Metabolism of lipids - exercise -

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Metabolism of lipids- exercise -

• Vladimíra Kvasnicová

2
Choose compounds counting among lipids

1. fatty acids and glycerol
2. triacylglycerols and phospholipids
3. ketone bodies
4. cholesterol

3
Choose compounds counting among lipids

1. fatty acids and glycerol
2. TAG and phospholipids
3. ketone bodies
4. 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
4
Free Fatty Acids FFAa hydrophobic hydrocarbon
sceleton predominates
The figure is found at http//www.tvdsb.on.ca/saun
ders/courses/online/SBI3C/Cells/Lipids.htm (Jan
2007)
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a hydrophobic hydrocarbon sceleton predominates
The figure is found at http//courses.cm.utexas.ed
u/archive/Spring2002/CH339K/Robertus/overheads-2/c
h11_cholesterol.jpg (Jan 2007)
6
Lipoproteins contain

1. a phospholipid bilayer on their surface
2. free cholesterol in their core
3. triacylglycerols in their core
4. surface proteins having a role of ligands, which
   can bind to receptors of target cells

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Lipoproteins contain

1. a phospholipid bilayer on their surface
2. free cholesterol in their core
3. triacylglycerols in their core
4. surface proteins having a role of ligands, which
   can bind to receptors of target cellsother
   functions apoproteins activate enzymes
   metabolizing lipoproteins, or they have a
   structural function

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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.
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Choose correct statements about a transport of
lipids in blood

1. triacylglycerols are transfered mainly by
   chylomicrons and VLDL
2. free fatty acids are bound to albumin
3. cholesterol is transfered mainly by HDL and LDL
4. ketone bodies do not need a transport protein

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Choose correct statements about a transport of
lipids in blood

1. triacylglycerols are transfered mainly by
   chylomicrons and VLDL
2. free fatty acids are bound to albumin
3. cholesterol is transfered mainly by HDL and LDL
4. ketone bodies do not need a transport protein

11
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
12
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
13
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
14
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
15
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
16
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
17
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
18
Releasing of freefatty acids from TAGof fatty
tissue and their followed transportto target
cells
The figure is found at http//courses.cm.utexas.ed
u/archive/Spring2002/CH339K/Robertus/overheads-3/c
h17_lipid-adipocytes.jpg (Jan 2007)
19
Choose correct statements about properties of
lipoproteins

1. chylomicrons are formed in enterocytes
2. VLDL conteins the apoC-II - an activator of a
   lipoprotein lipase
3. apoproteins A (apoA) are specific for LDL
4. HDL transfers cholesterol from the liver to
   extrahepatic tissues

20
Choose correct statements about properties of
lipoproteins

1. chylomicrons are formed in enterocytes
2. VLDL conteins the apoC-II - an activator of a
   lipoprotein lipase
3. apoproteins A (apoA) are specific for LDL
4. HDL transfers cholesterol from the liver to
   extrahepatic tissues

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Lipoproteins
type source principal lipids important apoproteins 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 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, phospholipids,store of apoprot. A-I, E, C-II cholesterol from tissues back to the liver
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Lipases

1. catalyze cleavage of fatty acids
2. catalyze cleavage of cholesterol esters
3. are found on the inner surface of blood vessels
4. are found in the adipose tissue

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Lipases

1. catalyze cleavage of fatty acids
2. catalyze cleavage of cholesterol esters
3. are found on the inner surface of blood vessels
   lipoprotein lipase
4. are found in the adipose tissue hormone
   sensitive lipase

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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 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 reserve triacylglycerols activated by phosphory-lation
acidic lipase various tissues lysosomes hydrolysis of TAG acidic pH-optimum
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Regulation of lipolysis
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)
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Fatty acids

1. can contain double bonds
2. are found in the fatty tissue in their esterified
   form
3. are found in membrane phospholipids
4. can be converted to ketone bodies

