Lecture 3

• Synthesis of Fatty acids occurs in liver, kidney,brain,lung,mammary gland and adipose tissue. In the cytoplasm
• Acetyl-CoA is the substrate, palmitate/fatty acid is the product. Fatty acid synthase is the enzyme. Intermediates are linked to ACP. NADPH,ATP,biotin are coenzymes
• Acetyl-CoA subunits are biotin carboxylase, carboxybiotin carrier protein, trans carboxylase
• Fatty acid oxidation uses thiolase. Fatty acid synthesis uses thioesterase
• The first enzyme is acety-CoA carboxylase. Which requires biotin
• Fatty acid synthase contains Vitamin B5 (phosphopanyhenol)
• Acety-CoA binds to SH of vitamin B5and removes CoA then shifts the acetyl to the cysteine group. Malony—CoA binds to vitamin B5 and the acetyl will take 2C from malonyl and become butyryl
• Sources of NADPH: pentose phosphate path (glucose-6-dehydrogenas and 6-phosphogluconate dehydrogenase), malic enzymes and isocitrate dehydrogenase
• Acetyl-CoA goes to sterols,fatty acids, TCA cycle, ketome bodies, protein acetylation
• Transport of acetyl-CoA

  
• Insulin activates citrate lyase
• citrate activates acetyl-CoA carboxylase and inhibitors are glucagon, adrenaline
• PalmitoylxCoA inhibits acetyl-CoA carboxylase
• When blood glucose is high Malonyl-CoA inhibits carnitine acyl-transferase 1 and oxidation is inhibited because no acetyl-CoA. When blood glucose is low synthesis of malonyl-CoA is inhibited
• Differences between oxidation and synthesis

  
• palmitate is changed to palmotoyl-CoA by acyl-CoA synthetase which is then used to from acly-CoA , acylglycerols, cholesterol esters
• Elongation of fatty acids occurs in the ER, and catalyzed by fatty acid elongase
• Synthesis of unsaturated fatty acids occur in the ER by ^9/4/5/6 desaturase
• Eicosanoids are derivatives of arachidonic acid. They act as local hormones. They consist of PG, TX, LT, LX
• Prostaglandins exist in all tissues, cause contraction and relaxtion of muscles, prevent contraceptio, asthma relief and nasal relief. Increase cAMP in the platelets, thyroid, corpus leuteum, fetal bone and lung. Reduce cAMP in renal tubule cells and adipose
• Prostacyclins produced by blood vessels and inhibit platelet aggregation
• Thromboxanes synthesized by platelets and cause vasoconstriction
• Leukotriened regulate inflamatory and hypersensitivit. Cause vascular permeability
• Lipoxins are vasoactive and immunoregulatory
• Activated phospholipase release econisamds and undergo lipoxygenase or cyclooxygenase
• Inhibitors of cyclooxygenase path: aspiri, salicylate, ibuprofen, naproxen, fluribiprofin (COX1) and celecoxib and rofecoxib (COX2)
• Lipoxygenase main enzyme
• Lecithins most abundant in cell membrane, large store of choline (nerve transmissions), surfactant (prevents adherence)
• Cephalons in cell membrane
• phosphatidylinositol precursors secondary messagers, cell membrane
• Lysophospholipids contain one acyl radical, intermediates of phosphoglycerok metabolism, lysolecithin or lysophosphatidylcholine important In metabolism and interconversion of phospholipids
• Cardiolipin in mitochondrial membrane
• Plasmalogens phospholipids in brain and muscle
• Sphingomyelins consist of fatty acid, phosphoric acid, choline, a complex amino alchol, sphingosine. In brain and nerve tissue
• Amphipathic lipids fatty acids, phospholipids, sphingolipids, bile acids and cholesterol contain polar groups. polar lipids in an aqueous solutions form micelles. the formation of biological membranes is based on the

  properties of lipids, forming a polar lipid bilayer
• Glycosphingolipids the major glycolipids found in animal tissues. they are widely distributed in every tissue of the body, particularly in nervous tissue such as brain. they occur particularly in the outer leaflet of the plasma membrane, where they contribute to cell surface carbohydrates
• Galactosylceramide major glycosphingolipid of brain and nervous tissue, contains C24 fatty acids
• Galactosylceramide can be converted to sulfa Galactosylceramide (high amounts in myelin)
• Glucosylceramide predominant simple glycosphingolipid of extraneural tissue and small amounts in brain
• Gangliosides derived from glucosylceramide and contain in addition on or more molecules of sialic acid, which principal is found in neuraminic acid in nervous tissue