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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)
Structure 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) cholesterolAceton
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.
type source principal lipids
important apoprotei
ns
they transport:
chylo-microns
intestine TAG B-48, C-II, E
TAG from a diet to various tissues
CHMremnants
chylo-microns (CHM)
cholesterol, TAG, phospholipids
B-48, E remnants of chylomicronsto 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, phospholipids,store of apoprot.
A-I, E, C-II cholesterol 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 http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch17_lipid-adipocytes.jpg (Jan 2007)
Releasing of freefatty acids from
TAGof fatty tissue
and their followed transport
to target cells
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
extra-hepatic tissues
inner surface of blood vessels
hydrolysis of TAG found in VLDL and chylomicrons
activated by apoC-II
hormonsensitive lipase
adipocytes
cytoplasm of adipocytes
hydrolysis of reservetriacylglycerols
activated by phosphory-lation
acidic lipase
various tissues
lysosomes hydrolysis of TAG acidic pH-optimum
Lipases
Degradation of
phospholipids
(hydrolysis)
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
regulatory enzyme activation inhibition
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 http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (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, 1997. ISBN 0‑471‑15451‑2
Transport of fatty acids
into a mitochondrio
n
CARNITIN TRANSPORTE
R
cytoplasm
Carnitine acyltransferaseregulates -oxidation
regulatory enzyme activation
inhibition
carnitinpalmitoyltransferase
I(carnitin
acyltransferase)
malonyl-CoA(= intermediate of FA synthesis)
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)
-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 http://en.wikipedia.org/wiki/Image:Ketogenesis.png
(Jan 2007)
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)
Ketone bodies synthesis
(= ketogenesis)
• proceeds if -oxidation is
• ounly in the liver: mitochondriaHMG-CoA is formed
also in a cytoplasm during cholesterol
synthesis !
Acetyl-CoA
OH
regulatory enzyme
activation inhibition
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 http://www.richmond.edu/~jbell2/19F18.JPG (Jan 2007)
Ketone bodies degradation(oxidation)
proceeds during starvation in
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
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 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 conditions
saccharide rich diet starvation
ratio insulin/glucagon high low
the most active tissue liver muscles, liver
cellular location cytoplasm mitochondria
transport through a mitochondrial membrane
citrate(= acetyl to cytoplasm)
acyl-carnitin(= acyl to matrix)
acyl is bound to ACP-domain, CoA CoA
coenzymes of oxidoreductases
NADPH NAD+, FAD+
C2 donor/product malonyl-CoA = donor of acetyl
acetyl-CoA= product
activator /inhibitor
citrate /acyl-CoA
- /malonyl-CoA
product palmitic acid acetyl-CoA
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)
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
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 isopreneSynthesis 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)
regulatory enzyme
activation inhibition
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 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
