Metabolism of lipids - exercise - Vladimíra Kvasnicová Choose compounds counting among lipids a) fatty acids and glycerol b) triacylglycerols and phospholipids c) ketone bodies d) cholesterol Choose compounds counting among lipids a) fatty acids and glycerol b) TAG and phospholipids c) ketone bodies d) cholesterol Aceton The fiugure is from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2 Free Fatty Acids = FFA a hydrophobic hydrocarbon sceleton predominates The figure is found at http://www.tvdsb.on.ca/saunders/courses/online/SBI3C/Cells/Lipids.htm (Jan 2007) a hydrophobic hydrocarbon sceleton predominates The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads2/ch11_cholesterol.jpg (Jan 2007) Lipoproteins contain a) a phospholipid bilayer on their surface b) free cholesterol in their core c) triacylglycerols in their core d) surface proteins having a role of ligands, which can bind to receptors of target cells Lipoproteins contain a) a phospholipid bilayer on their surface b) free cholesterol in their core c) triacylglycerols in their core d) surface proteins having a role of ligands, which can bind to receptors of target cells other functions: apoproteins activate enzymes metabolizing lipoproteins, or they have a structural function lipids are transported in a form of lipoproteins in blood The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. Choose correct statements about a transport of lipids in blood a) triacylglycerols are transfered mainly by chylomicrons and VLDL b) free fatty acids are bound to albumin c) cholesterol is transfered mainly by HDL and LDL d) ketone bodies do not need a transport protein Choose correct statements about a transport of lipids in blood a) triacylglycerols are transfered mainly by chylomicrons and VLDL b) free fatty acids are bound to albumin c) cholesterol is transfered mainly by HDL and LDL d) ketone bodies do not need a transport protein The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990. Releasing of free fatty acids from TAG of fatty tissue and their followed transport to target cells The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/o verheads-3/ch17_lipid-adipocytes.jpg (Jan 2007) Choose correct statements about properties of lipoproteins a) chylomicrons are formed in enterocytes b) VLDL conteins the apoC-II - an activator of a lipoprotein lipase c) apoproteins A (apoA) are specific for LDL d) HDL transfers cholesterol from the liver to extrahepatic tissues Choose correct statements about properties of lipoproteins a) chylomicrons are formed in enterocytes b) VLDL conteins the apoC-II - an activator of a lipoprotein lipase c) apoproteins A (apoA) are specific for LDL d) HDL transfers cholesterol from the liver to extrahepatic tissues Lipoproteins type source principal lipids important apoproteins they transport: chylomicrons intestine TAG B-48, C-II, E TAG from a diet to various tissues CHM remnants chylomicrons (CHM) cholesterol, TAG, phospholipids B-48, E remnants of chylomicrons to the liver VLDL liver TAG C-II, B-100 newly synthetized TAG to other tissues IDL VLDL cholesterol, TAG, phospholip. B-100 VLDL remnants to other tissues LDL VLDL cholesterol B-100 cholesterol to extrahepat. tissues HDL liver cholesterol, A-I, E, C-II cholesterol from phospholipids, tissues back to the store of apoprot. liver Lipases a) catalyze cleavage of fatty acids b) catalyze cleavage of cholesterol esters c) are found on the inner surface of blood vessels d) are found in the adipose tissue Lipases a) catalyze cleavage of fatty acids b) catalyze cleavage of cholesterol esters c) are found on the inner surface of blood vessels = lipoprotein lipase d) are found in the adipose tissue = hormone sensitive lipase Lipases name source location of its action function properties acid stable lipase stomach stomach hydrolysis of TAG composed of short chain fatty acids stability in low pH pancreatic lipase pancreas small intestine hydrolysis of TAG to 2 fatty acids and 2-monoacylglycerol needs pancreatic colipase lipoprotein lipase extrahepatic tissues inner surface of blood vessels hydrolysis of TAG found in VLDL and chylomicrons activated by