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Metabolism of lipids - exercise -

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1 Metabolism of lipids - exercise -
Vladimíra Kvasnicová

2 Choose compounds counting among lipids
fatty acids and glycerol triacylglycerols and phospholipids ketone bodies cholesterol

3 Choose compounds counting among lipids
fatty acids and glycerol TAG and phospholipids ketone bodies 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, ISBN 0‑471‑15451‑2

4 Free Fatty Acids = FFA a hydrophobic hydrocarbon sceleton predominates
The figure is found at (Jan 2007)

5 a hydrophobic hydrocarbon sceleton predominates
The figure is found at (Jan 2007)

6 Lipoproteins contain a phospholipid bilayer on their surface
free cholesterol in their core triacylglycerols in their core surface proteins having a role of ligands, which can bind to receptors of target cells

7 Lipoproteins contain a phospholipid bilayer on their surface
free cholesterol in their core triacylglycerols in their core 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

8 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.

9 Choose correct statements about a transport of lipids in blood
triacylglycerols are transfered mainly by chylomicrons and VLDL free fatty acids are bound to albumin cholesterol is transfered mainly by HDL and LDL ketone bodies do not need a transport protein

10 Choose correct statements about a transport of lipids in blood
triacylglycerols are transfered mainly by chylomicrons and VLDL free fatty acids are bound to albumin cholesterol is transfered mainly by HDL and LDL ketone bodies do not need a transport protein

11 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

12 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

13 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

14 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

15 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

16 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

17 The figure was accepted from the book: Grundy, S. M
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.

18 Releasing of free fatty acids from TAG of fatty tissue
and their followed transport to target cells The figure is found at (Jan 2007)

19 Choose correct statements about properties of lipoproteins
chylomicrons are formed in enterocytes VLDL conteins the apoC-II - an activator of a lipoprotein lipase apoproteins A (apoA) are specific for LDL HDL transfers cholesterol from the liver to extrahepatic tissues

20 Choose correct statements about properties of lipoproteins
chylomicrons are formed in enterocytes VLDL conteins the apoC-II - an activator of a lipoprotein lipase apoproteins A (apoA) are specific for LDL HDL transfers cholesterol from the liver to extrahepatic tissues

21 important apoproteins
Lipoproteins type source principal lipids important apoproteins they transport: chylo- microns intestine TAG B-48, C-II, E TAG from a diet to various tissues CHM remnants chylo- microns (CHM) cholesterol, TAG, phospholipids B-48, E remnants of chylomicrons to the liver VLDL liver C-II, B-100 newly synthetized TAG to other tissues IDL cholesterol, TAG, phospholip. B-100 VLDL remnants to other tissues LDL cholesterol cholesterol to extrahepat. tissues HDL cholesterol, phospholipids, store of apoprot. A-I, E, C-II cholesterol from tissues back to the liver

22 Lipases catalyze cleavage of fatty acids
catalyze cleavage of cholesterol esters are found on the inner surface of blood vessels are found in the adipose tissue

23 Lipases catalyze cleavage of fatty acids
catalyze cleavage of cholesterol esters are found on the inner surface of blood vessels = lipoprotein lipase are found in the adipose tissue = hormone sensitive lipase

24 Lipases name source location of its action function properties
acid stable lipase 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 extra- hepatic 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 phosphory-lation acidic lipase various tissues lysosomes acidic pH-optimum

25 Regulation of lipolysis
regulatory enzyme activation inhibition hormone sensitive lipase (in adipocytes) catecholamines, glucagon (phosphorylation) insulin prostaglandins lipoprotein lipase (inner surface of blood vessels) apolipoprotein C-II (apoC-II)

26 Fatty acids can contain double bonds
are found in the fatty tissue in their esterified form are found in membrane phospholipids can be converted to ketone bodies

27 Fatty acids can contain double bonds
are found in the fatty tissue in their esterified form as triacylglycerols (TAG) are found in membrane phospholipids can be converted to ketone bodies

28 -oxidation of fatty acids
proceeds in a mitochondrion produces oxidized forms of coenzymes proceeds in a nervous tissue as well is regulated on the level of FFA transport into the mitochondrion

29 -oxidation of fatty acids
proceeds in a mitochondrion produces oxidized forms of coenzymes proceeds in a nervous tissue as well is regulated on the level of FFA transport into the mitochondrion carnitine transporter

30 -oxidation of fatty acids (1 cycle)
The figure is found at (Jan 2007)

31 Carnitine acyltransferase
is activated by malonyl-CoA transfers the molecule of acyl-CoA into the mitochondrion transfers acyls of the maximal length of 18 carbons transfers carnitin out of the mitoch. matrix

32 Carnitine acyltransferase
is activated by malonyl-CoA transfers the molecule of acyl-CoA into the mitochondrion transfers acyls of the maximal length of 18 carbons transfers carnitin out of the mitoch. matrix regulatory enzyme activation inhibition carnitin palmitoyltransferase I (carnitin acyltransferase) malonyl-CoA (= intermediate of FA synthesis)

33 Transport of fatty acids into a mitochondrion CARNITINE TRANSPORTER
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, ISBN 0‑471‑15451‑2

34 Acetyl-CoA generated by -oxidation can be
oxidized in a citrate cycle transformed to ketone bodies transformed to glucose used in a cholesterol synthesis

35 Acetyl-CoA generated by -oxidation can be
oxidized in a citrate cycle transformed to ketone bodies transformed to glucose !!! used in a cholesterol synthesis Acetyl-CoA can not be converted to pyruvate: pyruvate dehydrogenase reaction is irreversible.

