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04/21/23 11:02 1
LIPID LIPID METABOLISMMETABOLISM
December 2007December 2007
Monogastric DigestionChallenges
1.Lipids are not water soluble2.Triglycerides too large to be absorbed
Digestive solution1.Triglycerides mix with bile and pancreatic
secretions2.Emulsification and digestion
BileProduced in liver, stored in gallbladder
Except horseAlkaline solution composed of:
Bile saltsCholesterolLecithinBilirubin
Responsible for fat emulsificationDetergent action
Mixed micelle formed by bile salts, triacylglycerols and pancreatic lipase.
Digestion of LipidBile salts emulsify lipidsPancreatic lipase acts on triglycerides
Triglycerides sn-2 monoglyceride + 2 fatty acids
Pancreatic colipaseActivated by trypsinInteracts with triglyceride and pancreatic
lipase Displaces bile to allow recycling Improves activity of pancreatic lipase
Pancreatic Colipase
Secreted from pancreas as procolipase
Activated (cleaved) by trypsin
Anchors lipase to the micelle
One colipase to one lipase(i.e., 1:1 ratio)
EmulsificationProduces small lipid spheres
Greater surface areaLipases attack TG at 1 and 3 positionsGlycerol
Fatty Acid1
Fatty Acid2
Fatty Acid3
Lipase
Glycerol
Fatty Acid3
Fatty Acid1Fatty
Acid2
Triglyceride 2-Monoglyceride
+
2 Free Fatty Acids
2 H20
Digestion of LipidPhospholipase A1 and A2
Hydrolyzes fatty acids from phospholipidsCholesterol esterase
Hydrolyzes fatty acids from cholesterol esters
Micelle FormationComplex of lipid materials soluble in waterContains bile salts, phospholipids &
cholesterolCombines with 2-monoglycerides, free
fatty acids and fat-soluble vitamins to form mixed micelles
Micelle Formation
Lipid Absorption
Short and medium chain fatty acids
simple diffusion exocytosis
Overview of Fatty Acid UptakeShort- and medium-chain fatty acids
Enter portal blood directly from enterocytesBound to albumin in blood
Albumin–FFA complexOxidized in liver or elongated and used for
triglyceride formationLong-chain fatty acids
Form chylomicronsDrain into the lymphatics via the lacteal in
mammals (no lacteal in avian small intestinal villi)
Enter bloodstream at the thoracic duct Upstream from liver Slow entry into the blood
Overview of Lipid Digestion in Mammals
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Fatty Acids Fatty Acids ββ-Oxidation-Oxidation
Fatty Acids Beta OxidationFatty Acids Beta Oxidation
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Fatty Acid Translocation into MitochondrionFatty Acid Translocation into Mitochondrion
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Stages of Fatty Acids Beta OxidationStages of Fatty Acids Beta Oxidation
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β - Oxidation Fatty Acids (with odd carbon number)
β - Oxidation Fatty Acids (Peroxisomes)
α - Oxidation Fatty Acids
ω - Oxidation Fatty Acids
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Odd Chain Fatty Acids Odd Chain Fatty Acids Beta OxidationBeta Oxidation
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Unsaturated Fatty Acids Unsaturated Fatty Acids Beta OxidationBeta Oxidation
Linoleic acid (18:2)
cis-9, trans-11 CLA
trans-11 18:1
Stearic acid (18:0)
isomerase
reductase
reductase
Intermediate fatty acids are conjugated linoleic acids
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Regulation of Beta Regulation of Beta OxidationOxidation
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Carnitine DeficiencyCarnitine DeficiencyCPT-I and CPT-II DeficiencyCPT-I and CPT-II DeficiencySulfonylurea Drug ConsumptionSulfonylurea Drug ConsumptionJamacaican Vomitting SicknessJamacaican Vomitting SicknessDicarboxylic AciduriaDicarboxylic AciduriaRefsum's DiseaseRefsum's DiseaseZellweger‘s DiseaseZellweger‘s Disease
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Regulation of Regulation of KetogenesisKetogenesis
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CLINICAL ASPECTSCLINICAL ASPECTS
Impaired Oxidation of Fatty Acids Gives Rise to Diseases Often Associated With Hypoglycemia
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Fatty Acid SynthesisFatty Acid Synthesis(Lipogenesis)(Lipogenesis)
Fatty acid synthase complexFatty acid synthase complex
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Methyl malonyl-CoA BiosynthesisMethyl malonyl-CoA Biosynthesis
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Fatty acid synthesis: stage-1Fatty acid synthesis: stage-1
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Fatty acid synthesis: stage-2Fatty acid synthesis: stage-2
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Fatty acid synthesis: stage-3Fatty acid synthesis: stage-3
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Fatty acid synthesis: stage-4Fatty acid synthesis: stage-4
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Fatty acid synthesis: stage-5Fatty acid synthesis: stage-5
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FA Elongation SystemER ( microzomes) is the local of EFAElangase Enzyme System
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Acety CoAAcety CoA transportion transportion and and NADPHNADPH production production PathwaysPathways
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Regulation of LipogenesisRegulation of Lipogenesis
Nutritional StateNutritional StateCarbohydrate or Lipid IntakeCarbohydrate or Lipid IntakeRegulation of Acetyl-CoA CarboxylaseRegulation of Acetyl-CoA CarboxylaseRegulation of Pyruvate DehydrogenaseRegulation of Pyruvate DehydrogenaseEffect of HormoneEffect of Hormone
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Unsaturated fatty acid BiosynthesisOne unsaturated FA; Liver is the position synthesis The first local is the position Δ9
Δ9 Desaturase enzyme system in ER ( O2 + NADPH+ Cytochrome b5)
Poly unsaturated FA;
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