Post on 22-Sep-2020
TVER STATE
MEDICAL UNIVERSITY
BIOCHEMISTRY DEPARTMENT
CHEMISTRY AND METABOLISM OF CARBOHYDRATES
ILLUSTRATED BIOCHEMISTRY
Schemes, formulas, terms and algorithm of preparation
The manual for making notes of
lectures and preparation for classes
Tver, 2018
2
Carbohydrates ( glycerides ) are called: Cn(H2O)m; except of (dioxyribose, etc.);
Polyhydroaldehydes ( aldoalcohols);
Polyhydrooxyketone ( ketoalcohols);
Their derivatives and polymers consisting of them.
Classification of carbohydrates (basic representation)
Polymers with the degree of polymerisation <10 are called as……………...(?) , >10……………(?)
— monosaccharides;
— disaccharides;
— oligosaccharides;
— polysaccharides;
Representatives of certainl classes of carbohydrates (choose and call examples according to the clas-
sification):
1) Glycerol aldehyde
2) Dioxyacetone
3) Erythose
4) Ribose
5) Dioxyribose
6) Ribose
7) Glucose
8) Mannose
9) Galactose
10) Fructose
11) Maltose (–1,4)
12) Isomaltose (–1,6)
13) Lactose
14) Succrose
15) Starch
16) Glycogen
17) Cellulose
Carbohydrates
oligosaccharides
(disaccharides)
Hexoses
Monosaccharides polysaccharides
Aldoses Ketoses
Trioses
Tetroses
Pentoses
Maltose (iso-
maltose)
Succrose
Lactose
homopolysaccharides Heteropolysaccharides (Glycoaminoglycanes)
Starch Cellulose
Glycogen
Hyalo-
lurnic
acid
Derma-
tasulphates
chondroitin-
sulphates and
others.
3
18) Hyalolurnic acid
19) Chondroitinsulphate
20) Dermatasulphates and others
reduction oxidation
5
4
3 2
1
O
OH
OH
OH
H
H
H
OH
H
CООН
Hexoses С6(Н2О)6
Aldose
C
CH2OH
H OH
OH
C
CH2OH
CH2OH
OC
C H2OH
O H H C *
H
C H2OH
OH C *
Which group of atoms shows what class the carbohydrate belongs to: – Aldose;
– Ketoses;
– asymmetric atom of carbon (*);
– isomer D–row;
– isomer L–row;
– formulae Collie–Toluene and Chores:
– D– glucopyranose;
– D – glucopyranose;
– hydroxysemiaccetal.
O O H
H
H
O H H
O H
H
O H
C H2ОН
O H
ОH
H
OHH
OH
H
OH
CH2ОН
I
I
I
Structure of monosaccharides
Сm(H2O)n
*
* β α
D L
4
Show:
– D– fructose;
– β-D – fructofuranose;
– α-D – fructofuranose;
6
5
4 3
2
1
O
H
H
CН2ОН
CН2ОН
OH
OH
OH
H
Ketones
6
5
4 3
2
1 O
H
H
CН2ОН
ОН
CН2ОН
OH
OH
H
Aldoses Ketoses
Pentoses С5(Н2О)5
Write the formula and explain how
the following aldoses are differ in their
structures and their derivatives:
– D– glucose.
– gluconic acid;
– glucoronic acid;
– sorbit;
– D – galactose;
– D – galactopyranose;
6
5
4
3 2
1
O
OH
OH H
H
CН2ОН
OH
H
OH
H
СН2ОН
5
5
4
3 2
1
O OH
OHOH
H
HH
H
CН2ОН
5
4
3
2
1
O OH
OH
H
HH
H
CН2ОН
H
Show:
– D– ribose;
– D – deoxyribose;
– D– ribulose;
– D– xylulose;
– -D– ribofuranose;
– -D – dioxyribofuranose.
6
5
4
3 2
1
OOH
OH
OH
NH2
H
H
H
H
CН2ОН
6
5
4
3 2
1
O
OH
NH2
H
H
CН2ОН
OH
OH H
H
Dissimilation of productivity of monosaccharides
in the human organism
6
5
4 3
2
1
O
H
CН2ОРOH
OH
H
H
CН2ОН
OH
6
5 4
3 2
1
O
OH
OH
OH
OH
CН2ОР
H
H
H
H1)
2)
6
5
4 3
2
1
O
H
CН2ОР OH
OH
H
H
CН2ОР
OH
5
4
3 2
1
O
H
CН2ОР OH
OH
H
H
H
OH
3)
4)
5)
6)
Show the formula:
– -D – glucose – 6– phosphate;
– fructose – 1,6– diphosphate.
– -D– glucosamine;
– β-D – fructose – 6– phosphate;
– -D – ribose – 5 – phosphate;
– α-D– galatosamine;
НО Н
6
1) Name and show disaccharides, explain their components
and the type of bond:
– 1 – 2,
– 1 – 4,
– 1– 4 у:
– maltose;
– lactose;
– sucrose. 2) Show disaccharides with the properties of their components
Disaccharides С12(Н2О)11
1– 4
Homopolysaccharides (С6(Н2О)5) n
Show:
– the place of aminopectane mole-
cule;
– the place of amylose molecule;
– the place of cellulose molecule ;
From which fragments glycogen and starch are formed; how do they differ?