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Fatty acids

1. can contain double bonds
2. are found in the fatty tissue in their esterified
   form as triacylglycerols (TAG)
3. are found in membrane phospholipids
4. can be converted to ketone bodies

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?-oxidation of fatty acids

1. proceeds in a mitochondrion
2. produces oxidized forms of coenzymes
3. proceeds in a nervous tissue as well
4. is regulated on the level of FFA transport into
   the mitochondrion

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?-oxidation of fatty acids

1. proceeds in a mitochondrion
2. produces oxidized forms of coenzymes
3. proceeds in a nervous tissue as well
4. is regulated on the level of FFA transport into
   the mitochondrion carnitine transporter

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?-oxidation of fatty acids (1 cycle)
The figure is found at http//www.biocarta.com/pat
hfiles/betaoxidationPathway.asp (Jan 2007)
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Carnitine acyltransferase

1. is activated by malonyl-CoA
2. transfers the molecule of acyl-CoA into the
   mitochondrion
3. transfers acyls of the maximal length of 18
   carbons
4. transfers carnitin out of the mitoch. matrix

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Carnitine acyltransferase

1. is activated by malonyl-CoA
2. transfers the molecule of acyl-CoA into the
   mitochondrion
3. transfers acyls of the maximal length of 18
   carbons
4. transfers carnitin out of the mitoch. matrix

regulatory enzyme activation inhibition
carnitin palmitoyltransferase I (carnitin acyltransferase) malonyl-CoA( intermediate of FA synthesis)
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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
34
Acetyl-CoA generated by ?-oxidation can be

1. oxidized in a citrate cycle
2. transformed to ketone bodies
3. transformed to glucose
4. used in a cholesterol synthesis

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Acetyl-CoA generated by ?-oxidation can be

• oxidized in a citrate cycle
• transformed to ketone bodies
• transformed to glucose !!!
• used in a cholesterol synthesis
• Acetyl-CoA can not be converted to
  pyruvatepyruvate dehydrogenase reaction is
  irreversible.

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Ketone bodies

1. can be used as an energy substrate for the liver
2. are formed in various tissues
3. can be transformed to glucose
4. can be oxidized to CO2 and water

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Ketone bodies

1. can be used as an energy substrate for the liver
2. are formed in various tissues
3. can be transformed to glucose !!!
4. can be oxidized to CO2 and water

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• 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/wik
i/ImageKetogenesis.png (Jan 2007)
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Regulation of ketogenesis
regulatory enzyme activation inhibition
hormon sensitive lipase (lipolysis in fatty tissue) ? ratio glucagon / insulin catecholamines ? ratio insulin / glucagon
carnitine acyltransferase I (transfer of fatty acids into mitochondria) malonyl-Co A ? ratio insulin / glucagon
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Ketone bodies degradation(oxidation) proceeds
during starvation in extrahepatic tissuesas an
alternative energy source (in a brain as well)
Citratecycle
The figure is found at http//www.richmond.edu/jb
ell2/19F18.JPG (Jan 2007)
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Fatty acid synthesis

1. proceeds in a mitochondrion
2. starts by the reactionacetyl-CoA acetyl-CoA ?
   acatoacetyl-CoA CoA
3. needs NADPHH as a coenzyme
4. includes the reaction order dehydrogenation,
   hydration, dehydrogenation, cleavage

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Fatty acid synthesis

1. proceeds in a mitochondrion
2. starts by the reactionacetyl-CoA acetyl-CoA ?
   acatoacetyl-CoA CoA
3. needs NADPHH as a coenzyme
4. includes the reaction order dehydrogenation,
   hydration, dehydrogenation, cleavageit is the
   reaction order of ?-oxidation

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in a cytoplasm
key regulatory enzyme
activated carbon
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Fatty acid synthesis (1 cycle) catalyzed
byfatty acid synthase(cytoplasm)
The figure is found at http//herkules.oulu.fi/isb
n9514270312/html/graphic22.png (Jan 2007)
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Transport of acetyl-CoA from a mitochondrion to
the cytoplasm
FA synthesis
NADPHfrom pentose cycle
The figure is found at http//web.indstate.edu/thc
me/mwking/lipid-synthesis.htmlsynthesis (Jan
2007)
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Acetyl-CoA carboxylase

