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Transcript
COMPLEX LIPIDS
DENTAL BIOCHEMISTRY 2015
Lecture 18
Michael Lea
COMPLEX LIPIDS - LECTURE OUTLINE
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Triglyceride synthesis
Synthesis of phosphatidyl compounds
Phospholipases
Synthesis of sphingolipids
Degradation of sphingolipids and
sphingolipidoses
• Suggested reading: Lippincott’s Biochemistry 6th
edition, pages 181, 188-189, 201-212
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).
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.
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
(dihydrosphingosine)
Sphingomyelin
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 TaySachs disease.
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.