From which fragments cellulose is formed?
– What are the types of bonds in homopolysaccharides molecules ?
Scheme of carbohydrates structure
1–4
1– 6
n
n
Cellulose Starch
Glycogen
1–4
7
Hydrolysis of carbohydrates in the gastrointestinal tract (GIT)
Section of GIT Enzymes and optimum of
рН environment Localization of enzymes Products of hydrolysis
Oral region amylase
рН≈7
Saliva 1,0-1,5 lit/day dextrin
Stomach рН=1,5-2,0 Gastric juice 2-3 lit/day —
Deudodenum amylase,
рН=7,5-8,5
pancreatic juice 1-2 lit/day disaccharide
(maltose)
Small intestine maltase,
oligo(amino)-1,6-glicosides ,
sucrose, lactase
рН=6,5-7,8
Brush margin and mucous
membrane cells monosaccharide
Products of hydrolysis:
– dextrins (amylodextrins, erythrodextrins, maltodextrins),
– maltose,
– galactose,
– glucose,
– fructose.
Carbohydrtes which are not hydrolysed in GIT (cellulose, pectins, lignins).
Biological role of cellulose
– bacteria lmedium;
– intestinal peristalsis;
– the basis of feces;
– sorbent of different toxins;
— Call the components, which are necessary for the monosaccharides absorption from the intes-tinal cavity (protein-carriers, Na
+/К
+-АТPase, energy ATP).
— Which monosaccharide is absorbed more rapidly(galactose, glucose, the fructose )? — Explain the term “symport”? — What is the energy of ATP utilised for (for bringing Na
+ from the cytoplasm of the cell)?
— By what mechanism are monosaccharides transferred from the intestine to blood?
Scheme of monosaccharides
absorption (symport)
Na-K-AТPase
8
– simple diffusion? - facilitated diffusion -symport
- active transport
- endocytosis
Functions of carbohydrates:
- Energetic (manufacture of ATP and others macroergs, heat);
- Receptative (glycoproteides of membranes);
- Protective (antibodies – Immunoglobins)
- Antigenic (glycoprotenic of erthryocytes define the group of blood);
- Plastic (elements in the structure of DNA, RNA, NAD(P), cAMP , FAD ,Co A , etc.)
- Structural (glycoaminoglycans of connective tissues);
- Antitoxic (UDP- gluconorides).
1) From what sources is glucose of blood supplied (carbohydrates of food, gluconeogenesis and glyco-
gen)?
2) What are variants of using glucose by a cell of an animal tissues (for plastic, energetic purposes
and creation of energy depot)?
DNA and RNA
The general scheme of glucose metabolism
glucose
Carbohydrates of food
Aminoacids,pyruvates,glyserine
and others (gluconeogenesis)
Lipids(TG)
Replacable amino
acids
Derivatives of
monosaccharides
heteropolysaccharides
pentose
Sou
rces
of
ente
ry
Ways
o
f
Use
s CAC
Acetyl-CoA
Macroergs (ATP)
and other types of
energy
1
2
3
4
5 6
7 8
10 glycogen
Manufacture of other
carbohydrates
9
9
Transformations of monosugars
ENZYMES
– galactokinase(Е1),
– hexoso-1-phosphate -uridiltransferase(Е2),
– phosphoglucomutase (Е3),
– glucose-6-phosphate (Е4),
– epimerase (Е5),
– galacto-1phosphate-uridiltransferase (Е6).
What are the reasons of galactozimia?(lack Е2 –hexose-1-phosphate-uridiltransferase, symptoms -
page 22-23)
ENZYMES:
– fructokinase(Е1);
– ketose-1-phosphatealdose(Е2);
–hexokinase (Е3);
– hexophosphateisomerase(Е4),
–glucose-6-phophates, (Е5),
–phosphofructokinase(Е6).
UDP-glucose
UDP-galactose
galactose
Galactose-1-phosphate
АТP
АDP
Glucose-1-phosphate
Glucose-6-phosphate
glucose
Е1
Е2
Е3
Е4
Fructose-1,6-
diphosphate
ADP
ATP
Fructose-6-phosphate
Glucose-6-phosphate glycolysis
Е5
Е4
Е3
Fructose-1-phosphate
dihydrooxyace-
tone D-glyceraldehyde
Е1
Е2
Е5
?
А (newborn before 3–4 months)
B (alternative way in adults)
UTP
UDP
Е6
UDP-galactose
Е5
UDP-glucose
pyrophosphate
Glucose-1-phosphate Е3
fructose А
(in liver)
B
(In muscular,
fatty tissues and in kidneys)
( it is not blocked
by glucose)
Е6
Are included in glucose metabolism
!
glucose
glycogen
10
- Which of the ways is not blocked by glucose and is very important for patients suffering diabetes
(way А)?
- What is the occurrence of fructosuria connected with? (lack Е1 - fructokinase, serious consequences
are not observed)?