apoC-II hormon sensitive lipase adipocytes cytoplasm of adipocytes hydrolysis of reserve triacylglycerols activated by phosphorylation acidic lipase various tissues lysosomes hydrolysis of TAG acidic pHoptimum Regulation of lipolysis regulatory enzyme activation hormone sensitive lipase (in adipocytes) catecholamines, glucagon (phosphorylation) lipoprotein lipase (inner surface of blood vessels) insulin apolipoprotein C-II (apoC-II) inhibition insulin prostaglandins Fatty acids a) can contain double bonds b) are found in the fatty tissue in their esterified form c) are found in membrane phospholipids d) can be converted to ketone bodies Fatty acids a) can contain double bonds b) are found in the fatty tissue in their esterified form as triacylglycerols (TAG) c) are found in membrane phospholipids d) can be converted to ketone bodies -oxidation of fatty acids a) proceeds in a mitochondrion b) produces oxidized forms of coenzymes c) proceeds in a nervous tissue as well d) is regulated on the level of FFA transport into the mitochondrion -oxidation of fatty acids a) proceeds in a mitochondrion b) produces oxidized forms of coenzymes c) proceeds in a nervous tissue as well d) is regulated on the level of FFA transport into the mitochondrion carnitine transporter -oxidation of fatty acids (1 cycle) The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007) Carnitine acyltransferase a) is activated by malonyl-CoA b) transfers the molecule of acyl-CoA into the mitochondrion c) transfers acyls of the maximal length of 18 carbons d) transfers carnitin out of the mitoch. matrix Carnitine acyltransferase a) is activated by malonyl-CoA b) transfers the molecule of acyl-CoA into the mitochondrion c) transfers acyls of the maximal length of 18 carbons d) transfers carnitin out of the mitoch. matrix regulatory enzyme carnitin palmitoyltransferase I (carnitin acyltransferase) activation inhibition malonyl-CoA (= intermediate of FA synthesis) cytoplasm Transport of fatty acids into a mitochondrion CARNITINE TRANSPORTER The figure was adopted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2 Acetyl-CoA generated by -oxidation can be a) oxidized in a citrate cycle b) transformed to ketone bodies c) transformed to glucose d) used in a cholesterol synthesis Acetyl-CoA generated by -oxidation can be a) oxidized in a citrate cycle b) transformed to ketone bodies c) transformed to glucose !!! d) used in a cholesterol synthesis Acetyl-CoA can not be converted to pyruvate: pyruvate dehydrogenase reaction is irreversible. Ketone bodies a) can be used as an energy substrate for the liver b) are formed in various tissues c) can be transformed to glucose d) can be oxidized to CO2 and water Ketone bodies a) can be used as an energy substrate for the liver b) are formed in various tissues c) can be transformed to glucose !!! d) can be oxidized to CO2 and water Ketone bodies synthesis (= ketogenesis) • proceeds if -oxidation is • ounly in the liver: mitochondria Acetyl-CoA OH The figure is found at http://en.wikipedia.org/wiki/Image:Ketogenesis.png (Jan 2007) Regulation of ketogenesis regulatory enzyme activation inhibition hormon sensitive ratio ratio lipase glucagon / insulin insulin / glucagon (lipolysis in fatty catecholamines tissue) carnitine malonyl-Co A acyltransferase I ratio (transfer of fatty insulin / glucagon acids into mitochondria) Ketone bodies degradation (oxidation) proceeds during starvation in extrahepatic tissues as an alternative energy source (in a brain as well) Citrate cycle The figure is found at http://www.richmond.edu/~jbell2/19F18.JPG (Jan 2007) Fatty acid synthesis a) proceeds in a mitochondrion b) starts by the reaction: acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA c) needs NADPH+H+ as a coenzyme d) includes the reaction order: dehydrogenation, hydration, dehydrogenation, cleavage Fatty acid synthesis a) proceeds in a mitochondrion b) starts by the reaction: acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA c) needs NADPH+H+ as a coenzyme d) includes the reaction order: dehydrogenation, hydration, dehydrogenation, cleavage it is the reaction order of -oxidation in a