1
Ó Department of Biochemistry 2013 (E.T.)
The pentose phosphate pathway.
 Metabolism of fructose and galactose.
The uronic acid pathway.
The synthesis of amino sugars and
glycosyl donors in glycoprotein synthesis.

2
Significance of pentose phosphate pathway
• source of NADPH   (reductive syntheses, oxygenases with mixed function, reduction of glutathion)
• as a source of ribose-5-P (nucleic acids, nucleotides)
• metabolic use of five carbon sugars obtained from the diet
No ATP is directly consumed or produced

3
The pentose phosphate pathway
(Hexose monophosphate shunt)
Cell location: cytoplasma
Tissue location:
liver, adipose tissue (up to 50% of glucose metab.), erythrocytes, adrenal gland, mammary gland,
testes, ovary etc.
(generally tissues, where the reductive syntheses or hydroxylations catalyzed by monooxygenases
occur)
The other tissues use only some reactions of pentose phosphate pathway

4
Two phases of pentose phosphate pathway
Oxidative phase         irreversible reactions
synthesis of NADPH and pentoses
Nonoxidative (interconversion) phase        reversible reactions
conversion of remaining pentoses to glucose

5
Oxidative part of pentose phosphate pathway
lactonase
6-phosphogluconate dehydrogenase
glucose-6-P
NADP+
NADPH + H+
6-phosphoglucono d-lactone
NADP+
NADPH + H+
Ribulose-5-P  +  CO2
6-phosphogluconate
glucose-6-P-dehydrogenase
Glucose 6-phosphate dehydrogenase is the regulated key enzyme of the pathway.
Factors affecting the reaction:
inhibition by NADPH
Availability of NADP+
Induction of the enzyme by insuline

6
O
glucose-6-P
6-phosphogluconate
O
O
O
H
O
H
O
H
C
H
2
O
P
NADP+
NADPH + H+
C
O
O
-
C
C
C
C
C
O
H
H
O
H
O
H
O
P
H
H
O
H
H
H
H
O
O
H
O
H
H
C
H
2
O
P
O
H
6-phosphoglucono-d-lactone
H
H2O
Oxidative part of pentose phosphate pathway with structural formulas   – formation of
6-phosphogluconate
glucose-6-P-dehydrogenase
lactonase

7
C
O
O
-
C
C
C
C
C
O
H
H
O
H
O
H
O
P
H
H
O
H
H
H
H
H
C
C
C
C
C
O
H
O
H
O
H
O
P
H
H
H
H
H
O
NADP+
NADPH + H+
CO2
6-phosphogluconate
ribulose-5-P
Oxidative part of pentose phosphate pathway with structural formulas   – conversion of
6-phosphogluconate
6-phosphogluconate dehydrogenase

8
The yield of oxidative phase of pentose phosphate pathway:
  2 mols of NADPH
1 mol of pentose phosphate

9
Reversible nonoxidative reactions of pentose phosphate pathwayy
 3 Ribulose-5-P            2 fructose-6-P + Glyceraldehyde-3-P
What is the significance of this phase?
Some cells require many NADPH. Its production in oxidative phase is associated with formation of
large amount of pentoses, that the cell does not need. The pentoses are converted to
fructose-6-phosphate and  glyceraldehyde-3-P that are inermediates of glycolysis.
Summary equation:

10
Enzymes in reversible phase of pentose phosphate pathway
Ribose-5-P
H
C
C
C
C
C
O
H
O
H
O
H
O
P
H
H
H
H
H
O
Ribulose-5-P
Isomerase
Synthesis of nucleotides and nucleic acids
Reactions of nonoxidative phase of pentose phosphate pathway

11
Epimerase
H
C
C
C
C
C
O
H
O
H
O
H
O
P
H
H
H
H
H
O
Ribulose-5-P
Xylulose-5-P

12
Transketolase – it transfers two-carbon units
+
+
Prostetic group of transketolase: thiamine diphosphate
Xylulose -5-P
Ribose-5-P
Glyceraldehyde-3-P
Sedoheptulose-7-P
C
C
C
C
C
C
H
O
H
O
H
O
P
HO
H
H
H
H
C
O
O
H
H
H
O
H
H
H
C
C
C
C
C
O
H
O
H
O
H
O
P
H
H
H
H
H
O
5C
5C
3C
7C
+
+

