Carbohydrate metabolism Schegg Flashcards
1
Q
What are complex polysaccharides?
A
any oligosaccharide with more than one type of sugar residue
2
Q
What are these:
- Glycosaminoglycans (GAGs)
- Proteoglycans
- glycosylate lipids
- GPI anchors
- Glycoproteins
A
complex polysaccharides
3
Q
What do complex polysaccharides vary in?
A
ratio of carb to protein to lipid
nature of carb
4
Q
The formation of complex polysaccharides are dependent on two important classes of enzymes, what are they?
A
glycosyltransferases and glycosidases
5
Q
What do glycosyltransferases do?
A
transfer a saccharide from a donor
6
Q
What are the donors of glycosyltransferases?
A
UDP
GDP
CMP
Dolichol
7
Q
What are the acceptors of glycosyltransferases?
A
protein (-OH or -NH2)
lipid
non-reducing end of another sugar
8
Q
sumarize the reaction of glycosyltransferase
A
donor-glycose+ acceptor->glycose-acceptor + donor
9
Q
What are glycosyltransferases very specific for?
A
sugar transferred
acceptor
the site
anomeric linkage formed (alpha or beta)
10
Q
How many classes of gglycosyltransferases are there in eukaryotic cells and what are they?
A
7 mannosyltransferase galactosyltransferase glucosyltransferase fucosyltransferase N-acetylgalactosamine transferase N-acetylglucosamine transferase N-acetylneuraminyl transferase (sialyltransferase)
11
Q
To use the glycosyltransferase mannosyltransferase what sugar do you need and what donors can you use?
A
mannose
GDP-Man
Dolichol-Man
12
Q
To use the glycosyltransferase galactosyltransferase what sugar do you need and what donors can you use?
A
galactose
UDP-Gal
13
Q
To use the glycosyltransferase glucosyltransferase what sugar do you need and what donors can you use?
A
Glucose
UDP-Glc
Dolichol-Glc
14
Q
To use the glycosyltransferase fucosyltransferase what sugar do you need and what donors can you use?
A
frucose
GDP-fuc
15
Q
To use the glycosyltransferase N-acetylgalactosamine transferase what sugar do you need and what donors can you use?
A
N-acetylgalactosamine
UDP-GalNAc
16
Q
To use the glycosyltransferase N-acetylglucosamine transferase what sugar do you need and what donors can you use?
A
N-acetylglucosamine
UDP-GlcNAc
17
Q
To use the glycosyltransferase N-acetylneuraminyl transferase (sialyltransferase) what sugar do you need and what donors can you use?
A
N-acetylneuraminic (sialic acid)
CMP-NANA (CMP-SA)
18
Q
What do glycosidases do?
A
remove specific sugar residues ad is very specific for the bond hydrolyzed
19
Q
There are more than (Blank) glycosidic bonds in mammalian oligosaccharides
A
40
20
Q
What is this:
Proteins which contain one or more saccharides bound covalently to protein
A
glycoproteins
21
Q
(blank) of all eukaryotic proteins are glycosylated.
A
1/2
22
Q
glycoproteins are all synthesized on the (blank) via the secretory pathways
A
RER
23
Q
The (blank) membrane is highly glycosylated
A
erythrocyte
24
Q
How much carbohydrate is in a glycoprotein?
A
it is variable
25
How much IgG is in a glycoprotein?
4% by weight
26
What do carb portions look like on glycoproteins?
usually less than 15 residues, branched, can have heterogeneity in any portion
27
Whereare carbs located on glycophorin A (a glycoprotein)?
all carbs is in amino terminal half of the protein
28
What is the importance of glycoproteins in cell membrane?
