Triacylglycerol Synthesis Fatty acyl-CoA DHAP reduction to glycerol-PO4 or Glycerol kinase to glycerol-PO4 Two esterifications Diacylglycerol-PO4 intermediate Triacylglycerol O-C-R O R-C-O

Triacylglycerol Biosynthesis glycolysis CH2OH CH2OP C=O NADH + NAD+ CH2OH HO-C-H CH2OP ADP ATP CH2OH HO-C-H glycerol kinase glycerol-PO4 dehydrogenase Not in adipose tissue DHAP Glycerol-PO4 R-C~CoA O 2 CH2O-C-R R-C-O-C-H CH2OP O Phosphatidic acid R-C~CoA O H2O PO4 CH2O-C-R R-C-O-C-H CH2OH O CH2O-C-R R-C-O-C-H O Phospholipid biosynthesis 1,2 Diacylglycerol (DAG)

Question Can a triacylglycerol (triglyceride) storage fat be synthesized entirely from glucose, i.e., every carbon in the fat comes from a sugar? Answer: YES

Glycerophospholipids CH2O-C-R R-C-O-C-H CH2OP O Phosphatidic Acid Phospholipid Biosynthesis (smooth ER) - or + O Ester linkage Polar component - or + = choline, serine, ethanolamine, etc Glycerophospholipids O CH2O-C-R R-C-O-C-H CH2OPO-CH2CH2-N(CH3)3 + Phosphatidylcholine or lecithin

Strategy of Glycerophospholipid Biosynthesis Activate diacylglycerol Activate appending moiety (salvage) Ribose PPP- CTP

Bacteria (Prokaryotes) Activate Phosphatidic acid Phosphatidic acid + CTP CDP-diacylglycerol + PPi CH2O-C-R R-C-O-C-H CH2OP~P-ribose-Cytosine O (CDP-diacylglycerol)

Bacteria (Prokaryotes) CDP-diacylglycerol Serine CMP Glycerol-PO4 CMP Phosphatidylserine Phosphatidylglycerol-3-PO4 Phosphatidyl- glycerol CO2 glycerol Phosphatidylethanolamine Cardiolipin Most prominent membrane lipid in bacteria Wassermann antigen for diagnosing syphilis

Eukaryotes 1 Glycerol 2 Glycerol-3-PO4 DHAP CH2O-C-R R-C-O-C-H CH2OP O ATP Glycerol 2 Glycerol-3-PO4 DHAP FA-CoA CH2O-C-R R-C-O-C-H CH2OP O 1-Acyl-DHAP Phosphatidic acid NADPH 3 DAG 1-Acyl-glycerol-3-PO4 ATP CTP CDP-diacylglycerol Pi ethanolamine (CDP-ethanolamine) CH2O-C-R R-C-O-C-H CH2OH O choline (CDP-choline) Serine (phosphatidylethanolamine) Glycerol (CDP-diacylglycerol) Inositol (CDP-diacylglycerol) 1,2 DAG Cardiolipin (phosphatidylglycerol)

N H N O O O N N C H C H O P O P O C H O O O H O C y t i d i n e d i p 2 N O O O N + H N C H C H O P O P O C H 2 2 3 2 O O O ethanolamine H O C y t i d i n e d i p h o s p h a t e ( C D P ) O H

SALVAGE Ethanolamine or choline HO-CH2-CH2-NH3+ ATP ADP Ethanolamine kinase or choline kinase O-CH2-CH2-NH3+ HO-P- O O- CTP PPi Phosphoethanolamine -P- O-CH2-CH2-NH3+ O-P- O O- Cytidine- DAG CMP CDP-ethanolamine Phosphatidylethanolamine Phosphatidylserine Serine Ethanolamine