Transcript ppt

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)
a)
b)
c)
d)
• long chain carboxylic acids
(= fatty acids)
The figures are adopted from http://en.wikipedia.org (April 2007)
Free Fatty Acids
(FFA)
The figure is found at http://www.tvdsb.on.ca/saunders/courses/online/SBI3C/Cells/Lipids.htm (Jan 2007)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
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)
The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads2/ch11_cholesterol.jpg (Jan 2007)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
Structure
of
phospholipid
The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.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)
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.
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
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
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)
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
Degradation
of
phospholipids
(hydrolysis)
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
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
-oxidation of fatty acids
(1 cycle)
dehydrogenation
The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)
cytoplasm
Transport of
fatty acids into
a mitochondrion
CARNITIN
TRANSPORTER
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
Carnitine acyltransferase
regulates -oxidation
regulatory enzyme
carnitin
palmitoyltransferase I
(carnitin acyltransferase)
activation
inhibition
 malonyl-CoA
(= intermediate
of FA synthesis)
Omega-oxidation
of fatty acids
(endoplasmic
reticulum; minority
pathway for long
chain FA)
The figure was found at http://www.biocarta.com/pathfiles/omegaoxidationPathway.asp (January 2007)
-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
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: mitochondria
HMG-CoA is formed also
in a cytoplasm during
cholesterol synthesis !
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)
carnitin
 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)
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
Fatty acid synthesis
(1 cycle)
The figure is found at
http://herkules.oulu.fi/isbn9514270312/html/graphic22.png (Jan 2007)
„activated carbon“
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)
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)
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
Comparision of fatty acid synthesis and degradation
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
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
Biosynthesis of cholesterol
regulatory enzyme
The figure is found at http://web.indstate.edu/thcme/mwking/cholesterol.html (Jan 2007)
cholesterol synthesis
ketone bodies
The figure is found at http://amiga1.med.miami.edu/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan 2007)
Synthesis of cholesterol
consumes ATP
activated isoprene
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)
The figure is found at
http://www.apsu.edu/reedr/Reed%20Web%20Pages/Chem%204320/Lecture%20Outlines/cholesterol_synthesis.htm (Jan 2007)
Regulation of cholesterol synthesis
regulatory enzyme
HMG-CoA
reductase
activation
 insulin, thyroxine
(induction)
inhibition
 cholesterol
 glucagon
(repression)
 oxosterols
(repression)
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