13
Transaldolase – it transfers three-carbon units
C
C
C
C
C
C
H
O
H
O
H
O
P
O
H
H
H
H
C
O
O
H
H
H
O
H
H
+
Sedoheptulose-7-P
Glyceraldehyde-3-P
Erythrose-4-P
Fructose-6-P
H
C
C
C
C
C
H
O
H
O
P
H
O
H
H
C
O
O
H
H
H
O
H
H
H
+
7C
3C
4C
6C
+
+

14
Erythrose-4-P
+
Xylulose -5-P
+
Fructose-6-P
Glyceraldehyde-3-P
C
C
C
C
C
H
O
H
O
P
H
O
H
H
C
O
O
H
H
H
O
H
H
H
4C
5C
6C
3C
+
+
Transketolase – it transfers two-carbon units

15
The summary of pentose phosphate pathway
Ribulose-5-P                                    Ribose -5-P
2 Ribulose-5-P                                 2 Xylulose -5-P
Xylu-5-P  +  Rib-5-P                       Glyc-3-P  + Sed-7-P
Sed-7-P  + Glyc-3-P                        Ery-4-P  +  Fru-6-P
Xylu-5-P  + Ery-4-P                        Glyc-3-P  +  Fru-6-P
 3 Ribulose-5-P                           Glyceraldehyde-3-P  +  2 Fru-6-P
3 x 5C
3C + 2 x 6C

16
H
C
C
C
C
C
C
H
O
H
O
H
O
P
O
H
H
H
H
C
O
O
H
H
H
O
H
H
Ribulosa-5-P
Ribosa-5-P
Xylulosa-5-P
Erytrosa-4-P
Glyceraldehyd-3-P
TK
TA
TK
Xylulosa-5-P
H
C
C
C
C
C
O
H
O
H
O
H
O
P
H
H
H
H
H
O
Velké konfety
C
C
C
C
C
H
O
H
O
P
H
O
H
H
C
O
O
H
H
H
O
H
H
H
The summary of pentose phosphate pathway

17
The reactions of nonoxidative phase are reversible.
This enables that ribose-5-phosphate can be generated from intermediates of glycolytic pathway in
case when the demand for ribose for incorporation into nucleotides and nucleic acids is greater
than the need for NADPH.
Generation of ribose phosphate from intermediates of glycolysis

18
sedoheptulose-7-P  + glyceraldehyde-3-P           2 pentose phosphates
Transketolase reaction in opposite direction
fructose-6-P + glyceraldehyde-3-P          erytrosa-4-P +  xylulosa-5-P
(from glycolysis)
  erytrose-4-P + fructose-6-P            sedoheptulose-7-P
+ glyceraldehyde-3-P
Transaldolase reaction in opposite direction
Transketolase reaction in opposite direction
(from glycolysis)

19
Cellular needs dictate the direction of pentose phosphate pathway
Cellular need
Direction of pathway
NADPH only
Oxidative reactions produce NADPH, nonoxidative reactions convert ribulose 5-P to glucose 6-P to
produce more NADPH
NADPH + ribose-5-P
Oxidative reactions produce NADPH and ribulose 5-P, the isomerase converts ribulose 5-P to ribose
5-P
Ribosa-5-P only
Only the nonoxidative reactions. High NADPH inhibits glucose 6-P dehydrogenase, so transketolase
and transaldolase are used to convert fructose 6-P and glyceraldehyde 3-P to ribose 5-P
NADPH and pyruvate
Both the oxidative and nonoxidative reactions are used. The oxidative reactions generate NADPH and
ribulose 5-P, the nonoxidative reactions convert the ribulose 5-P to fructose 5-P and
glyceraldehyde 3-P, and glycolysis converts these intermediates to pyruvate

20
Most important reactions using NADPH
• reduction of oxidized glutathion
• monooxygenase reactions with cytP450
• respiratory burst in leukocytes
• reductive synthesis:
synthesis of fatty acids
elongation of fatty acids
cholesterol synthesis
nucleotide synthesis
NO synthesis from arginine

21
NADH   x    NADPH / comparision
Characteristics
NADH
NADPH
formation
Mainly in dehydrogenation reactions of substrates in catabolic processes
In dehydrogenation reactions other than catabolic
utilization
Mainly respiratory chain*
Reductive synthesis and detoxication reactions
Cannot be oxidized in resp. chain
Form that is prevailing in the cell
NAD+
NADH
* Transhydrogenase in mitochondrial membrane can catalyze transfer of H from NADH to NADP+

