Metabolism of lipids Vladimíra Kvasnicová

Lipids = group of biological molecules that are insoluble in aqueous solutions and soluble in organic solvents structural components of biological membranes energy reserves, predominantly in the form of triacylglycerols (TAG) excellent mechanical and thermal insulators biologically active compounds (vitamins, hormones, bile acids, visual pigment)

The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2 nd edition, Thieme 2005

Structural components of lipids alcohols  glycerol (a)  sfingosine (b)  cholesterol (c)  inositol (d) long chain carboxylic acids (= fatty acids) The figures are adopted from (April 2007) a) b) c) d)

The figure is found at (Jan 2007) Free Fatty Acids (FFA)

The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2 nd edition, Thieme 2005

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

The figure is found at 2/ch11_cholesterol.jpg (Jan 2007) 2/ch11_cholesterol.jpg

The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2 nd edition, Thieme 2005

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

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

Choose compounds counting among lipids a)glycerol b)triacylglycerols c)ketone bodies d)cholesterol

Choose compounds counting among lipids a)glycerol b)triacylglycerols 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, ISBN 0 ‑ 471 ‑ ‑ 2

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

typesourceprincipal lipidsimportant apoproteins they transport: chylo- microns intestineTAGB-48, C-II, E TAG from a diet to various tissues CHM remnants chylo- microns (CHM) cholesterol, TAG, phospholipids B-48, Eremnants of chylomicrons to the liver VLDLliverTAGC-II, B-100newly synthetized TAG to other tissues IDLVLDLcholesterol, TAG, phospholip. B-100VLDL remnants to other tissues LDLVLDLcholesterolB-100cholesterol to extrahepat. tissues HDLlivercholesterol, phospholipids, store of apoprot. A-I, E, C-IIcholesterol from tissues back to the liver Lipoproteins

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 is found at verheads-3/ch17_lipid-adipocytes.jpg (Jan 2007) verheads-3/ch17_lipid-adipocytes.jpg Releasing of free fatty acids from TAG of fatty tissue and their followed transport to target cells

namesourcelocation of its action functionproperties acid stable lipase stomach hydrolysis of TAG composed of short chain fatty acids stability in low pH pancreatic lipase pancreassmall 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 adipocytescytoplasm of adipocytes hydrolysis of reserve triacylglycerols activated by phosphory- lation acidic lipasevarious tissues lysosomeshydrolysis of TAGacidic pH- optimum Lipases

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

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

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

The figure was accepted from the book: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley ‑ Liss, Inc., New York, ISBN 0 ‑ 471 ‑ ‑ 2 Transport of fatty acids into a mitochondrion CARNITIN TRANSPORTER cytoplasm

Carnitine acyltransferase regulates  -oxidation regulatory enzymeactivationinhibition carnitin palmitoyltransferase I (carnitin acyltransferase)  malonyl-CoA (= intermediate of FA synthesis)

The figure was found at (January 2007) Omega-oxidation of fatty acids (endoplasmic reticulum; minority pathway for long chain FA)

 -oxidation of fatty acids a)proceeds only in the liver b)produces NADPH+H + c)is localized in mitochondria d)is activated by malonyl-CoA

 -oxidation of fatty acids a)proceeds only in the liver b)produces NADPH+H + c)is localized in mitochondria d)is activated by malonyl-CoA

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

The figure is found at (Jan 2007) Ketone bodies synthesis (= ketogenesis) proceeds if  -oxidation is  ounly in the liver: mitochondria HMG-CoA is formed also in a cytoplasm during cholesterol synthesis ! Acetyl-CoA OH

regulatory enzymeactivationinhibition hormon sensitive lipase (lipolysis in fatty tissue)   ratio glucagon / insulin  catecholamines  ratio insulin / glucagon carnitin acyltransferase I (transfer of fatty acids into mitochondria)  malonyl-Co A   ratio insulin / glucagon Regulation of ketogenesis

The figure is found at (Jan 2007) Ketone bodies degradation (oxidation) proceeds during starvation in extrahepatic tissues as an alternative energy source (in a brain as well) Citrate cycle

Ketone bodies a)are synthesized from acetyl-CoA b)are produced by muscle tissue as a consequence of increased fatty acid oxidation c)serve as an energy substrate for erythrocytes d)can be excreted with urine

Ketone bodies a)are synthesized from acetyl-CoA b)are produced by muscle tissue as a consequence of increased fatty acid oxidation c)serve as an energy substrate for erythrocytes d)can be excreted with urine

The figure is found at (Jan 2007) Fatty acid synthesis (1 cycle)

„activated carbon“

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

regulatory enzymeactivationinhibition acetyl CoA carboxylase (key enzyme)  citrate  insulin  low-fat, energy rich high saccharide diet (induction)  acyl-CoA ( C 16 - C 18 )  glucagon (phosphorylation, repression)  lipid rich diet, starvation (repression) fatty acid synthase  phosphorylated saccharides  low-fat, energy rich high saccharide diet (induction)  glucagon (phosphorylation, repression)  lipid rich diet, starvation (repression) Regulation of fatty acid synthesis

The pathway of synthesis of fatty acids a)produces NADPH+H + b)starts by carboxylation of acetyl-CoA: malonyl-CoA is formed c)is localized in mitochondria d)includes reduction steps

The pathway of synthesis of fatty acids a)produces NADPH+H + b)starts by carboxylation of acetyl-CoA: malonyl-CoA is formed c)is localized in mitochondria d)includes reduction steps

synthesis  -oxidation active under the conditionssaccharide rich dietstarvation ratio insulin/glucagonhighlow the most active tissuelivermuscles, liver cellular locationcytoplasmmitochondria transport through a mitochondrial membrane citrate (= acetyl to cytoplasm) acyl-carnitin (= acyl to matrix) acyl is bound toACP-domain, CoACoA coenzymes of oxidoreductases NADPHNAD +, FAD + C 2 donor/productmalonyl-CoA = donor of acetyl acetyl-CoA = product activator / inhibitor citrate / acyl-CoA - / malonyl-CoA productpalmitic acidacetyl-CoA Comparision of fatty acid synthesis and degradation

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

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

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

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

The figure is found at (Jan 2007) activated isoprene Synthesis of cholesterol consumes ATP

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

The figure is found at (Jan 2007)

regulatory enzymeactivationinhibition HMG-CoA reductase  insulin, thyroxine (induction)  cholesterol  glucagon (repression)  oxosterols (repression) Regulation of cholesterol synthesis

Cholesterol a)is synthesized in mitochondria b)synthesis includes the same intermediate as ketogenesis: acetone c)can be broken down to acetyl-CoA d)is synthesized if the ratio insulin/glucagon is low

Cholesterol a)is synthesized in mitochondria b)synthesis includes the same intermediate as ketogenesis: acetone c)can be broken down to acetyl-CoA d)is synthesized if the ratio insulin/glucagon is low