- What are the reasons and consequences of fructose intolerance (lack Е2 – keto-1-phosphataldosase,
accumulation of fructoso-1-phosphate, symptoms - page 22-23)?
SYNTHESIS OF GLYCOGEN
1) Where is glycogen accumulated in the organism?
а) More quickly? (Liver);
b) In the greatest amount? (skeletal muscles);
Biological role of this process (the storage of easily mobilized energy).
The scheme of glycogen synthesis
2) Show on the scheme the place of action of the mentioned enzymes:
- hexokinase - Е1;
- phosphoglucomutase - Е2;
- hexoso-1-phosphat-uridintransferase - Е3;
- glycogensynthetase - Е4;
- glycogen branching enzyme - Е5.
3) What hormones stimulate (insulin), and inhibit (glucogon, adrenaline) glycogen synthesis?
Glucose-1-phosphate
Glucose
ATP
ADP
Glucose-6-phosphate
UDP-glucose
Glycogen [С6(Н2О)5] n
Glycogen [С6(Н2О)5] n+1
UDP ATP
ADP UTP
Н3РО4
II stage
I stage
Е1
Е2
Е3
Е4
(α–1,4–glycosidic bonds)
Е5
α–1,6– glycosidic bonds
11
Mobilization of glycogen (glycogenelysis). (cascade mechanism)
- Biological sense of the cascade of chemical glycolysis reactions (it reminds a chain cascade reaction
when 1 molecule of a hormone is capable to activate much amount of phosphorylase molecules).
- What is the difference between mobilization of glycogen in the liver and skeletal muscles?
- What is the role of glucose-6-phosphate (Е2) presence in the liver (formationand an output of free
glucose into blood)?
- What significance has glucose-6-phosphate (Е2) absence in muscles? (producing energy necessary
for contraction of skeletal muscles in urgent situations)?
- What hormones activate (glucogon, adrenaline) and inhibit (insulin) disintegration glucogon?
- How does disintegration glycogen in a gastroenteric tract differ from that in tissues (hydrolysis -
phosphorylase)?
glucose
(in liver)
Glucose-6-phosphate
Adrenalin
glucogon
adenalicycliase
ATP cАМР
рр1 Proteokinase
(–) proteokinase
(+)
Р1
Kinase phos-
phrylase
(–)
Kinase phos-
phrylase
(+)
ADP АТР
4 Р
4 АТР
Phosphrylase b
(–)
Phosphrylase а
(+)
4 ADP
glycogen Glucose-1-phosphate
Е1
Е2
Cell membrane receptor
Н3РО4
glycolysis
(in muscles)
12
17
Reactions of II and III stages of glucose aerobic oxidation by a dichotomic way Oxidative decarboxylation of pyruvic acid (II stages of glucose aerobic oxidation )
2 FADH
Coenzymes and vitamins: –TPP(В1), thiaminpyrophos-
phate,
–LA(N), lipoic acid,
– Н–S–CоА (В3),
–FAD (В2),
–NAD (РР).
Enzymes of the II stage:
pyruvatedehydrogenase complex:
Е1 – pyruvatedehydrogenase (reaction 1),
Е2 – dihydrolipoyl transacetylase (reactions 2
and 3).
Е2 – dihydrolipoyl dehydrogenase (reactions 4
and 5).
III stage
The chain of biological oxidation
3
АТP
2
АТP 3
АТP
3
АТP
Е
1
Е
2
Е
3
Е
4
Е
5 Е
6
Е
7
Е
8
Enzymes of the III stage:
Е1 –citrate synthetase;
Е2 - aconitase;
Е3 – isocitrate dehydrogenase;
Е4 - a-ketoglutrate dehydrogenase
complex *;
Е5 - succinyl-CоА-synthetase (succin-
ate thiokinase);
Е6 – succinate dehydrogease;
Е7 - fumarase;
Е8 – malate dehydrogenase;
* It is similar in the structure and catalytic
reactions to pyruvatedehydrogenase complex
2
1
АТP 2
TOTAL: 6 + 24 АТP = 30 АТP
3
П П 1
Н
-
4
5
2
2
2
2
3
2 х
3
2
NAD
The chain of biological oxida-
tion
2
FADH2
2
FADH
F
AD
LA E
LA
E
TPP
(B1) TPP∙
E1
ATP
2NAD →2NADH2 →
12
Catabolism of carbohydrates
Аerobic ( + О2) Аnaerobic ( – О2)
apotomic d i с h o t o m i c
Pentosephosphate way:
Аerobic glycolysis А n a e r o b i c g l y c o l y s i s
b
Biological significance:
О2
Е
2
Е Е1 glucose
glycogen
glucose–1-phosphate
Glucose-6-
phosphate
I. oxidizing stage
hexos-
es
2
NADPН2
pen-
toses
II. nonoxidizing stage
S
T
A
G
E
I
I
s т а g
а e
s т аg g e
Formation of trioses
Formation of pyruvates
ADP ATP
N
AD
NAD
Н2
lactate Korri
Cycle Stage II Formation of Acetyl - CоA
Stage III CA
C
The chain of biological oxida-
tion
Respiratory
Chain Н2О
NADН2
N
AD
О2
13
Chemical reactions of the I stage
(a dichotomizing way of glucose oxidation )
glycolysis (glycogenelysis)
Enzymes :
Stage B
Stage A
Е
* *
-
АТP
-
ATP
Н О
\ //С|
Н – С – ОН ОН| /
СН2О – Р = О\ОН
Е
5
OH
/СН2–О–Р=О| \
СН–ОН ОН|
С/ \\Н О
Н3РО4
Н–S–Е6НАД
S–Е6НАД Н2
2* Е
10
2
АDP
2 АТP
Substrate :
I
step
gly
cogen
N
AD
NAD
H2
2
ATP
2
ADP
21
Glycolysis (scheme)
Glycolysis is a sequence of fermentative reactions passing through the stage of glucose transformation in-
to pyruvate with the formation of АТP.
