TVER STATE

MEDICAL UNIVERSITY

BIOCHEMISTRY DEPARTMENT

CHEMISTRY AND METABOLISM OF LIPIDS

ILLUSTRATED BIOCHEMISTRY

Schemes, formulas, terms and algorithm of preparation

The manual for making notes of lectures

and preparation for classes

Tver, 2018

CHEMISTRY OF LIPIDS

1. Define: What are lipids? (chemical nature, solubility in polar and non-polar media)

2. Classification of lipids: Lipids

I Simple II Compound

1 2 3 1 2 3

1.free fatty acids

2.glycerides

ТG,DG, МG 3.wax

I. SIMPLE LIPIDS

1. Higher fatty acids (HFA ). Synonyms: free fatty acids (FFA) , non-esterified fatty

acids (NFA ).

— Define : What are HFA (number of carbon atoms(radical R) and presence of

carboxyl group):

O

R-C-OH

— Solubility of fragments of HFA in water;

— Saturated and unsaturated (mono- and polyunsaturated) HFA;

— Conformation of unsaturated (cis-, trans-form);

— Widely distributed HFA in animal tissues

С16, С18, С20, С24, С16:1, С18:1, С18:2, С18:3, С20:4.

Arachidic, arachidonic, linolenic, lignoceric, oleic, palmitoleic, stearic, linoleic, palmitic;

— Essential and non-essential HFA (essentials, vitamin F );

Biological role,

— Functions of HFA ( explain )

- Sources of energy,

- Depo of energy,

- Plastic function.

Steroids

1sterines

2 steroids

Phospholipids

1.glycerophopholipids

A. phophotides

- phophotidyl serine

- phosphotidyl ethanol

amine

- phophotidyl choline

B. plasmalogens

C.phosphotidyl inositol

D. cardiolipins

Sphingolipids

1. sphingomyeline

2. glycolipids

А.cerebrosides

B. gangliosides.

3

2. Glycerides

А. Triglycerides (ТG). Synonyms: neutral fats, triacylglycerol

Chemical composition:

— compound-ester bond (show);

— simple, mixed;

— consistency (liquid, solid, soft), depends on what;

— generic specificity (how is it determined?);

— main functions:

- Source of energy,

- Depo of energy,

- Plastic function and other functions

B. Diglycerides (DG).

C. Monoglycerides (MG).

3.Wax

— Chemical composition (the compound ester of higher fatty acids and higher

alcohol);

— Functions.

II. COMPOUND LIPIDS

1. Phospholipids.

1. Glycerophospholipids – derivatives of the phosphatidic acid (glycerol + 2 HFA + H3PO4)

A. Phosphotides

- chemical composition [phosphatidic acid + nitrogen containing

molecule (serine, ethanol amine, choline)] = phosphotidyl

choline, phosphotidyl serine, phosphatidyl ethanol amine)

O

1 ||

O CH2OH OH — C — R1

| | 2 |

R2 — C — OH HO — CH O

3| ||

CH2OH HO — C — R3

МG DG ТG

? ? ?

?

4

- schematic model of

phospholipids:

- physico-chemical properties

- functions

B. Plasmalogens (phosphatidal…)

- Difference between plasmalogens and phosphatides

(displacement of HFA in monoatomic spirit)

- functions

C. Phophatidyl inositol

- Chemical composition ( phosphatidic acid + hexa atomic cyclic alcohol

–inositol )

- functions

D. Cardiolipids

- Chemical composition ( phosphatidic acid - glycerol -

phosphatidic acid)

- functions

2. Sphingolipids

- Chemical composition (alcohol sphingosine + HFA + H3PO4 and nitrogen

containing molecule or carbohydrates, sialic acids) NH2 +

|

CH3 - (CH2)12 - CH = CH - CH - CH - СН2 – OH +

|

OH

1. sphingomyeline (Chemical composition and functions);

2. glycolipids

A. cerebrosides (Chemical composition and functions),

B. gangliosides (Chemical composition and functions).

3. Steroids

1. Sterines

— cholesterine

? ?

