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Lipid Metabolism Overview

  • Lipid metabolism encompasses the digestion, absorption, transportation, storage, and utilization of lipids in the body.

Digestion and Absorption of Lipids

Lipid Digestion - An Introduction

  • Dietary lipids: 98% triacylglycerols (TAGs), including fats and oils.

  • Salivary enzymes: ineffective on lipids (TAGs) as they are water insoluble.

  • Stomach processing: TAGs physically change into chyme (small globules) through a physical process, not chemical.

Lipid Digestion - The Stomach

  • Gastric lipase: hydrolyzes TAG ester bonds; about 10% of TAGs hydrolyzed.

  • High-fat meals prolong gastric retention, increasing satiety.

Lipid Digestion - The Intestinal Cells

  • Chyme enters the small intestine: emulsified by bile salts.

  • Pancreatic lipase: hydrolyzes TAGs; normally two out of three fatty acids are released.

  • Micelles formation: Fatty acids and monoacylglycerols combine with bile salts, allowing for absorption.

  • Repackaging: Monoacylglycerols and free fatty acids are converted back to TAGs in intestinal cells and packed into chylomicrons.

Lipid Digestion - Bloodstream

  • Hydrolysis in bloodstream: TAGs are fully hydrolyzed by lipase enzymes.

  • Fatty acids and glycerol: absorbed as energy (acetyl CoA) or stored as lipids.

Triacylglycerol Storage and Mobilization

Adipose Tissue Overview

  • Specialized storage: TAGs stored in adipocytes within adipose tissue.

  • Location: beneath the skin, abdominal region, around vital organs.

  • Function: insulation, protection, and energy storage.

Hydrolysis of TAGs

  • Hormonal triggers: cAMP activates hormone-sensitive lipase (HSL) leading to TAG breakdown.

  • Daily TAG replacement: Average replacement of 10%.

TAGs and Energy Reserves

  • Energy source: TAGs are the primary stored energy form, surpassing proteins and glycogen.

Glycerol Metabolism

Glycerol in Bloodstream

  • Conversion: Glycerol to dihydroxyacetone phosphate in liver/kidney via:

    1. Phosphorylation of glycerol.

    2. Oxidation to dihydroxyacetone phosphate.

Oxidation of Fatty Acids

Fatty Acid Breakdown

  • Three-step process:

    1. Activation by coenzyme A.

    2. Transport to mitochondrial matrix.

    3. Repeated oxidation to form acetyl CoA, FADH2, NADH.

Fatty Acid Activation

  • Occurs at the outer mitochondrial membrane; involves ATP conversion to AMP.

Fatty Acid Transport

  • Acyl CoA transported to mitochondrial matrix through a shuttle mechanism.

β-Oxidation Pathway Reactions

  • Four key reactions repeated to cleave two-carbon units:

    1. Dehydrogenation: Creates a double bond using FAD.

    2. Hydration: Forms a secondary alcohol.

    3. Second dehydrogenation: Oxidizes to a keto group using NAD+.

    4. Thiolysis: Cleaves the fatty acid chain to produce acetyl CoA.

Unsaturated Fatty Acids

Oxidation Process

  • Requires two extra steps compared to saturated fatty acids (epimerase and cis-trans isomerase).

ATP Production from Fatty Acid Oxidation

Energy Yield Overview

  • 120 net ATP synthesized from complete oxidation of C18 fatty acid (stearic acid), after accounting for activation costs.

  • Stearic acid produces 2.5 times more energy than glucose.

Ketone Bodies and Ketogenesis

Basic Concepts

  • Formation: Excess acetyl CoA from β-oxidation converted into ketone bodies under carbohydrate scarcity.

  • Conditions leading to ketogenesis: high-fat/low-carb diets, diabetes, prolonged fasting.

Key Ketone Bodies

  • Three main types produced: Acetoacetate, β-hydroxybutyrate, acetone.

Steps in Ketogenesis

  1. Acetyl CoA condenses to form acetoacetyl CoA.

  2. Condensation with a third acetyl CoA produces HMG-CoA.

  3. HMG-CoA is cleaved to acetyl CoA and acetoacetate.

  4. Acetoacetate can be reduced to β-hydroxybutyrate.

Lipogenesis

Overview of Fatty Acid Biosynthesis

  • Occurs in the cytosol, starting from Acetyl CoA transported via the citrate-malate shuttle.

  • ACP complex formation: Fatty acid synthesis intermediates linked to carrier proteins.

Chain Elongation Reactions

  • Involves condensation, reduction, dehydration, and re-addition of hydrogen.

Unsaturated Fatty Acid Production

  • Requires molecular O2; humans can introduce double bonds only at specific locations, necessitating dietary intake for some essential fatty acids.

Relationship Between Lipogenesis and the Citric Acid Cycle

  • Contrasts: Diacids in citric acid cycle vs. monoacids in lipogenesis; reverse order of reaction intermediates.

Fate of Acetyl CoA and Cholesterol Synthesis

Routes for Acetyl CoA

  • Acetyl CoA used for:

    • ATP production

    • Formation of ketone bodies

    • Storage as TAGs

    • Lipid and fatty acid production.

Role of Cholesterol

  • Critical for cell membranes & precursor for bile salts, sex hormones, adrenal hormones.

B Vitamins and Lipid Metabolism

Importance of B Vitamins

  • Act as coenzymes; important B vitamins include:

    • Niacin (NAD+/NADH/NADPH)

    • Riboflavin (FAD)

    • Pantothenic acid (CoA)

    • Biotin

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