Target type: biologicalprocess
The chemical reactions and pathways resulting in the formation of cardiolipin, 1,3-bis(3-phosphatidyl)glycerol. [GOC:mah]
Cardiolipin biosynthesis is a complex process that involves multiple enzymes and steps, ultimately leading to the synthesis of cardiolipin, a unique phospholipid found predominantly in the inner mitochondrial membrane.
**Step 1: Synthesis of phosphatidic acid (PA)**
* The process begins with the activation of glycerol by glycerol-3-phosphate acyltransferase (GPAT) to form glycerol-3-phosphate.
* Glycerol-3-phosphate is then acylated by acyl-CoA synthetases (ACS) to form lysophosphatidic acid (LPA).
* Finally, LPA is further acylated by lysophosphatidic acid acyltransferase (LPAAT) to generate phosphatidic acid (PA).
**Step 2: Synthesis of CDP-diacylglycerol (CDP-DAG)**
* PA is converted to CDP-diacylglycerol (CDP-DAG) by the enzyme phosphatidic acid cytidylyltransferase (CPT1). This step involves the attachment of cytidine diphosphate (CDP) to the phosphate group of PA.
**Step 3: Synthesis of phosphatidylglycerol (PG)**
* CDP-DAG reacts with glycerol-3-phosphate, catalyzed by phosphatidylglycerophosphate synthase (PGPS), to form phosphatidylglycerophosphate (PGP).
* PGP is then dephosphorylated by phosphatidylglycerophosphate phosphatase (PGPP) to yield phosphatidylglycerol (PG).
**Step 4: Synthesis of cardiolipin (CL)**
* The final step in cardiolipin biosynthesis involves the condensation of two molecules of CDP-DAG with one molecule of PG, catalyzed by cardiolipin synthase (CLS). This reaction results in the formation of cardiolipin, a molecule containing four fatty acyl chains and three glycerol moieties.
**Regulation of Cardiolipin Biosynthesis**
* Cardiolipin biosynthesis is tightly regulated to ensure the proper function of mitochondria.
* Regulation occurs at multiple levels, including the availability of substrates, the activity of enzymes, and the expression of genes involved in cardiolipin biosynthesis.
**Role of Cardiolipin**
* Cardiolipin is a crucial component of the inner mitochondrial membrane and plays a critical role in various cellular processes, including:
* **Electron transport chain:** Cardiolipin interacts with and stabilizes respiratory chain complexes, contributing to efficient electron transport.
* **Mitochondrial membrane dynamics:** It helps maintain the structural integrity and fluidity of the inner mitochondrial membrane.
* **Apoptosis:** Cardiolipin is involved in the apoptotic process, acting as a signaling molecule.
* **Mitochondrial protein import:** It plays a role in the import of proteins into the mitochondrial matrix.
Defects in cardiolipin biosynthesis or its metabolism can lead to various mitochondrial disorders, affecting energy production, cellular signaling, and overall cellular function.'
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Protein | Definition | Taxonomy |
---|---|---|
85/88 kDa calcium-independent phospholipase A2 | An 85/88 kDa calcium-independent phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60733] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
3-octylthio-1,1,1-trifluoro-2-propanone | 3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase | ||
varespladib | aromatic ether; benzenes; dicarboxylic acid monoamide; indoles; monocarboxylic acid; primary carboxamide | anti-inflammatory drug; antidote; EC 3.1.1.4 (phospholipase A2) inhibitor |