D C

A B

CH3

CH3

CH3

CH3

CH3

OH

cyclopentanperhydrophenanthrene nucleus

(general structural base of steroids)

5

- chemical structure,

- functions-precursors of:

a) vitamins,

b) steroid hormones,

c) membranes,

d) bile acids.

2. Sterides

- chemical composition ( cholesterol + HFA )

- functions;

Bile acids: (derivatives of cholesterol, in which the side chain is oxidized with 8-5 is

carbon atoms + hydroxyl groups + reduction of the double bond)

cholic (3, 7, 12)

chenodeoxycholic (3, 7)

deoxycholic (3, 12)

lithocholic (3)

paired bile acids

[bile acid + glycocol (glycine) or taurine]

H2N - CH2 - COOH

H2N - CH2 - CH2 - SO3H

functions of bile acids (emulsification of lipids, transport of HFA)

— reasons of slow digestion of lipids in non-emulsified form ;

— mechanisms of increasing the speed of digestion of lipids under the

action of emulsificators.

DIGESTION (HYDROLYSIS) OF LIPIDS IN GASTRO-INTESTINAL TRACT

— significance of digestion (hydrolysis) of lipids;

generic specificity of lipids;

— mechanism of hydrolysis

— the place of digestion;

— conditions of digestion

рН (role of bicarbonates);

emulsification (role of bile acids, bicarbonates and protein);

hydrolytic enzymes for lipids(proenzymes and prolipase, phospholipase A, B,

C, D; cholesterolesterase: the place of their synthesis and methods of their

activation)

6

absorption of end products of hydrolysis:

- hydrophilic;

- hydrophobic (formation of micelles);

- destiny of bile acids (entero-hepatic circulation):

1.cholesterol is absorbed with HFA by the epithelium of the intestine- recirculation (? %);

2. they are excreted with feces (? %).

Е ? 1 ? 2 ?

esters of cholesterol

CH3

CH3

CH3

CH3

CH3

O

OH OCR

PL

7

Resynthesis of lipids

— biological role;

— place of reactions;

— molecules, precursors for resynthesis and their sources;

— scheme of resynthesis (see page. 8):

Explain according to the scheme:

1. the mechanisms of activation of glycerin, HFA, nitrogen containing molecules

and their formation:

- glycerol-3-phosphate

- acyl-CoA

- choline phosphate

- CDP-choline

2. mechanisms of formation of :

- phosphotidic acid;

- diglyceride,

- triglyceride,

- lecithin (phosphatidyl choline) and other phospholipids.

8

I

II

III

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH O

| ||

CH2 — O — P — OH

|

OH

-2 HS- CoA + CТP

- PP

II

-АТP - 2АТP

+ 2 HS -CoA

CH2OH

|

HO – CH O

| ||

CH2 — O — P — OH

|

OH

CDP — O — CH2 — CH2 — N ≡ (CH3)3

O

||

R — C — S CoA

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH

|

CH2 — OН

- H3PO4

Pro

du

cts

of

dig

esti

on

wh

ich

are

ab

sorb

ed i

n

the

inte

stin

e всо

савш

иес

я в

ки

шеч

ни

ке

Pro

du

cts

of

resy

nth

esis

Act

ivat

ion

of

mo

lecu

le

I CH2OH

|

HO — CH

|

CH2OH

O

||

2 R — C — OH

?

Pro

du

cts

of

dig

esti

on

,wh

ich

are

abso

rbed

in

the

inte

stin

e

HO — CH2 — CH2 — N ≡ (CH3)3 ? ?

