Lipids
= group of biological molecules that are
insoluble in aqueous solutions
and soluble in organic solvents
Metabolism of lipids
Vladimíra Kvasnicová
• 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)
Structural components of lipids
• alcohols
glycerol (a)
sfingosine (b)
cholesterol (c)
inositol (d)
a)
b)
c)
d)
• long chain carboxylic acids
(= fatty acids)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
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
Strcture 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)
Structure
of
phospholipid
The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)
The figure was adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005
Choose compounds counting among lipids
sphingosine
a) glycerol
b) triacylglycerols
c) ketone bodies
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)
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.
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
The figure was accepted from the book: Grundy, S.M.: Atlas of lipid disorders, unit 1. Gower Medical Publishing, New York, 1990.
Choose correct statements about a
transport of lipids in blood
Choose correct statements about a
transport of lipids in blood
a) triacylglycerols are transfered mainly by
chylomicrons and VLDL
a) triacylglycerols are transfered mainly by
chylomicrons and VLDL
b) free fatty acids are bound to albumin
b) free fatty acids are bound to albumin
c) cholesterol is transfered mainly by HDL
and LDL
c) cholesterol is transfered mainly by HDL
and LDL
d) ketone bodies do not need a transport
protein
d) ketone bodies do not need a transport
protein
Lipases
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)
Degradation
of
phospholipids
(hydrolysis)
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
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
Regulation of lipolysis
regulatory enzyme
hormone sensitive
lipase
(in adipocytes)
lipoprotein lipase
(inner surface of
blood vessels)
activation
inhibition
• catecholamines,
• insulin
glucagon
• prostaglandins
(phosphorylation)
• insulin
• apolipoprotein C-II
(apoC-II)
β-oxidation of fatty acids
cytoplasm
(1 cycle)
Transport of
fatty acids into
a mitochondrion
CARNITINE
TRANSPORTER
The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)
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 β-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)
β-oxidation of fatty acids
β-oxidation of fatty acids
a) proceeds only in the liver
a) proceeds only in the liver
b) produces NADPH+H+
b) produces NADPH+H+
c) is localized in mitochondria
c) is localized in mitochondria
d) is activated by malonyl-CoA
d) is activated by malonyl-CoA
Ketone bodies synthesis
(= ketogenesis)
Ketone bodies synthesis
(= ketogenesis)
• proceeds if β-oxidation is ↑
• proceeds if β-oxidation is ↑
• ounly in the liver: mitochondria
• ounly in the liver: mitochondria
Acetyl-CoA
HMG-CoA is formed also
in a cytoplasm during
cholesterol synthesis !
OH
The figure is found at
http://en.wikipedia.org/wiki/Image:Ketogenesis.png
(Jan 2007)
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
Ketone bodies
a) are synthesized from acetyl-CoA
a) are synthesized from acetyl-CoA
b) are produced by muscle tissue as a
consequence of increased fatty acid
oxidation
b) are produced by muscle tissue as a
consequence of increased fatty acid
oxidation
c) serve as an energy substrate for
erythrocytes
c) serve as an energy substrate for
erythrocytes
d) can be excreted with urine
d) can be excreted with urine
Fatty acid synthesis
(1 cycle)
„activated carbon“
The figure is found at
http://herkules.oulu.fi/isbn9514270312/html/graphic22.png (Jan 2007)
Transport of acetyl-CoA from a mitochondrion
to the cytoplasm
Regulation of fatty acid synthesis
regulatory enzyme
acetyl CoA
carboxylase
(key enzyme)
FA synthesis
fatty acid
synthase
NADPH
from pentose
cycle
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#synthesis (Jan 2007)
activation
• citrate
• insulin
• low-fat, energy
rich high
saccharide diet
(induction)
• phosphorylated
saccharides
• low-fat, energy
rich high
saccharide diet
(induction)
inhibition
• acyl-CoA (C16- C18)
• glucagon
(phosphorylation,
repression)
• lipid rich diet,
starvation
(repression)
• glucagon
(phosphorylation,
repression)
• lipid rich diet,
starvation
(repression)
The pathway of synthesis of fatty acids
The pathway of synthesis of fatty acids
a) produces NADPH+H+
a) produces NADPH+H+
b) starts by carboxylation of acetyl-CoA:
malonyl-CoA is formed
b) starts by carboxylation of acetyl-CoA:
malonyl-CoA is formed
c) is localized in mitochondria
c) is localized in mitochondria
d) includes reduction steps
d) includes reduction steps
Comparision of fatty acid synthesis and degradation
Biosynthesis of triacylglycerols
β-oxidation
synthesis
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
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
Biosynthesis of cholesterol
regulatory enzyme
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
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)
Cholesterol
Regulation of cholesterol synthesis
regulatory enzyme
HMG-CoA
reductase
activation
• insulin, thyroxine
(induction)
inhibition
• cholesterol
• glucagon
(repression)
• oxosterols
(repression)
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