tver state medical university · 2018. 10. 8. · tver state medical university biochemistry...
TRANSCRIPT
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).