O

||

HO— P— O — CH2 — CH2 — N ≡ (CH3)3 | OH

O CH2 — OH

| | |

R2 — C — O — CH

|

CH2 — OН

O || O CH2 — O — C – R1 | | | R2 – C – O – CH O | ||

CH2 – O – P – O – CH2 – CH2 – N ≡ (CH3)3

| OH

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH O

| ||

CH2 — O — C — R3

O

||

R3 — C — S CoA

O

||

R — C — S CoA

O

||

R — C — OH

+ 2 HS - KoA

-АТФ Activation of molecule

- АТP

9

TRANSPORT OF LIPIDS IN THE WATER MEDIUM OF BLOOD SERUM

— Formation of lipid-protein complexes (scheme of the lipoprotein structure ):

— lipoprotein complexes, which are formed in the tunica mucosa of the small intestine

(CM,VLDL):

lipids carried by them (which lipids, their sources?),

agents for the transport of lipoprotein complexes;

— lipoprotein in the blood serum, biological role of each of the lipoproteins (details in

the theme see “compound proteins”);

— transport of lipids from the blood serum through the cytoplasmic membrane into the

cells of different organs and tissues;

The role of endothelial lipoproteinlipase in the capillaries of different tissues;

The role of receptors to lipoproteins and the mechanism of endocytosis.

CATABOLISM OF LIPIDS

1. Biological importance of the catabolism of lipids.

2. Lipolysis (mobilization of lipids from the adipose tissues [scheme, page 10])

— Importance of the process,

— Conditions for the mobilization of lipids from the adipose tissues(stress and

starvation);

— Regulating enzymes,

— Mechanism of the activation of enzymes (hormones-receptor-adenelate

cyclase- cAMP-proteinkinase-triglyceridelypase),

— Products of lipolysis of TG in the adipose tissues,

— Hormones, stimulating or inhibiting lipolysis (adrenaline, glucagons, insulin)

10

3. Oxidation of fatty acids (-oxidation): — localization of the process,

— activation of free fatty acids,

— mechanism of transport of fatty acid through the mitochondrial membrane

O

||

R — C — OH

HFA oxidation reaction (-oxidation)

Hepatocytes and different cells

СО2 + Н2О + АТP

O

||

O CH2 — O — C – R1

| | |

R2 — C — O — CH O

| ||

CH2 — O — C – R3

Е1, E2, E3 +

Complex with albumin Blood

CH2OH

|

HO — CH

|

CH2OH

O

||

3 R — C — OH ? ?

Adepocytes

+

O

||

R — C — S CoA

O

\\

C – CH2 – CH – CH2 – N ≡ (CH3)3

/

ОН

O ||

R — C — O

-oxidation

Mitochondria

HS - CoA +

O

\\

C – CH2 – CH – CH2 – N ≡ (CH3)3

/ |

ОН OH

Е2

O

\\

C – CH2 – CH – CH2 – N ≡ (CH3)3

/

ОН

O ||

R — C — O

HS - CoA +

+

Cytoplsam

O ||

R — C — S CoA

O

\\

C – CH2 – CH – CH2 – N ≡ (CH3)3

/ |

HO OH

Е1

11

- carnitine acyl transferase I

- carnitine acyl transferase II

- coenzymes(1,2),

— stages of oxidation of higher fatty acids:

I. -oxidation,

II. oxidation of acetyl-CоА in TCA,

— Development of decoding of the mechanism of -oxidation by F Knoop,

1)

?

2)

?

— Benzoic acid

— Phenylacetic acid

— Why is the process called -oxidation?

— Mechanism of -oxidation ( - 2 Н, + Н2О, - 2 Н, - 2С-fragment)

— Energy balance in I stage [х * (FADН2 + NADН2)] = ? АТP

HC

CH

CH

CH

CH

C CH2 CH 2 CO

OH

CH2 CH2

CH

CH

CH

CH

CH

C CH2 CH2 CO

OHCH2 CH2 CH2

12

— Enzymes of -oxidation:

- acyl-CоА-dehydrogenase

- enoyl-CоА-hydratase

3 NADН2

= 1 FADН2 х8

1 GTP

ETС

TCA СО2

? АТP

Н2О

½ О2 Н

+ НS - KoA

-ketoacyl - CоА

-hydroxyacyl- CоА

O

//

H3C - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - CH2 - C

\

S - CoA

7

5

6

4

3

2

1

Acyl CоА (С16)

Е - FAD Е - FADН2 ETS

Enoul- CоА

+ Н2О

Е - NAD Е - NADН2 =? АТP

ETS

-Acyl - CоА (C16 - 2) Acetyl-CоА 8х Possibility of

biosynthesis of

ketone body in

the liver

Blood

Oxidation of

ketone body in

muscles and other

organs

Total ATP = ?