Complete the following determination:
Aerobic glycolysis is _.
Anaerobic glycolysis is __
Glycogenelysis is _..
Pecularities of the I stage of glucose catabolizm and biological sense of reactions of stage A and B. Call and show
them on the scheme (page 14,15):
Ste
p-1
Sta
ge
A
Sta
ge
B
1. Significance of glucose - 6 – phosphate formation Starting enzymes in the liver (glucokinese) and in muscles (hexokinese)
Km and biological value (see enzymes, page ) their.
Glucose - 6 - phosphate formation a trap for glucose (the output of glucose - 6 - phosphate from a cell
through the membrane is impossible)
2. Key (regulator) enzymes of dichotomizing way of disintegration (Е3, Е10)
3. Charge АТP: reactions 1, 3
4. Formation of АТP:
in anaerobic conditions of reactions 7, 10 (reactions of substrate phosphorylation)
in aerobic conditions of reaction 7, 10 (reactions of substrate of phosphrylation) and oxidation of NАDН2
(from the reaction 6) in the chain of biological oxidation 5. Rate regulation of the I stage by changing activity of enzymes: Е2 (PFK), Е10 (PK)
- activators of enzymes - АMP, ADP
- inhibitor of enzymes - АТP, cytrate, Acetyl-CoA and HFA 6. Convertible and irreversible reactions of A and B glycolysis stages (call enzymes).
7. Similarity and differences in reactions of the I stage of аnaerobic and aerobic ways of oxidation of glucose (variants of
NАDН2 oxidation):
- in аnaerobic conditions: oxidation of NАDН2 with the help to pyruvates (reactions of glycolytic oxido reduc-
tase, Е6 and Е11).
- in anaerobic condition:
Е11(lactate dehydrogenase) - the enzyme of the final reaction of аnaerobic glycolysis
- coferments (NAD, NADН2)
- isoferments of lactate dehydrogenase (localization in tissues, activity)
- regulation of activity (retroinhibiting)
- biological role (oxidation of NADН2, necessary for the reaction 6 without participation of oxygen,
i.e. continuation of glycolysis)
15
- in aerobic conditions: shuttle mechanisms of transport of protons from NADH2 into mitochondria
into the biological oxidation where АТP synthesis by oxidizing phosphrylation occurs:
2
Н3Р
О4 Е
6
N
AD
NAD
Н2
О
Н
О
Н С Н
н С
Н
н
О
Н
О
Н
2С О Р
=
=
О С Н
н С
О
Н О
Н
2С О Р
=
О
Н
О
Н
=
О
О ~
О
Н
О
Н
=
О Р
N
AD
NAD
Н2
- glycero-phosphatic shuttle transfer mechanism of cytoplasmic NADН2 into mitochondria matrix.
1. What organs does glycerophosphate the shuttle mechanism act (in cells of skeletal muscles and the
brain)?
2. It glycerophosphate shuttle mechanism functions how many molecules of АТP may be formed at
NADH2 oxidation (2 molecules АТP why)?
16
Internal mitochondri-
al membrane Mitochondri
al matrix
cytoplasm
glucos
e
gly
col
ysi
s
NA
D+
NAD
Н2
Cyto
pla
smic
gly
crol–
3-p
hosp
hat
e
deh
ydro
gen
ase
Mito
chondrial g
lycro
l-3-p
hosp
hate
deh
ydro
gen
ase
dioxyactonephospha
te
dioxyac-
tonephosphate
glycerol-3-phosphate glycerol-3-phosphate
FAD
FADН
2
Circuit of
biological
oxidation
2
АТP
Н2С-ОН С=О Н2С-О-Р
Н2С-ОН Н-С-О-Н Н2С-О-Р
In cyto-
plasm N
AD
NA
DН2
F
AD
FA
DН2 In mitochon-
dria
- malat-asparate shuttle mechanism of transfer of cytoplasmic NADН2 into mitochondrial matrix
Malat-aspartate shuttle mechanism to carry cytoplasmic NADH in to mi-
tochondrial matrix (in the liver, kidneys)
COOH COOH
| |
C= O H O – C – H
| | +
H – C – H H – C – H
| |
COOH COOH
1. In what cells of organs does mаlat-aspartate shuttle system act? (liver, kidneys, heart)
2. In what form does oxaloacetate come back from mitochondria into cytoplasm through the mem-
brane?
