Metabolism of lipids

1
Metabolism of lipids

• Vladimíra Kvasnicová

2
Lipids group of biological molecules that are
insoluble in aqueous solutionsand 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)

3
The figure was adopted from J.Koolman, K.H.Röhm
/ Color Atlas of Biochemistry, 2nd edition,
Thieme 2005
4
Structural components of lipids

• alcohols
• glycerol (a)
• sfingosine (b)
• cholesterol (c)
• inositol (d)
• long chain carboxylic acids( fatty acids)

a) b)
c) d)
The figures are adopted from http//en.wikipedia.o
rg (April 2007)
5
Free Fatty Acids(FFA)
The figure is found at http//www.tvdsb.on.ca/saun
ders/courses/online/SBI3C/Cells/Lipids.htm (Jan
2007)
6
The figure was adopted from J.Koolman, K.H.Röhm
/ Color Atlas of Biochemistry, 2nd edition,
Thieme 2005
7
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)
8
The figure is found at http//courses.cm.utexas.ed
u/archive/Spring2002/CH339K/Robertus/overheads-2/c
h11_cholesterol.jpg (Jan 2007)
9
The figure was adopted from J.Koolman, K.H.Röhm
/ Color Atlas of Biochemistry, 2nd edition,
Thieme 2005
10
Structure of phospholipid
The figure is found at http//www.mie.utoronto.ca/
labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)
11
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)
12
Choose compounds counting among lipids

1. glycerol
2. triacylglycerols
3. ketone bodies
4. cholesterol

13
Choose compounds counting among lipids

1. glycerol
2. triacylglycerols
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
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
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
19
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
20
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
21
The figure was accepted from the book Grundy,
S.M. Atlas of lipid disorders, unit 1. Gower
Medical Publishing, New York, 1990.
22
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
23
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

24
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

25
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)
26
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
27
Degradation of phospholipids (hydrolysis)
The figure is found at http//web.indstate.edu/thc
me/mwking/lipid-synthesis.htmlphospholipids (Jan
2007)
28
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)
29
?-oxidation of fatty acids (1 cycle)
dehydrogenation
The figure is found at http//www.biocarta.com/pat
hfiles/betaoxidationPathway.asp (Jan 2007)
30
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
31
Carnitine acyltransferaseregulates ?-oxidation
regulatory enzyme activation inhibition
carnitin palmitoyltransferase I (carnitin acyltransferase) malonyl-CoA( intermediate of FA synthesis)
32
Omega-oxidation of fatty acids (endoplasmic
reticulum minority pathway for long chain FA)
The figure was found at http//www.biocarta.com/pa
thfiles/omegaoxidationPathway.asp (January 2007)
33
?-oxidation of fatty acids

1. proceeds only in the liver
2. produces NADPHH
3. is localized in mitochondria
4. is activated by malonyl-CoA

34
?-oxidation of fatty acids

1. proceeds only in the liver
2. produces NADPHH
3. is localized in mitochondria
4. is activated by malonyl-CoA

35

• 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)
36

• 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/wik
i/ImageKetogenesis.png (Jan 2007)
37
Regulation of ketogenesis
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
38
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)
39
Ketone bodies

1. are synthesized from acetyl-CoA
2. are produced by muscle tissue as a consequence of
   increased fatty acid oxidation
3. serve as an energy substrate for erythrocytes
4. can be excreted with urine

40
Ketone bodies

1. are synthesized from acetyl-CoA
2. are produced by muscle tissue as a consequence of
   increased fatty acid oxidation
3. serve as an energy substrate for erythrocytes
4. can be excreted with urine

41
Fatty acid synthesis (1 cycle)
The figure is found at http//herkules.oulu.fi/isb
n9514270312/html/graphic22.png (Jan 2007)
42
activated carbon
43
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)
44
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)
45
The pathway of synthesis of fatty acids

1. produces NADPHH
2. starts by carboxylation of acetyl-CoA
   malonyl-CoA is formed
3. is localized in mitochondria
4. includes reduction steps

46
The pathway of synthesis of fatty acids

1. produces NADPHH
2. starts by carboxylation of acetyl-CoA
   malonyl-CoA is formed
3. is localized in mitochondria
4. includes reduction steps

47
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
48
Biosynthesis of triacylglycerols

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

49
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
50
Biosynthesis of cholesterol
regulatory enzyme

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

51
cholesterol synthesis
ketone bodies
The figure is found at http//amiga1.med.miami.edu
/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan
2007)
52
Synthesis of cholesterol consumes ATP
activated isoprene
The figure is found at http//www.apsu.edu/reedr/R
eed20Web20Pages/Chem204320/Lecture20Outlines/c
holesterol_synthesis.htm (Jan 2007)
53
activated isoprene two frorms
The figure is found at http//www.apsu.edu/reedr/R
eed20Web20Pages/Chem204320/Lecture20Outlines/c
holesterol_synthesis.htm (Jan 2007)
54
The figure is found at http//www.apsu.edu/reedr/R
eed20Web20Pages/Chem204320/Lecture20Outlines/c
holesterol_synthesis.htm (Jan 2007)
55
Regulation of cholesterol synthesis
regulatory enzyme activation inhibition
HMG-CoA reductase insulin, thyroxine (induction) cholesterol glucagon (repression) oxosterols (repression)
56
Cholesterol

1. is synthesized in mitochondria
2. synthesis includes the same intermediateas
   ketogenesis acetone
3. can be broken down to acetyl-CoA
4. is synthesized if the ratio insulin/glucagon is
   low

57
Cholesterol

1. is synthesized in mitochondria
2. synthesis includes the same intermediateas
   ketogenesis acetone
3. can be broken down to acetyl-CoA
4. is synthesized if the ratio insulin/glucagon is
   low