22
Significance of pentose phosphate pathway for red blood cells
GS-SG  +  NADPH   +  H+                       2GSH  +  NADP+
           glutathionreductase
Pentose phosphate pathway is the only source of NADPH for erc
It consumes about 5-10% of glucose in erc
NADPH is necessary for maintenance of reduced glutathione pool

23
Oxidized form of glutathione is generated during the degradation of hydrogen peroxide and organic
peroxides in red blood cells
2GSH  +  HO-OH      →    GSSG  + 2H2O
glutathionperoxidase
2GSH  +  ROOH      →    GSSG  + ROH  +  H2O
Accumulation of peroxides in the cell triggers the haemolysis

24
Deficiency of glucose 6-P dehydrogenase in red blood cells
Inherited disease
It is caused by point mutations of the gene for glucose 6-P dehydrogenase in chromosome X in some
populations ( 400 different mutations)
More than 400 milions of individuals worldwide
Erythrocytes suffer from the lack of reduced glutathione
Most individuals with the disease do not show clinical manifestations. Some patients develop
hemolytic anemia if they are treated with an oxidant grug, ingest favabeans or contract a severe
infetion (*AAA)
The highest prevalence in the Middle East, tropical Afrika and Asia, parts of Mediterranean
AAA* - antimalarials, antibiotics, antipyretics

25
Heinz bodies are present in red blood cells with glucose-6-P-dehydrogenase deficience
Deficiency of reduced glutathion results in protein damage – oxidation of sulfhydryl groups in
proteins leads to the formation of denaturated proteins that form insoluble masses (Heinz bodies)
Erytrocytes are rigid and nondeformable – they are removed from circulation by macrophages in
spleen and liver.

26
Favism
Some people with GHPD deficiency are susceptible to the fava bean (Vicia fava). Eating them results
in hemolysis.
mojo-fava-beans Image:Tuinboon bontbloeiend.jpg

27
Metabolism of fructose
CH2–OH
CH2–OH
C=O
HO–CH
CH–OH
CH–OH

28
Source fructose: sucrose from diet, fruits, honey, high fructose corn syrup*
Fructose enters most of the cells by facilitated diffusion on the  GLUT V
Sources of fructose
* High-fructose corn syrup is used as a sweetener in many  soft drinks, yogurts, saladd dressings
etc.
For thousands of years humans consumed fructose amounting to 16–20 grams per day, largely from
fresh fruits. Westernization of diets has resulted in significant increases in added fructose,
leading to typical daily consumptions amounting to 85–100 grams of fructose per day.

29
High-fructose corn syrup (commonly abbreviated HFCS) is a sweetening food ingredient produced by
adding enzymes to corn syrup, which is mostly glucose, to create fructose. The result is a cheaper
alternative to sugar that also functions as a preservative. As such, high fructose corn syrup is a
common ingredient in a variety of foods,
HFCS is in nearly everything: jelly, juice, sodas, whole-grain breads, cereals, ketchup, crackers,
yogurt, sweet pickles, applesauce, salad dressing, ice cream, cough syrup and lots more.
The biggest problem is that HFCS is being added to food items that don't normally have sugar and
that you wouldn't even describe as sweet -- crackers, for instance. So, not only are we chugging
down lots of sugars with our sodas, but your PBJ sandwich could have HFCS in each of its three
ingredients. Meal after meal, day after day, all of this extra sugar adds up, and that, and not
necessarily the qualities of HFCS itself, is likely one reason why rates for obesity and diabetes
have climbed since the introduction of HFCS.
Probably, the increase in consumption of HFCS has a temporal relation to the epidemic of obesity,
and the overconsumption of HFCS in calorically sweetened beverages may play a role in the epidemic
of obesity.
Obesity and high intake of HFCS

30
Fructose and glucose – comparison of metabolic features
glucose
fructose
Intestinal absorption
Metabolism
Half-life in blood
Place of metabolism
KM for hexokinase
KM pro fructokinase
Effect on insulin release
rapid
slower
43 min
Most of tissues
0,1 mmol/l
-

slower
more rapid
18 min
mainly liver, kidneys, enterocytes
3 mmol/l
0,5 mmol/l
       no

31
Important differences between metabolism of glucose and fructose
• fructose is metabolized mainly in liver by fructokinase
•hexokinase phosphorylates fructose only when its concentration is high
• fructose is metabolized more rapidly then fructose in the liver
•fructose do not stimulate release of insulin
•hepatic metabolism of fructose favors de novo lipogenesis.

