Dr. Lucie Škarydová, Ph.D.

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A group of heterogenous substances Insolubility in water! The importance of lipids:
◦ Source of energy ◦ Products of lipid metabolism – important substrates for other metabolic pathways! ◦ A part of biomembranes – cytoplazmatic m., subcellular membranes ◦ Precursors of vitamins, hormones

6. 2. regulation Fatty acids – degradation. 7.1. synthesis. Triacylglycerols – degradation. 5. 3. 4. regulation Complex lipids Cholestrol – biosynthesis. regulation Ketone bodies Fatty acids – biosynthesis. regulation Review of lipids .

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  TAG = triglycerides. neutral lipids Esters of a glycerol and fatty acids .

 The major source of energy for the body ◦ Provide twice more energy than other nutrients Δ H. kJ/g of dry basis carbohydrate lipid protein 16 37 17  Adipose tissue ◦ Adipocytes .

also PL. cholesterol) Digestion of lipids (lectures in physiology!) ◦ Mainly in a small intestine ◦ Duodenum  Emulsification (bile acids from gallblader)  micelles  Pancreatic lipase ◦ Jejunum – absorption ◦ Transport to tissues – chylomicrons  Lipoprotein lipase in capillaries  Tissues – storage x utilization! .  Dietary lipids (mainly TAG.

 Mobilization of stored fats o a fasting. adaptation to a stress Hormone-sensitive lipase (HSL) • o Hydrolysis of TAG in adipose tissue – release of glycerol + fatty acids to blood Important – adaptation to stress!!! Epinephrine and glucagon – increase of HSL activity! • • . intensive physical exercise.

glucagon . The activation of HSL by hormones ◦ Epinephrine. activity. activity . insulin .

kidney! low activity in adipose tissue o Glycerol – a source of glucose during fasting! .o Fatty acids – a source of energy mainly for myocardium and muscles Liv er.

 Synthesis of TAG ◦ ◦ ◦ Predominantly in liver and adipose tissue Glycerol-3-phosphate (dihydroxyaceton phosphate) Activated fatty acids (acyl-CoA) ◦ Glycerol phosphate in adipose tissue – only from glucose (low activity of glycerol kinase)! .

activation of lipolysis  High concetration of free fatty acids in blood ◦ Hormones   Insulin – activation of phosphodiesterase . glucagon – activation HSL . lipogenesis Epinephrine.activity . food with high TAG – inhibition of lipogenesis. fatty acids in blood . lipolysis . Regulation of TAG metabolism ◦ Nutrition state of organism  Good supply of food – utilization of glucose   lipogenesis (fat storage)  Low concentration of free fatty acids in blood  Fasting. cAMP – dephosphorylation of HSL .

 Summary of TAG: Esters of a glycerol and fatty acids o Major source of energy in organism o The main type of fat in food o Hormone-sensitive lipase – adaptation to stress!!! o o Metabolism of lipids is affected by nutrition state of organism and hormones! .

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  Mainly in the form of esters Even number of C (mainly 16-20 C) ◦ Saturated FA – without double bonds ◦ Unsaturated FA – double bonds – cis conformation!  Stearic acid (18:0) • Palmitooleic acid (16:1(9)) .

 Essential FA – linoleic a. α-linolenic a..8.11. leukotriens and tromboxans (inflammatory mediators) . ◦ Inability to synthesize them – supply from food!  Arachidonic acid 20:4 (5.14)  prostaglandins.

 Oxidation of fatty acids o The main catabolic route of FA • • • Progressive elimination of two carbon fragments from FA Products . FADH2.acetyl-CoA . NADH+H+ Production of a high amount of ATP o Mitochondrial pathway Only in the presence of O2 Consist of several steps: • • • o o Activation of FA Transport of FA to mitochondria β-oxidation of FA .

 Activation of fatty acids o o Take place in cytosol Delivery of energy (ATP) is required!!! o Both high-energy ATP bonds are utilized! .

 Transport of FA to mitochondrial matrix o Inner membrane is impermeable for Acyl-CoA  specialized carrier is required – carnitine o Carnitine obtained from diet (mainly meat product) and synthetized in the body .

 Steps of translocation .