3. If mаlat - аspartate shuttle mechanism functions how many molecules of АТP may be formed at
oxidation of NADH2 (3 molecules of АТP and why)?
19
NAD NAD
H2
NAD
H2 NAD
Cytoplasm
Mitochondria
- Pasteur effect: suppression of glycolysis by respiration (changing of аnaerobic ways into aerobic in the
presence of О2)
— Cori Cycle (lactat pyruvate glucose)
- Rate regulation of the II stage of oxidation of glucose - oxidizing decarboxylation of
pyruvic acid (enzymes, vitamins, coferments: NAD / NADН2, О2).
- Rate regulation of the III stage of oxidation (CAC) (substrata: Acetyl – CоA, oxaloacetate;
enzymes, coferments, vitamins). - Association of aerobic oxidation rate of glucose with the respiratory chain and the presence of О2.
Energy balance of glycolysis and glycogenelysis in аnaerobic and aerobic conditions
* depending on the shuttle mechanism: 2 or 3 АТP
20
Gluconeogenesis (biosynthesis 80g glucose/day) It is biosynthesis of glucose from non-carbohydrate components (amino acids, glycerin, lactat and other organ-
ic molecules). Chemical reactions remind reverse process of glycolysis, except 3 irreversible reactions (1, 3,
10).
Tissues in which reactions of biosynthesis of glucose (the liver, kidneys, etc.) intensively occur
Stages of oxidation:
= 3٠3 АТP
= +2∙ 2 АТP
= АТP Substrate phosphory-
lation
2•
3
NAD٠Н2
FAD٠Н2
GTP
liver
= 36 – 38 АТP
mus-
cles
а)– stage — 2 АТP
б)– stage NAD٠Н2*
АТP
АТP Sudstrate phosphor-
ylation
I
stage
II
stage
III
stage
+ 2
NAD٠Н2
= — 2 АТP
= 2–3 АТP
= +2∙ АТP
= АТP
= +2∙ (3 АТP)
6 - 8
АТP
6 АТP
24 АТP
Total
:
Total:
+2∙
2 Acetyl–
CоА
glucose
2 pyruvate
С
О2
Tissues in which gluconeogenesis does not occur (muscles)
Retell according to the sheme of gluconeogensis reaction beginning with:
lactat (lactat dehydrogenase) → pyruvate → ...
alanin → pyruvate → ...
asparate → оxaloacetate
other amino acids
glycerine (,glycerolphosphatdehydrogenase).
pyruvate→ ?.
22
Аl
а
ГД
Ф
ГТФ
С
О2
Оксалоацетат
С
О2 Н3РО4
АДФ А
ТP
Ас
п
Formation of phosphoenolpyruvat from pyruvate (the scheme of I stage
gluconeogenesis reactions )
Chemical reactions: I stage of gluconeogenesis:
Enzyme (pyruvatecarboxylase (Е1), mitochondrial malat dehydrogenese(Е'), cytoplasmic malat dehy-
drogenese(Е"), phosponelpyruvatecarboxikinase(Е2))
Coferments and vitamins (carboxybiotin— vit. Н, NAD — vit. РР (B5))
Macroergs (АТP, GTP)
Using the scheme (page 22), call substrate, enzymes and products of reactions which occur only
at II and III stages of gluconeogenesis:fructose-1,6-bisphosphate (Е3), glucose-6-phosphate
(Е4).
Rate regulation of gluconeogenesis by modulators of key enzymes of gluconeogenesis (pyruva-
tecarboxylase- Е1 and fructosebisphosphate-Е3):
positive modulators (АТP, cytrate, Acetyl - CоA)
negative modulators (ADP, АМP)
23
phosphonelpy-
ruvate
py-
ruvate
cytoplasm mitochondria
С
О2 АТP
oxaloacetate
ma-
lat
АDP + Н3РО4
1
2
NADН2
NA
D+
Е
1
Е'
Е
1
Е
2
phosphonenolpyruva
te
NAD+
NADН2
GTP
GDP
malat
oxaloacetate
Е2
Е"
1 2
Е'
Н
Н -
2 2
Е
"
Е
2 С
О
ОН
~Р=О
ОН
NAD
Н2
NA
D NAD
Н2
NA
D
GT
P
Mem
bra
ne
of
mit
och
on
-
dri
a
The scheme of hormonal regulation of a carbohydrate me-
tabolism
( mainly in the liver)
The level of glucose in blood
decreases
Level of regulation of glucose
In blood
Ho
rmo
nal
Reg
ula
tion
Level of regulation of glucose
In blood
Gly
-
coly
sis
Syn
the-
sis
of
gly
co-
gen
Regulation of
Enzymes
Dis
inte
-gra
-tio
n o
f glu
.
