Transcript Metabolism of lipids

Metabolism of lipids
- exercise -
Vladimíra Kvasnicová
Choose compounds counting among lipids
a) fatty acids and glycerol
b) triacylglycerols and phospholipids
c) ketone bodies
d) cholesterol
Choose compounds counting among lipids
a) fatty acids and glycerol
b) TAG and phospholipids
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
Free Fatty Acids = FFA
a hydrophobic hydrocarbon sceleton predominates
The figure is found at http://www.tvdsb.on.ca/saunders/courses/online/SBI3C/Cells/Lipids.htm (Jan 2007)
a hydrophobic hydrocarbon sceleton predominates
The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads2/ch11_cholesterol.jpg (Jan 2007)
Lipoproteins contain
a) a phospholipid bilayer on their surface
b) free cholesterol in their core
c) triacylglycerols in their core
d) surface proteins having a role of ligands,
which can bind to receptors of target cells
Lipoproteins contain
a) a phospholipid bilayer on their surface
b) free cholesterol in their core
c) triacylglycerols in their core
d) surface proteins having a role of ligands,
which can bind to receptors of target cells
other functions: apoproteins activate enzymes metabolizing
lipoproteins, or they have a structural function
lipids are transported in a form of lipoproteins in blood
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
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 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.
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)
Choose correct statements about
properties of lipoproteins
a) chylomicrons are formed in enterocytes
b) VLDL conteins the apoC-II - an activator
of a lipoprotein lipase
c) apoproteins A (apoA) are specific for LDL
d) HDL transfers cholesterol from the liver
to extrahepatic tissues
Choose correct statements about
properties of lipoproteins
a) chylomicrons are formed in enterocytes
b) VLDL conteins the apoC-II - an activator
of a lipoprotein lipase
c) apoproteins A (apoA) are specific for LDL
d) HDL transfers cholesterol from the liver
to extrahepatic tissues
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
Lipases
a) catalyze cleavage of fatty acids
b) catalyze cleavage of cholesterol esters
c) are found on the inner surface of blood
vessels
d) are found in the adipose tissue
Lipases
a) catalyze cleavage of fatty acids
b) catalyze cleavage of cholesterol esters
c) are found on the inner surface of blood
vessels
= lipoprotein lipase
d) are found in the adipose tissue
= hormone sensitive lipase
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
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
Fatty acids
a) can contain double bonds
b) are found in the fatty tissue in their
esterified form
c) are found in membrane phospholipids
d) can be converted to ketone bodies
Fatty acids
a) can contain double bonds
b) are found in the fatty tissue in their
esterified form as triacylglycerols (TAG)
c) are found in membrane phospholipids
d) can be converted to ketone bodies
-oxidation of fatty acids
a) proceeds in a mitochondrion
b) produces oxidized forms of coenzymes
c) proceeds in a nervous tissue as well
d) is regulated on the level of FFA transport
into the mitochondrion
-oxidation of fatty acids
a) proceeds in a mitochondrion
b) produces oxidized forms of coenzymes
c) proceeds in a nervous tissue as well
d) is regulated on the level of FFA transport
into the mitochondrion carnitine transporter
-oxidation of fatty acids
(1 cycle)
The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)
Carnitine acyltransferase
a) is activated by malonyl-CoA
b) transfers the molecule of acyl-CoA into the
mitochondrion
c) transfers acyls of the maximal length of 18
carbons
d) transfers carnitin out of the mitoch. matrix
Carnitine acyltransferase
a) is activated by malonyl-CoA
b) transfers the molecule of acyl-CoA into the
mitochondrion
c) transfers acyls of the maximal length of 18
carbons
d) transfers carnitin out of the mitoch. matrix
regulatory enzyme
carnitin
palmitoyltransferase I
(carnitin acyltransferase)
activation
inhibition
 malonyl-CoA
(= intermediate
of FA synthesis)
cytoplasm
Transport of
fatty acids into
a mitochondrion
CARNITINE
TRANSPORTER
The figure was adopted 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
Acetyl-CoA generated by -oxidation
can be
a) oxidized in a citrate cycle
b) transformed to ketone bodies
c) transformed to glucose
d) used in a cholesterol synthesis
Acetyl-CoA generated by -oxidation
can be
a) oxidized in a citrate cycle
b) transformed to ketone bodies
c) transformed to glucose !!!
d) used in a cholesterol synthesis
Acetyl-CoA can not be converted to pyruvate:
pyruvate dehydrogenase reaction is irreversible.
