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.