Glu
-co
neo
-gen
esis
Regulating
enzymes
(+) (+) Hexokinase ↑
Glucokinase ↑
Phosphofructokinase
↑
Pyruvatekinase ↑
Glycogensynthetase ↑
insu
lin
( - ) ( - ) Pyruvatecarboxylase↓
Phosphonelpyruvatecar-
boxykinase ↓
fructose-1,6-bisphosphate
↓
glucose-6-phosphate ↓
phosphrylase ↓
The level of glucose in blood
increases
( - ) ( - ) Pyruvatekinase ↓
glycogensynthetase↓
glu
cogen
(+) (+) Pyruvatecarboxylase↑
Phosphonelpyruvatecar-
boxykinase ↑
fructose-1,6-bisphosphate
↑
glucose-6-phosphate ↑
phosphrylase ↑
( + ) ( - ) Pyruvatekinase ↑
glycogensynthetase ↓
Ad
ren
ali
n (+) ( + ) Pyruvatecarboxylase↑
Phosphonelpyruvatecar-
boxykinase ↑
fructose-1,6-bisphosphate
↑
glucose-6-phosphate ↑
phosphrylase ↑
( + )
Pyruvatekinase ↓
glycogensynthetase ↓
glu
coco
rtid
es (+) Pyruvatecarboxylase↑
Phosphonelpyruvatecar-
boxykinase ↑
fructose-1,6-bisphosphate
↑
glucose-6-phosphate ↑
24
The scheme of allosteric regulation of the carbohydrate
metabolism
( mainly in the liver)
Allosteric
effects of en-
zymes regu-
lation of car-
bohydrate
metabolism
gly
coly
sis
Syn
thes
is
gly
cogen
Regulating
Enzymes
Glu
con
e-ogen
esis
Regulating
Enzymes
( - ) (+) Phosphofructoki-
nase↓
pyruvatekinase↓
АТP (+)
ADP ( - ) Pyruvatecarbox-
ylase↓
(+) ( - ) Phosphofructokinase
↑
АМP ( - ) Fructose bisphos-
phate ↓
(+) Pyruvatekinase ↑ fructose-
1,6-
bisphosphate
(+) Phosphofructokinase
↑
fructose-
2,6-
bisphosphate
fructose-6-
phosphate
( - ) Fructose bisphosphate
↓
( - ) Phosphofructoki-
nase↓
Citrate
( - ) Acetyl-
CоА
(+) pyruvatecarbox-
ylase↑
( - ) Phosphofructoki-
nase↓
HFA
Ketone
bodies
25
Pentosephosphate (phosphogluconate) pathway of oxidation of carbohydrates (line,
apotomic) (scheme):
-6-phosohate Glucose-6-phosohate Glucose-6-
phosohate
6 pen-
tose
6 СО2
1 glu. 5 glu.
6 glu.
12NADP
Н2
I I
I Oxidation stage Nonoxidating
stage
2 erthyrose–4–
P
2 Fructose–6–P
I oxidazing stage
– 6
СО2 6 -pentose
(ribulose–5–p)
2 sedoheptulose–7–P
2 glyceraldehyde–3–P
(=1mole of glucose)
1
glucose
2 fructose–6–
P
II nonoxidazing stage
2 glyceraldehyde–3– P 2
5
glucose
Biosynthesis of nucleotides
and coferments
36 АТP
Biosyn-
thesisof
HFA etc..
2 6
NADPH2 6 NADP
26
Tissues in which the reactions of pentose-phosphate pathways (the liver, fatty tissue, lactating of the
mammary gland, erythrocytes) intensively occur.
I. Scheme I (oxidizing) stage PPW
II. Scheme of reactions of the II nonoxidizing stage of PPP
Retell according to the scheme on page 26 about:
- enzymes and coferments (transketolase, transaldolase, TPP - vitamin В1);
- biological significance of the II stage of PPP (regeneration of glucose from pentose);
Rate regulation of PPP: regulating enzymes (Е2, Е4), positive (NADP) and negative (NADPН2)
modulators.
NADP
NADPН2
Е
2
Е
3
Е
4
NAD
P
NADP
Н2
Е
5
Substrate: glucose, glucose-6-p, 6-phosphogluconolactane, 6-phosphogluconic acid, ribulose-5-p, xylu-
lose-5-p, ribose-5-p.
Enzymes and coferments: hexokinase, glucose-6-p dehydrogenase and
6-phosphogluconic acids, pentose-phosphateisomerase, NADP
Biological significance of the I stage of PPP oxidation of carbohydrates:
· calculate the balance of oxidation energy of 1 mole of glucose (12 NADPН2 = 12 х 3 АТP)
· list the variants of using pentose (DNA, RNA, macroergs, coferments)
· retell about the role of restored coferments (NADPН2) in the reactions of biosynthesis of HFA, choles-
trol and other lipids.
С
О2 Е
3
glucose Е
1
СН2ОН С=О НО-С-Н Н-С-ОН СН2-О-
Р=О
О
Н
О
Н
SIGNIFICANCE OF METABOLISM OF GLUCOSE IN ERYTHROCYTES:
I Glucose - the source of energy (АТP), necessary for ionic pumps (especially Na, K-АТP-ase) and
other energodependent processes.