32
Metabolismus of fructose
fructose
fructose- 1-P
fructokinase
aldolase B
Glyceraldehyde  +  dihydroxyaceton-P
Glyceraldehyde-3-P
triose-kinase
ATP
glycolysis
hexokinasa
fructoso-6-P
2
1
Conversion to glucose
ATP
 no regulation
very low KM
Most of fructose is metabolized in liver
aldolase B

33
             Aldolase A a aldolase B
• isoenzymes  (also aldolase C is known)
• aldolase A : glycolysis (cleavage of Fru 1,6-bisP)
• aldolase B: cleavage of fructose1-P
gluconeogenesis (synthesis of Fru-1,6-bisP)

34
Fructose is very rapidly metabolised in comparison with glucose.
Why ?

35
fructokinase and aldolase B (liver):
metabolismus bypasses the regulated enzymes, fructose can continuously enter the glycolytic pathway
Þ rapid degradation
J fructose is rapid, on insulin independent source of energy
L high intake of fructose results in increased production of fatty acids and consequently increased
production of triacylglycerols
L at very high fructose intake, phosphate is sequestrated in fructose -1-phosphate and synthesis of
ATP is diminished
Metabolism of fructose

36
fructose alone spikes blood sugar fairly slowly, high fructose corn syrup raises blood sugar levels
rapidly. One of the main reasons that fructose alone does not raise blood sugar levels quickly, and
therefore, is often encouraged for diabetics is that it is often eaten in its natural form in
fruits. Fruits also have fiber, which slows sugar absorption.

37
Fructose was formerly recommended as harmless sweetener replacing glucose in diabetics' diets
Current recommendations
•excessive consumption of fructose is not recommended
•a small amount of fructose, such as the amount found in most vegetables and fruits, is not a bad
Fructose and diabetics

38
Defects in metabolism of fructose
Lack of fructokinase
-     essential fructosuria
fructose accumulates in blood and is excreted into the urine
Disease is without any serious consequences.
Fructose free diet.
Diagnostics: positive reduction test with urine
        negativ result of specific test for glcose

39
Lack of aldolase B
 - hereditary fructose intolerance (fructose poisoning)
Very serious for newborns
Fructose-1-P accumulates in the liver cells to such an extent that most of the inorganic phosphate
is removed from the cytosol.
Phosphate is needed for function of glycogen phosphorylase, oxidative phosphorylation is inhibited
and hypoglycaemia also appears (Fru-1-P inhibits both glycolysis and gluconeogenesis).
Symptoms are vomiting, hypoglycemia, jaudice, hepatomegaly.
Symptoms can be seen after a baby starts eating food or formula.
Treatment: the intake of fructose and sucrose must be restricted.

40
Synthesis of fructose in polyol pathway
D-glucose
NADPH + H+
NADP+
D-glucitol
fructose (the main source of energy in sperm cells)
NAD+
NADH + H+
Aldose reductase
Liver, sperm, ovaries, seminal vesicles
Polyol dehydrogenase
Enzyme is absent in retina, kidneys, lens, nerve cells (see next page)
Many types of cells inc. liver, kidney, lens, retina

41
Polyol metabolism in diabetics
• If the blood concentration of glucose is very high (e.g. in diabetes mellitus), large amount of
glucose enter the cells
• The polyol pathway produces glucitol.
•It cannot pass efficiently through cytoplasmic membrane
it remains „trapped“inside the cells
•When sorbitol dehydrogenase is absent (lens, retina, kidney, nerve cells), sorbitol cannot be
converted to fructose and accumulates in the cell
•Some of the pathologic alterations of diabetes are attributed to this process (e.g. cataract
formation, peripheral neuropathy, retinopathy and other)

42
Metabolism of galactose
Galactose occurs as component of lactose in milk and in dairy products.
Hydrolysis of lactose in the gut yields glucose and galactose.
β-D-Galactopyranose

43
UDP-galactose (active form of galactose)
OH
OH
OH
It is formed in reaction with UDP-glucose

44
UDP-galactose
UDP-glucose
epimerase
reaction is reversible, can be used also for formation of glucose
Izomeration of glucose to galactose

45
Transformation of galactose into glucose in the liver
UDP-Glucose
UDP-Galactose
Glucose 1-phosphate
Gal-1-P uridyltransferase
UDP-Gal      4-epimerase
  UTP
PPi
Glc-1-P
Glc-6-P
Glucose
Glycolysis
Glycogen
UMP
H2O
Galactose is rapidly metabolized to glucose