Е - FADН2 ? АТP

Е -NADН2 ? АТP х7

I stage

II stage

= ? АТP

O // R – CH = CH – C \ S CoA

O // R – CH – CH2 – C | \ OH S CoA

O // R – C – CH2 – C || \ O S CoA

13

- hydroxyacyl-CоА-dehydrogenase

- thiolase

— energy balance in the oxidation of palmitic acid in I and II stages ( use the scheme)

4. Metabolism of ketone bodies (acetone bodies) A. Biosynthesis of ketone bodies

— Biological significance of biosynthesis of ketone bodies (where are they

synthesized? Where are they used?),

— Two paths of biosynthesis of ketone bodies (which is the basic),

O OH

\\ |

C - CH2 - CН - CH3

/

HO

O

||

CH3 - C - CH3

O

//

CH3 - C

\

S - CoA

O

//

H3С - C

\

S - CoA

CO2

- HS - KoA

O

//

CH3 - C

\

S - CoA O O

|| //

CH3 - C - CH2 - С - О Н

O O H О

\\ | //

C - CH2 - C - CH2 - C

/ | \

HO CH3 S - CoA

E1

НS - CоА

O O

|| //

H3C - C - CH2 - C

\

S - CoA

+

NADН2

NAD

1st pathway

basic

O

//

CH3 - C

\

S - CoA НS - CоА

2nd

pathway

E2

E3

E4

E5

14

— metabolites:

- acetyl CoA,

- acetoacetyl-CоА,

- -hydroxy--methyl glutaryl-CоА,

- acetoacetate (acetoacetic acid),

- -hydroxybutyrate (-hydroxybutyric acid),

- acetone

— enzymes:

- acetyl-CоА-acetyl-transferase;

- hydroxymethyl glutaryl- CоА -synthetase,

- hydroxymethyl glutaryl- CоА-liase,

- hydroxybutyrate dehydrogenase,

- deacylase,

B. Oxidation (utilization) of ketone bodies

— metabolites:

- -hydroxybutyrate,

- acetoacetate,

- acetyl CоА,

— enzymes:

- -hydroxybutyrate dehydrogenase,

- CоА-transferase

- thiolase

- acylCоА–synthetase

- АТP

- НS - CоА

O H O

| //

H3C - C - CH2 - C

| \

H OH

O O

|| //

H3C - C - CH2 - C

\

OH

O O

|| //

H3C - C - CH2 - C

\

S - CoA

O

//

2 CH3 - C

\

S - CoA

NAD NADН2 ? АТP

succinyl S -CоА

2nd

path

succinate

- HS - CоА

TCA СО2

? АТP

ETС Н2О

½ О2 Н

1st

path

Е1

E2

E4

E3

15

— energy balance during the oxidation of ketone bodies

— concentration of ketone bodies in plasma

- 0,2-0,6 mM/l – in normal condition,

- up to 20 mM/l – in pathological conditions (diabetes, starvation).

5. Oxidation of unsaturated fatty acids (transformation of cis- conformation into trans-

form , and then + Н2О, - 2 Н, - 2 С-fragment)

6. Oxidation of fatty acids with odd number of carbon atoms (-oxidation,acetyl-

CоА, propionyl-CоА [3 с]),

7. Regulation of -oxidation of HFA.

— Influence of malonyl-CоА on the activity of enzyme carnitine acetyl transferase.

8. Oxidation of glycerine (see page 16)

— metabolites:

- glycerol,

- glycerol phosphate,

- dioxyacetone phosphate,

- glyceraldehydes phosphate,

- diphosphoglyceric acid,

- 3-phosphoglyceric acid,

- 2- phosphoglyceric acid,

- phosphoenol pyruvate,

- pyruvic acid,

- acetyl-CоА,

— enzymes:

- glycerol kinase

- glycerol phosphate dehydrogenase

- Balance of energy during the oxidation of glycerin

- Variant of use of glycerin for biosynthesis of glucose

+ СО2 (biotin, B12)

Propionyl-CоА (3 С) succinyl-CоА (4 С) TCA АТP

E5

16

Н2О

Е

Е

Е

Е

?

