1. COMPLEX LIPIDS DENTAL BIOCHEMISTRY 2015 Lecture 18 Michael Lea

2. COMPLEX LIPIDS - LECTURE OUTLINE Triglyceride synthesis Synthesis of phosphatidyl compounds Phospholipases Synthesis of sphingolipids Degradation of sphingolipids and sphingolipidoses Suggested reading: Lippincott’s Biochemistry 6 th edition, pages 181, 188-189, 201-212

3. TRIGLYCERIDE SYNTHESIS Two fatty acids are transferred from fatty acyl coenzyme A molecules to glycerol 3-phosphate to yield a phosphatidic acid. The phosphate group is hydrolyzed. A third fatty acyl group is added to yield a triglyceride (triacylglycerol).

4. TRIGLYCERIDE SYNTHESIS In adipocytes, glycerol 3-phosphate can be formed by the reduction of dihydroxyacetone phosphate catalyzed by glycerol-3-phosphate dehydrogenase In liver, glycerol kinase catalyzes the phosphorylation of glycerol to form glycerol 3-phosphate.

6. PHOSPHATIDYL COMPOUNDS There are two types of mechanism for the formation of phosphatidyl compounds that consist of a phosphatidyl group attached to a polar head group. These mechanisms involve activation of either the phosphatidyl group or the head group with CDP. In the case of phosphatidyl choline (lecithin) there is the intermediate formation of CDP-choline. Phospholipases selectively hydrolyze specific ester linkages on phosphatidyl compounds

9. (dihydrosphingosine)

10. Sphingomyelin

13. SPHINGOLIPIDS The molecule sphingosine is synthesized from palmitoyl coenzyme A and the amino acid serine. Acylation with a fatty acid transferred from a fatty acyl coenzyme A results in the formation of a ceramide. Addition of choline phosphate yields sphingomyelin while the addition of sugars yields cerebrosides and globosides. Those glycolipids that contain sialic acid are known as gangliosides. The sphingolipids are important molecules in cell membranes and are particularly rich in nerve tissue. Hereditary defects in hydrolases required for the degradation of these molecules result in their accumulation and frequently involve neurological impairment as in Tay- Sachs disease.

17. COMPLEX LIPIDS - LECTURE OBJECTIVES After completing this unit you should be able to 1. describe the composition of triglycerides and complex phospho- and glycolipids. 2. show how diacylglycerol serves as an intermediate in more than one pathway of lipid synthesis. 3. contrast different strategies used in the synthesis of phosphatidyl compounds. 4. identify the action of different phospholipases. 5. distinguish the composition of different sphingolipids. 6. explain how specific enzyme deficiencies can result in the inborn errors of metabolism known as sphingolipidoses.