Ketone bodies
a) can be used as an energy substrate for the
liver
b) are formed in various tissues
c) can be transformed to glucose
d) can be oxidized to CO2 and water
Ketone bodies
a) can be used as an energy substrate for the
liver
b) are formed in various tissues
c) can be transformed to glucose !!!
d) can be oxidized to CO2 and water
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)
Regulation of ketogenesis
regulatory enzyme
activation
inhibition
hormon sensitive   ratio
 ratio
lipase
glucagon / insulin
insulin / glucagon
(lipolysis in fatty  catecholamines
tissue)
carnitine
 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)
Fatty acid synthesis
a) proceeds in a mitochondrion
b) starts by the reaction:
acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA
c) needs NADPH+H+ as a coenzyme
d) includes the reaction order: dehydrogenation,
hydration, dehydrogenation, cleavage
Fatty acid synthesis
a) proceeds in a mitochondrion
b) starts by the reaction:
acetyl-CoA + acetyl-CoA → acatoacetyl-CoA + CoA
c) needs NADPH+H+ as a coenzyme
d) includes the reaction order: dehydrogenation,
hydration, dehydrogenation, cleavage
it is the reaction order of -oxidation
in a cytoplasm:
= key regulatory
enzyme
„activated carbon“
Fatty acid synthesis
(1 cycle)
catalyzed by
fatty acid synthase
(cytoplasm)
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
FA synthesis
NADPH
from pentose
cycle
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#synthesis (Jan 2007)
Acetyl-CoA carboxylase
a) is found in a cytoplasm
b) catalyzes conversion of acetyl-CoA to
oxaloacetate
c) is activated by citrate
d) is activated by insulin
Acetyl-CoA carboxylase
a) is found in a cytoplasm
b) catalyzes conversion of acetyl-CoA to
oxaloacetate
c) is activated by citrate
d) is activated by insulin
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)
Triacylglycerol synthesis
a) proceeds in a mitochondrion
b) is catalyzed by lipase
c) starts from glycerol-3-phosphate
d) includes phosphatidic acid as an intermediate
Triacylglycerol synthesis
a) proceeds in a mitochondrion
b) is catalyzed by lipase
c) starts from glycerol-3-phosphate
d) includes phosphatidic acid as an intermediate
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
Cholesterol synthesis
a) starts from acetyl-CoA
b) includes the same intermediate as
ketogenesis: HMG-CoA
c) includes phosphoderivatives of isoprene as
intermediates
d) is inhibited by cholesterol
Cholesterol synthesis
a) starts from acetyl-CoA
b) includes the same intermediate as
ketogenesis: HMG-CoA
c) includes phosphoderivatives of isoprene as
intermediates
d) is inhibited by cholesterol
Biosynthesis of cholesterol
regulatory enzyme
The figure is found at http://web.indstate.edu/thcme/mwking/cholesterol.html (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 synthesis
ketone bodies
The figure is found at http://amiga1.med.miami.edu/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan 2007)
Regulation of cholesterol synthesis
regulatory enzyme
HMG-CoA
reductase
activation
 insulin, thyroxine
(induction)
inhibition
 cholesterol
 glucagon
(repression)
 oxosterols
(repression)
Cholesterol can be
a) degraded to acetyl-CoA
b) incorporated to cellular membrane
c) esterified by a fatty acid
d) transformed to bile acids
Cholesterol can be
a) degraded to acetyl-CoA !!! it is not degraded
b) incorporated to cellular membrane
c) esterified by a fatty acid
d) transformed to bile acids
Phospholipids
a) have an amphipatic structure
b) are found in lipoproteins
c) contain saturated fatty acids only
d) always contain glycerol
Phospholipids
a) have an amphipatic structure
b) are found in lipoproteins
c) contain saturated fatty acids only
d) always contain glycerol
Structure
of
phospholipid
often
unsaturated
The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)
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)
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)
Degradation
of
phospholipids
(hydrolysis)
The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)
Glycolipids
a) always contein a ceramide
b) are found on the cell surface
c) have an amphipatic structure
d) are synthetized in a cytoplasm
Glycolipids
a) always contein a ceramide
b) are found on the cell surface
c) have an amphipatic structure
d) are synthetized in a cytoplasm