?

?

- АТP

C H 2 O H

NAD

NADН2 ? АТP

NADН2 ? АТP

? АТP

? АТP

O

//

CH3 - C

\

S - CoA

NAD

NADН2 ? АТP

СО2

Dic

hoto

mic

pat

hw

ay o

f o

xid

atio

n o

f glu

cose

TCA СО2

? АТP

ETС

½ О2 Н

Е1

Е2

?

?

C H 2 O P O

O H

O H

C H 2 O H

C O

C H 2 O H

C H O H

C H 2 O P O

O H

O H

C H 2 O H

C H O H

C H 3

C O

C

O H

O

17

WAYS OF TRANSPORT, USE AND REMOVAL OF CHOLESTEROL

Transport of cholesterol of food and endogenic cholesterol to tissues

Role of VLDL and LDL (significance of lipoprotein lipase, receptors and

endocytosis during receipt of cholesterol in cells)

—

— Reverse transport of cholesterol from the tissues to the place of its use and removal

- Role of HDL and enzyme LCAT( lecithin-cholesterol-acyl-transferase)

18

Scheme of use and removal of cholesterol from an organism

UV-

radiation

Oxidation of the side

chain to 2 "С"

With food 0,5 – 1g/day Synthesis from acetyl CоА

about 1 g/day

Cholesterol of

tissues Excretion with

cutaneous fats

Желчные кислоты

calcitriol

Hormones of the

adrenal cortex Male

hormones

Female

hormones

(progesterones)

Female

hormones

(estrogenes)

Oxidation upto 17-

ketosteroids Esters with

sulphuric or

glucoronic

acid

I n l i v e r

Excretion with urine

CH3

CH3

CH3

CH3

CH3

OH

COOH

CH3

CH3

OH

CH3

OH

OH

Basic pathway

CH3

CH3

OH

CH3

O

pregnenolone

Vitamins of group D

CH3

CH2

CH3

OH

CH3

CH3

Excretion with

feces

[1]

[2]

[3] [4]

[5]

Daily requirement 1,0 – 1,5 g/day

steroid hormones

2

1

3

~ 100 mg

~ 40 mg

~ 10 mg

~ 500 mg

~ 500 mg

19

CATABOLISM OF PHOSPHOLIPIDS IN TISSUES

— phospholipase of tissues (А1, А2, С, D);

— lysolecithin, regeneration of membranes;

— use of arachidonic acid;

— -oxidation of higher fatty acids;

— oxidation of glycerin.

ANABOLISM OF LIPIDS

Biological importance of biosynthesis of lipids

HFA which can be synthesized in human tissues (С4-24).

Which fatty acids can not be synthesized in the human tissues? (С 18 : 2 , С18 : 3 , С20 : 4 ).

Biosynthesis of HFA (hight fatty acids)

— Is it a reverse path of -oxidation?

— Differences between biosynthesis and -oxidation of HFA.

—

DIFFERENCES -oxidation Biosynthesis

Place of action mitochondria cytoplasm

Coenzymes NAD, CоА, FAD ACP, NADPН2

-2 and 3 C fragments Breaking away of 2С, acetyl -CоА Increase by 2 С at the expense of malonyl

CoА

— Permeability of membranes for acetyl- CоА

— Transport of acetyl- CoA from mitochondria to the cytoplasm( explain according to the

scheme)

synthesis of fatty acids

20

Biosynthesis of HFA begins with the formation of malonyl- CoA

— Biosynthesis of malonyl-CoA.

acetyl–CоА–carboxylase

biotin(vitamin H)

— Assembling of HFA in ACP.

The scheme of the structure of multienzyme complex of fatty acid synthetase.

