Phosphatidylglycerol

Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant[1] and in the plasma membrane where it directly activates lipid-gated ion channels.

The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbone ester-bonded to either saturated or unsaturated fatty acids on carbons 1 and 2. The head group substituent glycerol is bonded through a phosphomonoester. It is the precursor of surfactant and its presence (>0.3) in the amniotic fluid of the newborn indicates fetal lung maturity.

Approximately 98% of alveolar wall surface area is due to the presence of type I cells, with type II cells producing pulmonary surfactant covering around 2% of the alveolar walls. Once surfactant is secreted by the type II cells, it must be spread over the remaining type I cellular surface area. Phosphatidylglycerol is thought to be important in spreading of surfactant over the Type I cellular surface area. The major surfactant deficiency in premature infants relates to the lack of phosphatidylglycerol, even though it comprises less than 5% of pulmonary surfactant phospholipids. It is synthesized by head group exchange of a phosphatidylcholine enriched phospholipid using the enzyme phospholipase D.


Biosynthesis

Phosphatidic acid reacts with CTP, producing CDP-diacylglycerol, with loss of pyrophosphate. Glycerol-3-phosphate reacts with CDP-diacylglycerol to form phosphatidylglycerol phosphate, while CMP is released. The phosphate group is hydrolysed forming phosphatidylglycerol. Phosphatidylglycerol combines with CDP-DAG forming cardiolipin releasing CMP by the action of cardiolipin synthase.

Two phosphatidylglycerols form cardiolipin, the constituent molecule of the mitochondrial inner membrane.[2] In eukaryotic mitochondria phosphatidylglycerol is converted to cardiolipin by reacting with a molecule of cytidine diphosphate diglyceride in a reaction catalyzed by cardiolipin synthase.[3]

See also
  • Glycerol
  • Cardiolipin
  • Lipid-gated ion channels

References
  1. Richard J. King; Mary Catherine MacBeth (6 October 1981). "Interaction of the lipid and protein components of pulmonarysurfactant Role of phosphatidylglycerol and calcium". Biochimica et Biophysica Acta (BBA) - Biomembranes. 647 (2): 159–168. doi:10.1016/0005-2736(81)90242-X. PMID 6895322.
  2. Ying-Ying Chang and Eugene P. Kennedy (September 1967). "Biosynthesis of phosphatidyl glycerophosphate in Escherichia coli". The Journal of Lipid Research. 8 (5): 447–455. doi:10.1016/S0022-2275(20)38901-X. PMID 4860577.
  3. Hostetler KY, van den Bosch H, van Deenen LL (March 1972). "The mechanism of cardiolipin biosynthesis in liver mitochondria". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 260 (3): 507–13. doi:10.1016/0005-2760(72)90065-3. hdl:1874/17621. PMID 4556770. S2CID 46101728.

3. Hostetler KY, van den Bosch H, van Deenen LL. The mechanism of cardiolipin biosynthesis in liver mitochondria. Biochim Biophys Acta. 1972 Mar 23;260(3):507-13. doi: 10.1016/0005-2760(72)90065-3. PMID: 4556770.

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