cytoplasm: = key regulatory enzyme „activated carbon“ Fatty acid synthesis (1 cycle) catalyzed by fatty acid synthase (cytoplasm) The figure is found at http://herkules.oulu.fi/isbn9514270312/html/graphic22.png (Jan 2007) Transport of acetyl-CoA from a mitochondrion to the cytoplasm FA synthesis NADPH from pentose cycle The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#synthesis (Jan 2007) Acetyl-CoA carboxylase a) is found in a cytoplasm b) catalyzes conversion of acetyl-CoA to oxaloacetate c) is activated by citrate d) is activated by insulin Acetyl-CoA carboxylase a) is found in a cytoplasm b) catalyzes conversion of acetyl-CoA to oxaloacetate c) is activated by citrate d) is activated by insulin Regulation of fatty acid synthesis regulatory enzyme acetyl CoA carboxylase (key enzyme) fatty acid synthase activation inhibition citrate insulin low-fat, energy rich high saccharide diet (induction) acyl-CoA (C16- C18) glucagon (phosphorylation, repression) lipid rich diet, starvation (repression) phosphorylated saccharides low-fat, energy rich high saccharide diet (induction) glucagon (phosphorylation, repression) lipid rich diet, starvation (repression) Triacylglycerol synthesis a) proceeds in a mitochondrion b) is catalyzed by lipase c) starts from glycerol-3-phosphate d) includes phosphatidic acid as an intermediate Triacylglycerol synthesis a) proceeds in a mitochondrion b) is catalyzed by lipase c) starts from glycerol-3-phosphate d) includes phosphatidic acid as an intermediate Biosynthesis of triacylglycerols The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007) Regulation of TAG metabolism regulatory enzyme activation phosphatidic acid phosphatase steroid hormones (induction) lipoprotein lipase (important for storage of TAG in a fatty tissue) insulin apolipoprotein C-II inhibition Cholesterol synthesis a) starts from acetyl-CoA b) includes the same intermediate as ketogenesis: HMG-CoA c) includes phosphoderivatives of isoprene as intermediates d) is inhibited by cholesterol Cholesterol synthesis a) starts from acetyl-CoA b) includes the same intermediate as ketogenesis: HMG-CoA c) includes phosphoderivatives of isoprene as intermediates d) is inhibited by cholesterol Biosynthesis of cholesterol regulatory enzyme The figure is found at http://web.indstate.edu/thcme/mwking/cholesterol.html (Jan 2007) activated isoprene: two frorms The figure is found at http://www.apsu.edu/reedr/Reed%20Web%20Pages/Chem%204320/Lecture%20Outlines/cholesterol_synthesis.htm (Jan 2007) cholesterol synthesis ketone bodies The figure is found at http://amiga1.med.miami.edu/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan 2007) Regulation of cholesterol synthesis regulatory enzyme HMG-CoA reductase activation insulin, thyroxine (induction) inhibition cholesterol glucagon (repression) oxosterols (repression) Cholesterol can be a) degraded to acetyl-CoA b) incorporated to cellular membrane c) esterified by a fatty acid d) transformed to bile acids Cholesterol can be a) degraded to acetyl-CoA !!! it is not degraded b) incorporated to cellular membrane c) esterified by a fatty acid d) transformed to bile acids Phospholipids a) have an amphipatic structure b) are found in lipoproteins c) contain saturated fatty acids only d) always contain glycerol Phospholipids a) have an amphipatic structure b) are found in lipoproteins c) contain saturated fatty acids only d) always contain glycerol Structure of phospholipid often unsaturated The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007) Structure of lipids The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-2/ch11_lipid-struct.jpg (Jan 2007) sphingosine ceramide = amide formed from sphingosine and fatty acid The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007) Degradation of phospholipids (hydrolysis) The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007) Glycolipids a) always contein a ceramide b) are found on the cell surface c) have an amphipatic structure d) are synthetized in a cytoplasm Glycolipids a) always contein a ceramide b) are found on the cell surface c) have an amphipatic structure d) are synthetized in a cytoplasm