Page last updated: 2024-10-24

diacylglycerol biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of diacylglycerol, a glyceride in which any two of the R groups (positions not specified) are acyl groups while the remaining R group can be either H or an alkyl group. [GOC:curators]

Diacylglycerol (DAG) biosynthesis is a crucial metabolic pathway that plays a pivotal role in cellular signaling, membrane lipid homeostasis, and various physiological processes. DAG is a key signaling molecule that activates protein kinase C (PKC), a family of serine/threonine kinases involved in diverse cellular processes. DAG biosynthesis is tightly regulated and involves a series of enzymatic reactions that utilize various substrates and intermediates. The primary pathway for DAG synthesis involves the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme phospholipase C (PLC), generating DAG and inositol triphosphate (IP3). PLC can be activated by a variety of extracellular signals, including hormones, neurotransmitters, and growth factors. Another major pathway for DAG synthesis is the de novo pathway, which involves the acylation of glycerol-3-phosphate (G3P) by two acyl-CoA molecules. This pathway is catalyzed by two enzymes: glycerol-3-phosphate acyltransferase (GPAT) and 1-acylglycerol-3-phosphate acyltransferase (AGPAT). The first acylation step generates lysophosphatidic acid (LPA), which is then further acylated by AGPAT to form DAG. Additionally, DAG can also be generated through the breakdown of phospholipids by phospholipases A2 (PLA2), which remove fatty acids from the sn-2 position of phospholipids. DAG production is tightly regulated by various mechanisms, including feedback inhibition by DAG itself and regulation by enzymes involved in its synthesis and breakdown. Diacylglycerol kinases (DGKs) convert DAG to phosphatidic acid (PA), a key precursor for phospholipid biosynthesis. DAG is also a precursor for triacylglycerol (TAG) biosynthesis, a major energy storage molecule. The diverse roles of DAG in cellular signaling and metabolism highlight its significance in maintaining cellular function and homeostasis. '
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Proteins (2)

ProteinDefinitionTaxonomy
Diacylglycerol O-acyltransferase 2A diacylglycerol O-acyltransferase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96PD7]Homo sapiens (human)
Patatin-like phospholipase domain-containing protein 2A patatin-like phospholipase domain-containing protein 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96AD5]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
azd7687AZD7687: structure in first source
pf-04620110PF-04620110: a DGAT1 inhibitor; structure in first source
atglistatinatglistatin : A biphenyl that is 1,1'-biphenyl substituted by (dimethylcarbamoyl)amino and dimethylamino groups at positions 3 and 4', respectively. It is a potent inhibitor of adipose triglyceride lipase activity (IC50 = 700nM).

atglistatin: inhibits adipose triglyceride lipase; structure in first source
pf-06424439PF-06424439: an inhibitor of diacylglycerol acyltransferase 2; structure in first source