1. is found in a cytoplasm
2. catalyzes conversion of acetyl-CoA to
   oxaloacetate
3. is activated by citrate
4. is activated by insulin

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Acetyl-CoA carboxylase

1. is found in a cytoplasm
2. catalyzes conversion of acetyl-CoA to
   oxaloacetate
3. is activated by citrate
4. is activated by insulin

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Regulation of fatty acid synthesis
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)
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Triacylglycerol synthesis

1. proceeds in a mitochondrion
2. is catalyzed by lipase
3. starts from glycerol-3-phosphate
4. includes phosphatidic acid as an intermediate

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Triacylglycerol synthesis

1. proceeds in a mitochondrion
2. is catalyzed by lipase
3. starts from glycerol-3-phosphate
4. includes phosphatidic acid as an intermediate

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Biosynthesis of triacylglycerols

• The figure is found at http//web.indstate.edu/th
  cme/mwking/lipid-synthesis.htmlphospholipids
  (Jan 2007)

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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
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Cholesterol synthesis

1. starts from acetyl-CoA
2. includes the same intermediate as ketogenesis
   HMG-CoA
3. includes phosphoderivatives of isoprene as
   intermediates
4. is inhibited by cholesterol

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Cholesterol synthesis

1. starts from acetyl-CoA
2. includes the same intermediate as ketogenesis
   HMG-CoA
3. includes phosphoderivatives of isoprene as
   intermediates
4. is inhibited by cholesterol

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Biosynthesis of cholesterol
regulatory enzyme

• The figure is found at http//web.indstate.edu/thc
  me/mwking/cholesterol.html (Jan 2007)

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activated isoprene two frorms
The figure is found at http//www.apsu.edu/reedr/R
eed20Web20Pages/Chem204320/Lecture20Outlines/c
holesterol_synthesis.htm (Jan 2007)
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cholesterol synthesis
ketone bodies
The figure is found at http//amiga1.med.miami.edu
/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan
2007)
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Regulation of cholesterol synthesis
regulatory enzyme activation inhibition
HMG-CoA reductase insulin, thyroxine (induction) cholesterol glucagon (repression) oxosterols (repression)
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Cholesterol can be

1. degraded to acetyl-CoA
2. incorporated to cellular membrane
3. esterified by a fatty acid
4. transformed to bile acids

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Cholesterol can be

1. degraded to acetyl-CoA !!! it is not degraded
2. incorporated to cellular membrane
3. esterified by a fatty acid
4. transformed to bile acids

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Phospholipids

1. have an amphipatic structure
2. are found in lipoproteins
3. contain saturated fatty acids only
4. always contain glycerol

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Phospholipids

1. have an amphipatic structure
2. are found in lipoproteins
3. contain saturated fatty acids only
4. always contain glycerol

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Structure of phospholipid
oftenunsaturated
The figure is found at http//www.mie.utoronto.ca/
labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)
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Structure of lipids
The figure is found at http//courses.cm.utexas.ed
u/archive/Spring2002/CH339K/Robertus/overheads-2/c
h11_lipid-struct.jpg(Jan 2007)
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sphingosine ceramide amide formed from
sphingosine and fatty acid
The figure is found at http//web.indstate.edu/thc
me/mwking/lipid-synthesis.htmlphospholipids (Jan
2007)
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Degradation of phospholipids (hydrolysis)
The figure is found at http//web.indstate.edu/thc
me/mwking/lipid-synthesis.htmlphospholipids (Jan
2007)
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Glycolipids

1. always contein a ceramide
2. are found on the cell surface
3. have an amphipatic structure
4. are synthetized in a cytoplasm

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Glycolipids

1. always contein a ceramide
2. are found on the cell surface
3. have an amphipatic structure
4. are synthetized in a cytoplasm