II During glycolysis, 2,3-diphosphoglycerate-the regulator of carrying of oxygen is formed; connect-
ing with hemoglobin is reduces its affinity to oxygen and by this way makes easy to free the oxygen
in tissues;
III NADH2, formed during glycolysis is necessary for regeneration of hemoglobin from methemoglobin
by the reaction of methemoglobinreduction. Development of methemoglobinaemia may be caused
with poisoning by oxidizers, low partial pressure of the oxygen, hereditary defect of methemoglo-
binreductase and poisoning with carbonic oxide (CO).
IV High concentration of reduced glutathion is supported by reactions of the pentoso-phosphatic path
and formation of NADPH2. It is necessary for effective neutralization of active forms of oxygen in
erythrocytes.(anion of superoxides and hydrogen peroxides).
V In hereditary insufficiency , glucose-6-phosphatdehydrogenase the decrease in concentration of
NADPH2 is observed, it leads to hemolysis of erythrocytes and development of hemoliytic anemia.
DISTRUBANCES IN THE EXCHANGE OF CARBOHYDRATES.
For finding-out the reason of distrubance in the exchange of carbohydrates, more often the tests of
blood and urine of the patient are carried out, less often - bioptates of tissues for determining the content
of glucose , glycogen , lactic and pyruvic acids , insulin and also enzymes of amelases, phosphorilase,
glycogensynthetase, lactatdehydrogenase and some other enzymes in them.
Glucose of blood (plasma, serum): Limits of variation in healthy persons is 3,3-5,5 mm /l;
The increase (hyperglycaemia) and decrease (hypoglycaemia);
The reasons of changing the maintenance of glucose in blood (nonhormonal, hormonal and inheritary
due to the defect of some enzymes).
Hyperglycaemia (during the increase of glucose level in blood is higher than 10 mm / ½ glycosuria oc-
curs - loss of glucose with urine as the renal threshold for glucose does not exceed 10 mm /l in healthy
persons) Nonhormonal: alimentary, emotional, at shock, traumas of CNS, diseases of the liver, kidneys and other
kinds of pathology.
Hormonal:
In diabetes mellitus because of the deficiency of insulin and disturbance in absorption
in glucose decrease of permeability of cells membranes for glucose, decrease of catabolism of glucose
and synthesis of glycogen occur. In steroid diabetes (abundance of glucocorticoids in the blood as the result of their
hyperproduction in Chusing’s syndrome, and also by long therapy with glucocorticoidal hormones) glu-
cogenesis is increased. * In feochrmocytosis - tumors of the medullar layer of adrenal glands and as a result of
abundance of hyperproduction of adrenaline and noradrenaline the mobilization of the glycogen from
the depot increases.
* Hyperproduction of glucagon with pancreas £-cells in the presence of tumors in it leads to the mobi-
lization of glycogen from the depo.
* For finding-out the reasons of hyperglycemia and disturbance of carbohydrates, exchange and also for
defining the exact diagnosis of the disease leading to disturbance of their exchange, the patient is adminis-
tered the test for glucose tolerance (see the part of "Hormones").
* It is important to remember that the level of glucose in the blood is raised practically by all hormones,
except insulin. All this hormones decrease the level of glucose in the blood due to the increase of their
metabolism (the synthesis of glycogen increases and disintegration of glucose occurs). It is important to
remember also that hyperglycaemia occurs due to the insufficiency of insulin. During the absolute and
relative insufficiency of insulin (accordingly, I and II-type of diabetes) develop deep disturbance in car-
bohydrates, exchange and then of lipids and proteins and as a result the basic disease (diabetes) with
numerous complications develops. * The basic signs of diabetes mellitus are hyperglycaemia, glucosuria, ketonaemia and ketosis. (see
part "Hormones").
Hypoglycaemia: Nonhormonal : they are observed less often, as a rule during starvation, intensive and long physical and
intellectual loading, during the pregnancy, in weak and exhausted patients. It is important to note, that at
prematurely born after birth the level of glucose in blood can fall down to critically low value (2,0-2,5
mm / l) that is dangerous as it leads to distruction of CNS functions.
Hormonal:
They are observed at increasing in the blood, the contents of insulin as a result of hyperplasia? Of
β-cells of Langerhans’ islands in patients ill with a tumor of pancreas or in over dosage of insulin
induced in therapeutic purpose.
During hypocorticoidism (Adisson’s disease, secondary insufficiency of the cortex of adrenal glands).
For diagnosis of hormonal hyper or hypoglycaemia in patients the level of hormones in serum of
blood more often insulin, glucocorticoids, adrenaline and glucogon are determined, and also the
condition of functional activity of endocrine glands is analyzed.