— Reactions of biosynthesis of fatty acids

cystein-SH

Enoyl-ACP-

reductase 3-hydroxy-

acyl-ACP-

dehydratase

3-ketoacyl-

ACP-reductase

3-ketoacyl-

ACP-

synthetase

Malonyl-

transferase Аcetyl-

transferase

Е1 Е2

Е4

Е5 Е6

ACP

Е3

+ CO2

- АТP

C H 2

C O

S CoA

C

O

O H

CН3

C

O

S CoA

E

phosphopantetein-SH

21

- metabolites:

[2]

[1] O

||

S H CoA S - C - CH3

O

||

S H CoA S - C - CH2 - COOH

[7]

[3] ACP

SH

O O

|| ||

S - C - CH2 - С - СH3

ACP

CO2

SH

O

||

S - C - CH2 - CH2 - CH3

ACP

+ NADPН2

+ NADPН2

- Н2О

ACP

And then?

[4]

[5]

[6]

О

||

S - C - CH2 - CH2 - CH3

SH

cys

PP

ACP

ACP

SH

O OH

|| |

S - C - CH2 - СH - СH3

SH

O

||

S - C - CH2 = СH2 - СH3

O

||

CoA S - C - CH2 - COOH

CO2

22

acetyl-CоА (ACP)

malonyl-CоА (ACP)

acetoacetyl-ACP

3-hydroxybutyryl-ACP

crotonyl-ACP

butyryl-ACP

— Energy expenses and the main sources of NADPН2 for the biosynthesis of

HFA(pentose phosphate pathway/hexose monophosphate sunt-HMP sunt)

— Biosynthesis of unsaturated fatty acid (acyl-CоА-oxygenase).

— Regulation of the biosynthesis rate of HFA (acetylCоА-carboxylase [(+): citrate,

ATP; (-): HFA],hormones(insulin, adrenalin, glucagon).

Biosynthesis of triglycerides and phospholipids

Biosynthesis of triglycerides

- Activation of glycerol,

— Activation of fatty acids ,

— metabolites:

- glycerol,

- dioxyacetone phosphate (DOAP),

- glycerol-3-phosphate,

23

- monoglyceride,

- phosphatidic acid,

- diglyceride,

- acyl CoА,

- triglyceride,

— enzymes:

- glycerol kinase,

- glycerol-3-phosphate dehydrogenase,

-- Features of biosynthesis of triglycerides in the liver, fatty tissues, in the

intestine wall

Biosynthesis of phospholipids (special and de novo synthesis).

— Sources of diglycerides and the nitrogen bases,

— Activation of the nitrogen bases,

— metabolites:

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH O

| ||

CH2 – O – Р – О – CH2 – CH2 – N ≡ (CH3)3

|

OH

H2N - CH2 - CH2 - OH

H2N - CH2 - CH2 - O - P

H2N - CH2 - CH2 - O - CDP

АТP

АDP

CTP

РР

CMP

(СН3)3N+ - CH2 - CH2 - OH

(СН3)3N+ - CH2 - CH2 - O - P

(СН3)3N+ - CH2 - CH2 - O - CDP

CMP

АТP

ADP

CTP

РР

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH

|

CH2 — OН

O

||

O CH2 — O — C — R1

| | |

R2 — C — O — CH O

| | |

CH2 — O — Р – О – CH2 – CH2 – NH2

|

OH

3 (- СН3)

Where and

which

variant is ?

СН3 | S+ —

| CH2 |

CH2 | CH — NH2

| COOH

|

I II

adenosyl

serine

24

- serine, ethanol amine, choline, and methionine

- phosphoethanol amine, and phosphocholine,

- CDP-ethanol amine and CDP-choline,

- Phosphatidyl ethanol amine and phophatidyl choline,

- donors of methyl groups (s – adenosyl methionine and others)

— lipotropic factors( choline, ethanol amine, inositol, methionine, pangamic acid

(vitamin В15), S-methyl methionine (vitamin U), food products):

- Physiological influence on the organism,

Biosynthesis of cholesterol.

