metabolism of lipidsvyuka-data.lf3.cuni.cz/cvse1m0001/vk_mtb_lipids_seminar(52a1e768c6a14).pdf ·...
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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, 2nd 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 http://en.wikipedia.org (April 2007)
a) b)
c) d)
The figure is found at http://www.tvdsb.on.ca/saunders/courses/online/SBI3C/Cells/Lipids.htm (Jan 2007)
Free Fatty Acids(FFA)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-2/ch11_lipid-struct.jpg(Jan 2007)
Strcture of lipids
The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-2/ch11_cholesterol.jpg (Jan 2007)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)
Structure of
phospholipid
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (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, 1997. ISBN 0-471-15451-2
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.
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.
cholesterol from tissues back to the liver
A-I, E, C-IIcholesterol, phospholipids,store of apoprot.
liverHDL
cholesterol to extrahepat. tissues
B-100cholesterolVLDLLDL
VLDL remnants to other tissues
B-100cholesterol, TAG, phospholip.
VLDLIDL
newly synthetized TAG to other tissues
C-II, B-100TAGliverVLDL
remnants of chylomicronsto the liver
B-48, Echolesterol, TAG, phospholipids
chylo-microns (CHM)
CHMremnants
TAG from a diet to various tissues
B-48, C-II, E
TAGintestinechylo-microns
they transport:important apoproteins
principal lipidssourcetype
Lipoproteins
Choose correct statements about a transport of lipids in blood
a) triacylglycerols are transfered mainly bychylomicrons 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 http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch17_lipid-adipocytes.jpg (Jan 2007)
Releasing of freefatty acids from TAG
of fatty tissue
and their followed transport
to target cells
acidic pH-optimum
hydrolysis of TAGlysosomesvarious tissues
acidic lipase
activated by phosphory-lation
hydrolysis of reservetriacylglycerols
cytoplasm of adipocytes
adipocyteshormonsensitive lipase
activated byapoC-II
hydrolysis of TAGfound in VLDL and chylomicrons
inner surface of blood vessels
extra-hepatic tissues
lipoproteinlipase
needs pancreatic colipase
hydrolysis of TAGto 2 fatty acids and 2-monoacylglycerol
small intestine
pancreaspancreaticlipase
stability in low pH
hydrolysis of TAGcomposed of short chain fatty acids
stomachstomachacid stable lipase
propertiesfunctionlocation of its action
sourcename
Lipases
Degradation of
phospholipids
(hydrolysis)
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
• insulin• apolipoprotein C-II
(apoC-II)
lipoprotein lipase(inner surface of blood vessels)
• insulin• prostaglandins
• catecholamines, glucagon(phosphorylation)
hormone sensitivelipase(in adipocytes)
inhibitionactivationregulatory enzyme
Regulation of lipolysis
The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)
ββββ-oxidation of fatty acids (1 cycle)
The figure was accepted 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
Transport of fatty acids into a mitochondrion
CARNITINE TRANSPORTER
cytoplasm
Carnitine acyltransferaseregulates ββββ-oxidation
• malonyl-CoA(= intermediate of FA synthesis)
carnitinpalmitoyltransferase I(carnitin acyltransferase)
inhibitionactivationregulatory enzyme
The figure was found at http://www.biocarta.com/pathfiles/omegaoxidationPathway.asp (January 2007)
Omega-oxidation of fatty acids
(endoplasmic reticulum; minority pathway for long
chain FA)
ββββ-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
ββββ-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 http://en.wikipedia.org/wiki/Image:Ketogenesis.png
(Jan 2007)
Ketone bodies synthesis(= ketogenesis)
• proceeds if ββββ-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)
Ketone bodies synthesis(= ketogenesis)
• proceeds if ββββ-oxidation is ↑↑↑↑
• ounly in the liver: mitochondria
HMG-CoA is formed also in a cytoplasm during cholesterol synthesis !
Acetyl-CoA
OH
• malonyl-Co A • ↑ ratio
insulin / glucagon
carnitinacyltransferase I(transfer of fatty
acids into mitochondria)
•↑ ratioinsulin / glucagon
• ↑ ratioglucagon / insulin
• catecholamines
hormon sensitivelipase(lipolysis in fatty
tissue)
inhibitionactivationregulatory enzyme
Regulation of ketogenesis
The figure is found at http://www.richmond.edu/~jbell2/19F18.JPG (Jan 2007)
Ketone bodies degradation(oxidation)
proceeds during starvationin extrahepatic tissuesas an alternative energy
source
(in a brain as well)
Citratecycle
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 http://herkules.oulu.fi/isbn9514270312/html/graphic22.png (Jan 2007)
Fatty acid synthesis
(1 cycle)
„activated carbon“
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#synthesis (Jan 2007)
Transport of acetyl-CoA from a mitochondrion to the cytoplasm
FA synthesis
NADPHfrom pentose
cycle
• glucagon (phosphorylation,
repression)• lipid rich diet,
starvation(repression)
• phosphorylated saccharides
• low-fat, energy rich high saccharide diet
(induction)
fatty acid synthase
• acyl-CoA (C16- C18)• glucagon (phosphorylation,
repression)• lipid rich diet,
starvation(repression)
• citrate• insulin• low-fat, energy
rich high saccharide diet
(induction)
acetyl CoA carboxylase
(key enzyme)
inhibitionactivationregulatory enzyme
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
acetyl-CoApalmitic acidproduct
- /malonyl-CoA
citrate /acyl-CoA
activator /inhibitor
acetyl-CoA= product
malonyl-CoA = donor of acetyl
C2 donor/product
NAD+, FAD+NADPHcoenzymes of oxidoreductases
CoAACP-domain, CoAacyl is bound to
acyl-carnitin(= acyl to matrix)
citrate(= acetyl to cytoplasm)
transport through a mitochondrial membrane
mitochondriacytoplasmcellular location
muscles, liverliverthe most active tissue
lowhighratio insulin/glucagon
starvationsaccharide rich dietactive under the conditions
ββββ-oxidationsynthesis
Comparision of fatty acid synthesis and degradation
Biosynthesis of triacylglycerols
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
• insulin• apolipoprotein C-II
lipoprotein lipase(important for storage ofTAG in a fatty tissue)
• steroid hormones(induction)
phosphatidic acid phosphatase
inhibitionactivationregulatory enzyme
Regulation of TAG metabolism
Biosynthesis of cholesterol
The figure is found at http://web.indstate.edu/thcme/mwking/cholesterol.html (Jan 2007)
regulatory enzyme
The figure is found at http://amiga1.med.miami.edu/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan 2007)
cholesterol synthesis
ketone bodies
The figure is found at http://www.apsu.edu/reedr/Reed%20Web%20Pages/Chem%204320/Lecture%20Outlines/cholesterol_synthesis.htm (Jan 2007)
activated isoprene
Synthesis of cholesterol consumes ATP
The figure is found at http://www.apsu.edu/reedr/Reed%20Web%20Pages/Chem%204320/Lecture%20Outlines/cholesterol_synthesis.htm (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• glucagon
(repression)• oxosterols
(repression)
• insulin, thyroxine(induction)
HMG-CoA reductase
inhibitionactivationregulatory enzyme
Regulation of cholesterol synthesis
Cholesterol
a) is synthesized in mitochondria
b) synthesis includes the same intermediateas 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 intermediateas ketogenesis: acetone
c) can be broken down to acetyl-CoA
d) is synthesized if the ratio insulin/glucagon is low