36 Ketone bodies can be used as an energy substrate for the liver
are formed in various tissues can be transformed to glucose can be oxidized to CO2 and water

37 Ketone bodies can be used as an energy substrate for the liver
are formed in various tissues can be transformed to glucose !!! can be oxidized to CO2 and water

38 Ketone bodies synthesis (= ketogenesis)
proceeds if -oxidation is  ounly in the liver: mitochondria Acetyl-CoA OH The figure is found at (Jan 2007)

39 Regulation of ketogenesis
regulatory enzyme activation inhibition hormon sensitive lipase (lipolysis in fatty tissue)  ratio glucagon / insulin catecholamines  ratio insulin / glucagon carnitine acyltransferase I (transfer of fatty acids into mitochondria) malonyl-Co A  ratio insulin / glucagon

40 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 (Jan 2007)

41 Fatty acid synthesis proceeds in a mitochondrion
starts by the reaction: acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA needs NADPH+H+ as a coenzyme includes the reaction order: dehydrogenation, hydration, dehydrogenation, cleavage

42 Fatty acid synthesis proceeds in a mitochondrion
starts by the reaction: acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA needs NADPH+H+ as a coenzyme includes the reaction order: dehydrogenation, hydration, dehydrogenation, cleavage it is the reaction order of -oxidation

43 in a cytoplasm: = key regulatory enzyme „activated carbon“

44 catalyzed by fatty acid synthase (cytoplasm)
Fatty acid synthesis (1 cycle) catalyzed by fatty acid synthase (cytoplasm) The figure is found at (Jan 2007)

45 Transport of acetyl-CoA from a mitochondrion to the cytoplasm
FA synthesis NADPH from pentose cycle The figure is found at (Jan 2007)

46 Acetyl-CoA carboxylase
is found in a cytoplasm catalyzes conversion of acetyl-CoA to oxaloacetate is activated by citrate is activated by insulin

47 Acetyl-CoA carboxylase
is found in a cytoplasm catalyzes conversion of acetyl-CoA to oxaloacetate is activated by citrate is activated by insulin

48 Regulation of fatty acid synthesis
regulatory enzyme activation inhibition acetyl CoA carboxylase (key enzyme) citrate insulin low-fat, energy rich high saccharide diet (induction) acyl-CoA (C16- C18) glucagon (phosphorylation, repression) lipid rich diet, starvation (repression) fatty acid synthase phosphorylated saccharides glucagon (phosphorylation, repression)

49 Triacylglycerol synthesis
proceeds in a mitochondrion is catalyzed by lipase starts from glycerol-3-phosphate includes phosphatidic acid as an intermediate

50 Triacylglycerol synthesis
proceeds in a mitochondrion is catalyzed by lipase starts from glycerol-3-phosphate includes phosphatidic acid as an intermediate

51 Biosynthesis of triacylglycerols
The figure is found at (Jan 2007)

52 Regulation of TAG metabolism
regulatory enzyme activation inhibition phosphatidic acid phosphatase steroid hormones (induction) lipoprotein lipase (important for storage of TAG in a fatty tissue) insulin apolipoprotein C-II

53 Cholesterol synthesis
starts from acetyl-CoA includes the same intermediate as ketogenesis: HMG-CoA includes phosphoderivatives of isoprene as intermediates is inhibited by cholesterol

54 Cholesterol synthesis
starts from acetyl-CoA includes the same intermediate as ketogenesis: HMG-CoA includes phosphoderivatives of isoprene as intermediates is inhibited by cholesterol

55 Biosynthesis of cholesterol
regulatory enzyme The figure is found at (Jan 2007)

56 activated isoprene: two frorms
The figure is found at (Jan 2007)

57 cholesterol synthesis
ketone bodies The figure is found at (Jan 2007)

58 Regulation of cholesterol synthesis
regulatory enzyme activation inhibition HMG-CoA reductase insulin, thyroxine (induction) cholesterol glucagon (repression) oxosterols (repression)

59 Cholesterol can be degraded to acetyl-CoA
incorporated to cellular membrane esterified by a fatty acid transformed to bile acids

60 Cholesterol can be degraded to acetyl-CoA !!! it is not degraded
incorporated to cellular membrane esterified by a fatty acid transformed to bile acids

61 Phospholipids have an amphipatic structure are found in lipoproteins
contain saturated fatty acids only always contain glycerol

62 Phospholipids have an amphipatic structure are found in lipoproteins
contain saturated fatty acids only always contain glycerol

63 Structure of phospholipid
often unsaturated The figure is found at (Jan 2007)

64 Structure of lipids The figure is found at (Jan 2007)

65 sphingosine ceramide = amide formed from sphingosine and fatty acid
The figure is found at (Jan 2007)

66 Degradation of phospholipids
(hydrolysis) The figure is found at (Jan 2007)

67 Glycolipids always contein a ceramide are found on the cell surface
have an amphipatic structure are synthetized in a cytoplasm

68 Glycolipids always contein a ceramide are found on the cell surface
have an amphipatic structure are synthetized in a cytoplasm


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