Organs in which biosynthesis of cholesterol most actively proceeds.

— metabolites:

- acetyl CoА,

- acetoacetyl CoА,

- -hydroxy--methyl-glutaryl CoА,

- mevalonate,

- isopentenyl pyrophosphate,

- squalene,

- lanosterine,

- cholesterol.

— Enzymes:

- acetyl-CoА-acetyl transferase,

- hydroxymethyl glutaryl-CoА-synthetase,

- hydroxymethyl glutaryl-CoА-reductase (HMG-CoА-reductase),

Regulation of biosynthesis of cholesterol - HMG-CoА-reductase (insulin, glucagons, cholesterol and LDLP).

PA

DG

TG PL

lipotropic

factors

Fat accumulation Biological membranes

and –LP

25

O

//

CH3 - C

\

S - CoA

O O

|| //

H3C - C - CH2 - C

\

S - CoA

O

//

CH3 - C

\

S - CoA

O

//

CH3 - C

\

S - CoA

+

HS - CoA

O OH O

\\ | //

C - CH2 - C - CH2 - C

/ | \

HO CH3 S - CoA

HS - CoA

O OH

\\ |

C - CH2 - C - CH2 - CН2 -OH

/ |

HO CH3

2 NADPН2

2 NADP

HS-CoA

Activation, decarboxylation

С(5) - Р - Р

condensation

С(30)

cyclisation

С(30)

С(6)

ATP

ADP

СО2

С(27)

CH3

CH3

CH3

CH3

CH3

OH

I

II

III

Stages:

E1

E2

E3

squalene

lanosterine

26

DISODERS OF THE LIPID METABOLISM

1. Disoders of metabolism at the stage of digestion and absorption of the products of

hydrolysis.

— deficiency of bile acids ( consequences).

— deficiency and insufficient activity of enzymes of lipids digestion (consequences).

— steatorhoea, its causes and consequences.

2. Contents of various classes of lipids in the blood serum of healthy people

GL ТG CH PL HFA VLDL LDL HDL

g/l 4,5-10,0 0,5-1,5 1,4-2,2 2,2-4,6 0,06-0,16 1,2-2,8 3,9-7,9 0,3-4,7

mM/l -- --

Before 20 years

3,1-5,8

-- 0,2-0,6 -- -- --

20-29 years 3,4-5,8

30-39 years 3,7-6,2

40-49 years 3,7-6,8

50-59 years 4,1-7,3

60-69 years 4,2-7,4

- Explain the importance of age factor, sex, region of residing and other reasons for these

indices.

- Explain the meaning or differences of the terms

hyperlipemia

hypercholesterolemia,

hypertriglyceridemia,

hyperlipoproteinemia (hyperchylomicronemia, hyper--lipoproteinemia),

dyslipoproteinemia.

3. Typing of dyslipoproteinemia according to Fredrickson (recommended by WHO)

I type IIa type IIb type III type IV type V type

CM — — — –—

VLDL (pre--LP) N N —

LDL (-LP) N — N N

Floating -LP –— –— –— –— –—

Principles of typing of dyslipoproteinemia (predominance of anyone of the classes of

LP).

Significance (for diagnosis, treatments, prophylaxis).

27

Defects of the dislipoproteinemia typing according to Fredrickson (it does not take into

consideration the role of HDL, influence of nutrition and other reasons on the contents of

lipoproteins)

4. Causes of occurrence and development of hyper- and dyslipoproteinemia.

According to the mechanism of metabolism disoders and contents of lipids they

distinguish:

A. primary (hereditary)

familial hypercholesterolemia (homo- and heterozygotic carriers of an

abnormal gene which codes a receptor to -lipoproteins, and

consequences of this pathology)

deficiency of lipoprotein lipase activity, LCAT and other proteins of

lipoprotein metabolism (chylomicronemia).

B. secondary (acquired):

alimentary

emotional (stress)

hormonal

- obesity

- diabetes melitus

- cholelithiasis

- atherosclerosis

- others (ischemia, hypoxia, hypodynamia).