 ◦ ◦ β-oxidation Occurs in mitochondrial matrix Cyclic repetition of 4 reactions:     Dehydrogenation (FAD) – a double bond formation Hydratation of the double bond – 3-L-hydroxyacyl-CoA Dehydrogenation (NAD+) – β-ketoacyl-CoA Thiolysis – cleavage of the bond between Cα-Cβ ◦ One cycle – 2C shortening of acyl chain  Acetyl-CoA molecule is formed in every cycle .

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NADH+H+ – respiratory chain – 2.  Oxidation of FA – high energy yield! Every cycle – FADH2. acetyl-CoA ◦ ◦ FADH2. NADH+H+. 3 ATP Acetyl-CoA – citric acid cycle – 12 ATP 2 ATP for activation  Total oxidation of palmitoic acid (16C) ◦ .

 Oxidation of FA with an even number of C ◦ Products – acetyl-CoA Products – acetyl-CoA + propionyl-CoA (3C) O CO2 ATP ADP+Pi  Oxidation of FA with an odd number of C ◦ H OOC C CH3 (S)-metylmalonyl-COA O C SCoA metylmalonyl CoA racemase H O C - H3C CH2 C SCoA propionyl CoA carboxylase - H3C C SCoA propionyl-CoA COO (R)-metylmalonyl-CoA methylmalonyl mutase O - OOC CH2 C SCoA sukcinyl-CoA citric acid cycle .

 Special types of β-oxidation ◦ β-oxidation of unsaturated FA – modified   Provides less energy Normal β-oxidation to a double bond  isomerization of cis to trans configuration  normal β-oxidation ◦ Peroxizomal β-oxidation    Very-long-chain FA (> 22C) Shortened in peroxisomes (to octanoyl-CoA) Diffusion to mitochondial matrix  normal β-oxidation  Exist also α.and ω-oxidation of FA – rare! .

 Regulation of β-oxidation ◦ Hormone-sensitive lipase (HSL)     ◦ Delivery of substrates Degradation of TAG v adipocytes  release of MK  epinephrine. glucagon – adaptation to stress  insulin Low activity after food Inhibition of high concentration of malonyl-CoA – an indicator of the FA synthesis in cytosol Inhibition of  acetyl-CoA Carnitine acyltransferase I   ◦ Thiolase  .

bile acids . vitamins. The fate of acetyl-CoA in the organism ◦ Source of energy   Physiological conditions – citric acid cycle Excess (fasting. diabetes mellitus) – ketone bodies ◦ Precursor   FA  TAG. complex lipids Cholesterol  steroid hormones.

transport.acetyl-CoA. NADH+H+ o o Significance:   Energy Product acetyl-CoA – an important substrate for other metabolic route . Summary of degradation of FA: Oxidation of FA consist of 3 steps – activation. FADH2. β-oxidation o β-oxidation – a cyclic repetition of 4 steps o Products .

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water soluble equivalents of FA .  An alternative fuel for cells Ketogenesis – conversion acetyl-CoA (product of FA oxidation) to ketone bodies   Produced in liver mitochondia Ketone bodies .

during fasting  Fasting  ketone bodies are an important source of energy for tissues (also brain)!!! . Why ketone bodies are produced? ◦ Acetyl-CoA   Citric acid cycle Ketogenesis  Green .

acetoacetate spontaneously 3-hydroxybutyrate dehydrogenase O H3C C CH3 acetone 3-hydroxybutyrate . Synthesis of ketone bodies ◦ 2x acetyl CoA thiolase Only in liver mitochondria H3C CoASH O O C CH2 C H2O SCoA acetacetyl-CoA HMG CoA synthase acetyl CoA CoAsH OH - O CH2 OOC CH2 C CH3 C SCoA 3-hydroxy 3-metylglutaryl-CoA (HMG-CoA) HMG CoA lyase acetyl-CoA O H3C NADH+H ++ NAD+ H H3C C OH CH2 COO - C CH2 COO.

diabettes mellitus) . Utilization of ketone bodies  Ketone bodies are acids   production  acidosis (typical state .

aceton. 3-hydroxybutyrate Important source of energy during fasting   ◦ Peripheral tissues – utilization in citric acid cycle Hard fasting – source of energy for brain (physiological source of energy – only glucose!) ◦ Ketoacidosis – typical for diabettes mellitus . Summary of ketone bodies ◦ Acetoacetate.

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