Metabolism of lipids Vladimíra Kvasnicová. Lipids = group of biological molecules that are...

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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)

• long chain carboxylic acids(= fatty acids)

The figures are adopted from http://en.wikipedia.org (April 2007)

The figure is found at http://www.tvdsb.on.ca/saunders/courses/online/SBI3C/Cells/Lipids.htm (Jan 2007)

Free Fatty Acids(FFA)

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-2/ch11_lipid-struct.jpg

(Jan 2007)

Structure of lipids

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-2/ch11_cholesterol.jpg (Jan 2007)

The figure is found at http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/3.21.jpg (Jan 2007)

Structure of

phospholipid

The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#phospholipids (Jan 2007)

sphingosine

ceramide

= amide formed from sphingosine and fatty acid

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) cholesterolAceton

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.

type source principal lipids

important apoprotei

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 chylomicronsto 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

Lipoproteins

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 is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch17_lipid-adipocytes.jpg (Jan 2007)

Releasing of freefatty acids from

TAGof fatty tissue

and their followed transport

to target cells

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 reservetriacylglycerols

activated by phosphory-lation

acidic lipase

various tissues

lysosomes hydrolysis of TAG acidic pH-optimum

Lipases

Degradation of

phospholipids

(hydrolysis)

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)

Regulation of lipolysis

The figure is found at http://www.biocarta.com/pathfiles/betaoxidationPathway.asp (Jan 2007)

-oxidation of fatty acids (1 cycle)

dehydrogenation

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

Transport of fatty acids

into a mitochondrio

CARNITIN TRANSPORTE

cytoplasm

Carnitine acyltransferaseregulates -oxidation

regulatory enzyme activation

inhibition

carnitinpalmitoyltransferase

I(carnitin

acyltransferase)

malonyl-CoA(= intermediate of FA synthesis)

The figure was found at http://www.biocarta.com/pathfiles/omegaoxidationPathway.asp (January 2007)

Omega-oxidation of fatty acids

(endoplasmic reticulum;

minority pathway for long chain

-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+

d) is activated by malonyl-CoA

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 Acetyl-CoA

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: mitochondriaHMG-CoA is formed

also in a cytoplasm during cholesterol

synthesis !

Acetyl-CoA

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

Regulation of ketogenesis

The figure is found at http://www.richmond.edu/~jbell2/19F18.JPG (Jan 2007)

Ketone bodies degradation(oxidation)

proceeds during starvation in

extrahepatic tissuesas an alternative

energy source

(in a brain as well)

Citratecycle

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

The figure is found at http://herkules.oulu.fi/isbn9514270312/html/graphic22.png (Jan 2007)

Fatty acid synthesis

(1 cycle)

„activated carbon“

The figure is found at http://web.indstate.edu/thcme/mwking/lipid-synthesis.html#synthesis (Jan 2007)

Transport of acetyl-CoA from a mitochondrion to the cytoplasm

FA synthesis

NADPHfrom pentose

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)

Regulation of fatty acid synthesis

The pathway of synthesis of fatty acids

a) produces NADPH+H+

b) starts by carboxylation of acetyl-CoA: malonyl-CoA is formed

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

d) includes reduction steps

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

Comparision of fatty acid synthesis and degradation

Biosynthesis of triacylglycerols

phosphatidic acid phosphatase

steroid hormones (induction)

lipoprotein lipase(important for storage of TAG in a fatty tissue)

insulin apolipoprotein C-II

Regulation of TAG metabolism

Biosynthesis of cholesterol

The figure is found at http://web.indstate.edu/thcme/mwking/cholesterol.html (Jan 2007)

regulatory enzyme

The figure is found at http://amiga1.med.miami.edu/Medical/Ahmad/Figures/Lecture9/Slide23.jpg (Jan 2007)

cholesterol synthesis

ketone bodies

The figure is found at http://www.apsu.edu/reedr/Reed%20Web%20Pages/Chem%204320/Lecture%20Outlines/cholesterol_synthesis.htm (Jan 2007)

activated isopreneSynthesis of

cholesterol consumes ATP

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)

regulatory enzyme

activation inhibition

HMG-CoA reductase

insulin, thyroxine (induction)

cholesterol glucagon (repression) oxosterols (repression)

Regulation of cholesterol synthesis

Cholesterol

a) is synthesized in mitochondria

b) synthesis includes the same intermediateas 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 intermediateas ketogenesis: acetone

c) can be broken down to acetyl-CoA

d) is synthesized if the ratio insulin/glucagon is low

Metabolism of lipids Vladimíra Kvasnicová. Lipids = group of biological molecules that are...

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