46
Utilization of galactose
•Synthesis of lactose
•Synthesis of glycolipids, proteoglycans and glycoproteins

47
Galactosemia
•the hereditary deficiency of  Gal-1-P uridyltransferase
•Acummulation of galactose-1-P
•Interferention with metabolism of phosphates and glucose
•Conversion of galactose to galactitol in lens – kataracta
• Dangerous for newborns
•Non treated galactosemia leads to liver damage and retarded mental development
•Restriction of milk and milk-products in the diet

48
Biosynthesis of lactose
Unique for lactating mammary gland
UDP-galactose
glucose
Lactose (galactosyl-1,4-glucose)
Lactose synthase
Laktose synthase is a complex of two proteins:
• galactosyl transferase (present in many tissues)
• a-lactalbumin (present only in mammary gland during lactation, the synthesis is stimulated by
hormone prolactin)

49
Metabolismus of galactose in other cells
Galactose and N-acetylgalactosamine
are important constituents of
glycoproteins, proteoglycans, and glycolipids.
In the synthesis of those compounds in all types of cells, the galactosyl and N-acetylgalactosyl
groups are transferred from UDP-galactose and UDP-N-acetyl-galactose by the action of
UDP-galactosyltransferase.

50
The uronic acid pathway – synthesis and utilization of glucuronic acid
• An alternative oxidative pathway for glucose.
•It supplies glucuronic acid, and in most animals (not in humans, other primates, and guinea pigs)
ascorbic acid.

51
Biosynthesis and utilization of UDP-glucuronate
O
O
H
O
H
O
H
O
C
H
2
O
P
H
O
O
O
H
O
H
O
C
H
2
H
O
P
H
O
O
O
H
O
H
O
C
H
2
H
O
U
D
P
H
U
T
P
glucose-6-P
glucose-1-P
UDP-glucose
H
O
O
O
H
O
H
O
C
U
D
P
O
O
N
A
D
+
H
2
O
N
A
D
+
Glucuronides
(conjugation of xenobiotics)
UDP-glucuronate
Glycosaminoglycans
glucuronate

52
Examples of compound degraded and excreted as urinary glucuronides
Estrogen
Bilirubine
Progesterone
Meprobamate
Morphine

53
O
H
O
O
H
C
O
O
H
O
H
O
H
H
L-gulonate
L-xylulose
xylitol
D-xylulose
D-Xylulose-5-P
L-ascorbate
Primates, guinea-pigs etc.
It can enter pentose phosphate pathway
D-glucuronic acid
Degradation of D-glucuronic acid
block: →esential pentosuria
CO2

54
•Ascorbate is required for a range of essential metabolic reactions in all animals and plants. It
is  made internally by almost all organisms; the main exceptions are bats, guinea pigs, capybaras
and primates. Ascorbate is also not synthesized by some species of birds and fish. These animals
all lack the L-gulonolactone oxidase
•All species that do not synthesize ascorbate require it in the diet.
•Deficiency causes the disease scurvy in humans
•In human body it is necessary for the hydroxylation proline and lysine in the synthesis of
collagen, synthesis of carnitine, and synthesis of noradrenaline from dopamine.
Ascorbate

55
O
H
O
O
H
H
C
H
O
H
C
H
2
O
H
1
O
H
O
O
O
H
O
H
C
H
O
H
C
H
2
O
H
-2H
Synthesis of L-ascorbate
L-gulonate
1,4-lactone of L-gulonic acid
Ascorbic acid
C
O
O
C
C
C
C
C
H
H
O
O
H
H
H
O
H
H
O
O
H
H
H
H
-
+ H2O
L-gulonolactone
oxidase

56
A brief survey of major pathways in saccharide metabolism
GLUCOSE
Glc-6-P
Fru-6-P
Fru-1,6-bisP
Gra-3-P
GALACTOSE
Gal-1-P
Glc-1-P
GLYCOGEN
UDP-Glc
UDP-Gal
UDP-GlcUA
GlcUA
CO2
Xyl-5-P
CO2
FRUCTOSE
Glucitol
Fru-1-P
Glyceraldehyde
PYRUVATE
Oxaloacetate
Lactate
ACETYL-CoA

57
Hexosamine biosynthetic pathway - HBP
Glc-6-P
Glc-1-P
glycogen
Fru-6-P
glycolysis
Glc-N-6-P
1-3%
UDP-GlcNAc
Glycosylation (formation of glycoproteins, glycolipids, proteoglycans)