The contents of pyruvate in the blood of patients increases at hypovitaminosis В1 (illness of beri-
beri) more often. The level of lactate in the blood increases in healthy persons at hard physical exertion, in patients
with ischemia of organs and tissues of the most various etiology and first of all at IDH (ischemic diseases
of heart) and infarction of myocardium. The disturbance in the exchange of carbohydrates is quite often a result of changing (increase or de-
crease)in functions of enzymes. More often it is the inherited pathology caused by a mutation of genes,
coding the future protein - the enzyme. Depending on the defect of the enzyme this or that way of metab-
olism of glucose is distinguished:
A. Syndrome of malabsorbtion of carbohydrates (enzymopathy at a stage of diges-
tion or absorption more often of monosaccharids). These are hereditary autosomal-
reccesive enzymopathies, connected with the lack of Na - dependent on transport of
monosaccharids, and also the enzymes of parietal digestion;
B. Enzymopathies of interconversions of hexoses are the consequence of enzymes de-
fect and their transformations (a, b);
C. Illnesses of glycogen (hereditary disturbance of the glycogen exchange caused by in-
sufficiency or complete absence of the enzyme participating in the glycogen exchange) 1) Glycogenoses - pathology of the enzymes participating in glycogen disintegration (phosphorylases,
etc.).
2) Аglucogenoses - pathology of the enzymes participating in the glycogen synthesis (glycogensynthe-
tases).
D. Glycosidoses - diseases connected with the defect of glycosidase - the enzymes destroying
heteropolysaccharids.
The most widespread enzymopathies (names of diseases, the reasons and biochemical conse-
quences, symptomatology and treatment): The name of diseases, reasons and 'biochemical consequences (•) symptomatology recommended
treatment .
A. 1) Congenital intolerance of lactose in children. ¦ the congenital pathology of develop-
ment(manufacture) of lactase: unhydrolated lactose is fermented by the enzymes of intestinal flora with
the formation of much СО2 and organic acids: hyperosmosity, decrease in reception of lactose products
of digestion (glucoses and galactoses) in the blood and tissues. Meteorism, intestinal colics, diarrhea, and
as a consequence- intoxication of the organism. It is caused by mother milk. Secondary hypotrophy.
Transfer of newborns on artificial feeding.
A2) Lactose intolerance. ¦ gastro - intestinal diseases, and also after the resection of the stomach.
Меteorism, pains in the stomach, diarrhea after taking milk. Temporary discontinuance of taking milk in
the diet.
A 3) Lactose intolerance in adults (in 20-80 % of adults: Negroes, Indians, Chukchi) ¦ Deficiency
of lactase enzymes (stoppage of a lactase gene at a certain age). Меteorism , pains in the stomach, diar-
rhea after taking milk. Discontinuance of taking milk in the diet.
A 4) Saccharose intolerance ¦ Hereditary defect of the saccharase enzyme. Diarrhea after taking sac-
charase in the diet. Stoppage of taking saccharoses in the diet.
B 1) Galactosemia ¦ Insufficiency of hexo-1-uridyltransferase enzyme, that leads to: accumulation of
neutrotoxic galactos-1-phosphate and galactose, inhibition of disintegration of glycogen and pentose cy-
cle, hypoglycaemia and to the limited reception of glucose into the brain , Refuse from the meal, vomit-
ting,diarrhea, delay of growth, cataract, enlargement of the liver, jaundice, dementia. The lab data. : ga-
lactosaemia, hypoglycaemia,hyperlipidaemia. Transfer of children from breast feeding to artificial, with
the absence of galactose in it (till 3-4 months of a newborn.)
B 2) Congenital intolerance of fructose ¦ Insufficiency of fructoso-1-phosphotaldolase: ᄋ collection
of fructoso-1-phosphate, the lasts inhibit phosphorilase of glycogen and fructoso-1,6-biphosphotase. Dis-
turbances accumulation the formation of glucose from fructose, disintegration of glycogen, hypoglycae-
mia develops, Vomiting, spasms after taking food with fructose (sugar). Elimination of fructose from the
diet.
B 3)Fructosuria ¦ Insufficiency of fructokinase: ᄋ fructose does not participate in the metabolism. Ac-
cumulates in the blood and discharges with the urine. Fructosaemia, fructosuria, there are no other symp-
toms. The treatment is not necessary.
C 1) Glycogenoses- Gierke’s disease - Hers illness etc. ¦ Defective enzymes:glucoso-6-phosphate,
phosphorilase of the liver, etc. Superfluous accumulation of glycogen in various organs and tissues, often
the destruction of cells, hypoglycaemia in an empty stomach. in the blood the contents of lactate and py-
ruvate are increased. The enlargement of the liver, muscular weakness, spasms, inhibition of the growth,
acidosis, early death. Often receptions of food are recommended.
C 2) Aglycogenoses ¦ glycogensythetase defect: acute hypoglycaemia on an empty stomach because
of the lack of stocks of glycogen constant starvation of the brain. Often vomittings, spasmes, losses of
consciousness. Delay in intellectual development. Death in the early childhood. Frequency of glycoge-
netic illnesses 1:40000. Often receptions of food are recommended.
D) Glycosidoses. Lysosomal diseases of accumulation ¦ glycosidases defect the enzymes destroying
heteropolysaccharids in lysosomas. In a cell heteropolysaccharids are accumulated hepatomegalia and
splenomengalia are shown from the first weeks of the life, they are connected with acute disorders of the
development of the child. Death occurs at early age. The treatment is symptomatic.