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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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