58
58
Functions of glycoproteins
Interaction between the cells, interaction with hormones, viruses
Antigenicity ( ABO groups etc.)
Components of extracelular matrix
Mucines (protective effect in digestion and urogenitary systém)

59
Saccharides found in glycoproteins and glycolipids
Abbreviation:
Hexoses:     Glucose Glc
    Galactose Gal
    Mannose Man
Acetyl hexosamines:   N-Acetylglucosamine GlcNAc
    N-Acetylgalactosamine GalNAc
Pentoses:     Xylose Xyl
    Arabinose Ara
Deoxyhexose
(Methyl pentose):     L-Fucose Fuc
Sialic acids:     N-Acetylneuraminic acid NeuNAc
                       (predominant)

60
Examples of saccharidic component of glycolipids or glycoproteins:
Ceramide (sphingolipid) or protein
Blood group substance A
NeuNAc
NeuNAc
Bi-antennary component of a plasma-type
(N-linked) oligosaccharide
The boxed area encloses
the pentasaccharide core
common to all N-linked
glycoproteins.

61
61
Glycosaminoglycans (mucopolysacharides)
• non branched heteropolysaccharides
• they are components of proteoglycans and peptidoglycans
• formed of repeated disaccharide units:
[ glycosamine – uronic acid]n
Present in intracelular matrix and cell surfaces (glycokalix)
They increase viscosity, support integrity of tissue
Examples: hyaluronate, dermatansulfate, heparansulfate, keratansulfate etc.

62
Synthesis of amino sugars
Fructose 6-phosphate
Glucosamine 6-phosphate
(2-Amino-2-deoxyglucosamine 6-phosphate)
CH–
CH=O
NH2
CH–OH
CH2–O– P
HO–CH
CH–OH
CH–OH
CH2–O– P
HO–CH
CH–OH
C=O
CH2–OH
Glutamic acid
Aminotransferase
Glutamine
The basic amino groups –NH2 of amino sugars are nearly always "neutralized“ by acetylation in the
reaction with acetyl-coenzyme A, so that they exist as N-acetylhexosamines.
Unlike amines, amides (acetamido groups) are nor basic.

63
CH3CO
C
H
2
C=O
COOH
HC–OH
HO–CH
HC–OH
CH2–OH
-NH–CH
HC–OH
Sialic acids
Sialic acids is the group name used for various acylated derivatives of neuraminic acid.
The most common sialic acid is N-acetylneuraminic acid:

64
N-Acetylmannosamine 6-phosphate
Phosphoenolpyruvate
N-Acetylneuraminic acid 9-phosphate
C
H
2
C=O
COO–
HC–OH
HO–CH
HC–OH
CH2–O–P
CH3CO
–NH–CH
HC–OH
HO–CH
HC–OH
CH2–O–P
CH3CO
–NH–CH
HC–OH
HC=O
CH2
COO–
C–O–P
Pi
+
Synthesis of sialic acid:

65
Glycosyl donors in glycoprotein synthesis
Glucose 6-P        Glucose 1-P                 UDP-Glucose            UDP-Galactose
                 UDP-Glucuronic acid         UDP-Xylose
Fructose 6-P        Mannose 6-P         Mannose 1-P                   GDP-Mannose
     GDP-L-Fucose
N-Acetylglucosamine 6-P       N-Acetylglucosamine 1-P                UDP-N-Acetylglucosamine
   UDP-N-Acetylmannosamine          UDP-N-Acetylgalactosamine
N-Acetylneuraminic acid                            CMP-N-Acetylneuraminic acid
CTP
UTP
GTP
  UTP

66
Mucopolysaccharidoses
•metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break
down glycosaminoglycans
•belong among lysosomal storage disease
•Enzymes necessary for breakdown of glycosaminoglycans are either not produced enough or do not
work properly.
•Over time, these glycosaminoglycans collect in the cells, blood and connective tissues. The result
is permanent, progressive cellular damage which affects appearance, physical abilities, organ and
system functioning, and, in most cases, mental development.
•7 types are known, they share many clinical features but have varying degrees of severity

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Disturbance in metabolism of glycoproteins - oligosaccharidoses
•Lysosomal storage disease
•
•Accumulation of oligosaccharides in lysosmes caused by lack of enzymes breaking down
oligosaccharides of glycoproteins
•Mannosidose, fucosidose, sialidose