance composed of diacylglycerol in glycosidic linkage with cytidine diphosphate. [PMID:24533860]

CDP-diacylglycerol (CDP-DAG) biosynthesis is a crucial metabolic pathway responsible for the production of CDP-DAG, a key precursor molecule involved in the synthesis of various essential membrane lipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin. The process can be broadly divided into two distinct steps:

1. **Diacylglycerol (DAG) Formation:** The pathway begins with the activation of glycerol-3-phosphate (G3P) by phosphorylation to form glycerol-3-phosphate (G3P). This phosphorylation is catalyzed by the enzyme glycerol-3-phosphate kinase. Subsequently, two fatty acyl chains are esterified to G3P, generating lysophosphatidic acid (LPA). The addition of the second fatty acyl chain is catalyzed by lysophosphatidic acid acyltransferase (LPAAT), which utilizes fatty acyl-CoA as a substrate. This results in the formation of diacylglycerol (DAG), a pivotal intermediate in the CDP-DAG biosynthetic pathway.

2. **CDP-DAG Formation:** DAG undergoes activation by phosphorylation using cytidine triphosphate (CTP) as the phosphate donor. This reaction is catalyzed by the enzyme CDP-diacylglycerol synthase (CDS), leading to the formation of CDP-diacylglycerol (CDP-DAG).

The resulting CDP-DAG molecule serves as a critical precursor for the biosynthesis of various membrane lipids. For instance, CDP-DAG reacts with glycerol-3-phosphate to form phosphatidylglycerol (PG) through the action of phosphatidylglycerophosphate synthase. Similarly, CDP-DAG reacts with inositol to produce phosphatidylinositol (PI) under the catalysis of phosphatidylinositol synthase. Notably, cardiolipin, a unique phospholipid found primarily in the inner mitochondrial membrane, is synthesized via the condensation of two CDP-DAG molecules, catalyzed by cardiolipin synthase.

The CDP-DAG biosynthetic pathway is highly regulated to ensure optimal lipid production and maintain membrane integrity. Regulatory mechanisms include substrate availability, enzyme activity, and feedback inhibition by product molecules. Furthermore, mutations in genes encoding enzymes involved in CDP-DAG biosynthesis can lead to various human diseases, including lipid storage disorders and metabolic syndromes.
'"

Proteins (1)

Compounds (2)