Question

The starting point of beta-oxidation and the biosynthesis of phosphatidic acid and sphingolipids occurs in the cytosol with the activation of a fatty acid into a thioester. Briefly outline how these activated fatty acids are made. Be sure to describe the bioenergetics of the process.

Answer 1

Phosphatidic acid is a key intermediate metabolite for all membrane glycerophospholipids in their synthesis pathways. In addition to this metabolic contribution to biogenesis of membranes, phosphatidic acid is an essential signaling lipid particularly in the central nervous system. Phosphatidic acid may be formed by diacylglycerol phosphorylation, a reaction that is catalyzed by diacylglycerol kinase.

Diacylglycerol (DAG) is phosphorylated into phosphatidic acid (PA). In this reaction, the donor of phosphate is ATP.

The other possible pathway is the cleavage of membrane glycerophospholipids by phospholipase D.Total de novo synthesis of phosphatidic acid from dihydroxyacetone phosphate allows mammalian cells to counterbalance the conversion of phosphatidic acid into membrane glycerophospholipids.

Oxidation of the fatty acid is the mitochondrial aerobic process of breaking down a fatty acid into units of acetyl-CoA. In this pathway, fatty acids move as CoA derivatives which use NAD and FAD.

Until oxidation, fatty acids are activated using ATP in the presence of CoA-SH and synthetase with acyl-CoA. Long-chain acyl-CoA enteres carnitine-bound mitochondria.

Ceramide is the structural basis for all Sphingolipids. It has two hydrophobic groups and a polar alcohol which a polar head-group can be added to. So, we should speak of Diacylglycerol as equivalent to that.
The amine group that eventually forms the amide connection is provided by Serine. Most sphingolipids except sphingomyelin have a ceramide backbone, with at least one group of sugars connected to it.
Serine + Palmitoyl-CoA ------> ------> Ceramide

sphingolipids are glycosylated, there are almost always found on the exoplasmic side of the membrane. That means that they are synthesized on the luminal side of the ER membrane, and they are exported to the exoplasmic side of the plasma membrane. Sphingomyelin is simply a ceramide with Choline as its polar head-group.
Glycosylated sphingolipids are located almost exclusively at the exoplasmic side of the membrane. That means they are synthesized on the luminal side of the ER membrane, and exported to the plasma membrane's exoplasmic side. Sphingomyelin is essentially a ceramide with its polar head-group being Choline.

Phosphatidylcholine + Ceramide ——— > Diacylglycerol + Sphingomyelin

ENERGETICS OF beta-OXIDATION:

Only 2 ATP are invested.

-1 ATP is used for the Pyrophosphatase.

-1 ATP for the Acyl-CoA Ligase

We get below energy per turn of beta-Oxidation means per two carbons.

NADH +3 ATP

Acetyl-CoA +12 ATP

FADH2 +2 ATP

Total +17 ATP per 2 carbons.