Important in:
Behavior of cells
Biological function of membrane
Receptor activation, Signal transduction,
Endocytosis, Cell adhesion, Leukocyte trafficking
Cell surface glycans are the first molecules encountered by:
other cells, antibodies, viruses, bacteria (the glycoprotein can be on the virus, e.g., HIV)
29
What is this about:
Important in:
Behavior of cells
Biological function of membrane
Receptor activation, Signal transduction,
Endocytosis, Cell adhesion, Leukocyte trafficking
Cell surface glycans are the first molecules encountered by:
other cells, antibodies, viruses, bacteria (the glycoprotein can be on the virus, e.g., HIV)
importance of glycoproteins in cell membrane
30
Why are glycoproteins important in mucus?
lubricates and protects tissue in respiratory, GI and female reproductive systems
31
What are made up of glycoproteins and secreted to stimulate specific cells or tissues into action.
hormones such as FSH, LH, CG
32
What plasma proteins are made up of glycoproteins?
Immunoglobulins, orosomucoids, ceruloplasmin, plasminogen, prothrombin
33
What are the 2 basic types of glycoproteins?
N linked glycoproteins and O linked glycoproteins
34
How does an N-linked glycoprotein work?
first sugar residue is is GlcNAc (glucose bound to N-acetyl) and it is N-linked to ASN-X-Thr/Ser
X cannot be Pro and is rarely Asp, Glu, Leu or Trp
35
All N-linked glycoprotein carbohydrate portions are assembled initially the same way, but are then processed to give a great deal of variability. What are the three N-linked glycoprotein final structures?
High-mannose, hybrid, complex
36
What are some example of N-linked oligosaccharides?
hyprid type-> IgM
High mannose type-> chicken ovalbumin, sindbis virus
COmplex type-> IgG
37
How do you synthesize N-linked glycoproteins via Dolichol phosphate?
Dolichol phosphate on the cytoplasmic side of the ER accepts GlcNAc->
glycosylation occurs->
Structure is flipped across the ER membrane into lumen of ER->
four more Man's and 3 Glu's are added->
It is transferred to Asn on a protein being synthesized.
(Synthesis begins by adding to the cytoplasmic side of dolichol. After stepwise glycosylation's it is flipped into the ER lumen and transferred from dolichol to proteins being synthesized )
38
Once you syntheisze N-linked glycoproteins via dolichol phosphate, what are the two different pathways it can take?
1) add some phosphates in cis golgi and then can go to lysosomes
2) can go throughout golgi via vesicles getting rid of sugars and adding other sugars and make an array of diverse products than can be secreted or go to membrane
39
the sugars that can be added or taken away to N-linked glycoproteins can be done via what 2 enzymes?
glycosidases and glycosyl transferases
40
Explain how to make an O-linked glycoprotein
A protein is synthesized and folded and moves to golig. The protein must have a Ser or Thr to be able to accept the first sugar which is GalNAc, after GalNAc, sugars can be added until we run out of glycosyltransferases
41
What are the products formed for an O-linked glycoprotein?
variable, depends on number and type of glycosyltransferases in a cell
42
When does oligosaccharide synthesis stop?
when there is no transferase with the right specificity available (produces heterogeneity)
43
In (blank), saccharides are also O-linked to 5-OH Lys.
collagen
44
How do you make an N-linked glycoprotein?
start with a protein with the amino acid Asn to accept a GlcNAc. Then you add sugars and become either high mannose glycoprotein, a hybrid glycoprotein, or a complex glycoprotein.
45
(blank) are O-linked highly glycosylated glycoproteins that are secreted or membrane-bound. They can form gels that lubricate, provide chemical barriers and hold water. In the central part of the protein, up to ½ of the amino acids are serine or threonine. These are heavily glycosylated.The oligosaccharide chains are often sulfated and contain sialic acid.
Mucins
46
(blank) can form gels that lubricate and provide barriers and hold water.
mucins
47
In the central of mucin, up to 1/2 of the amino acids are (lank) and (blank). These are heavily glycosylated.
Serine and threonine
48
The oligosaccharide chains of mucin are often (blank) and contain (blank)
sulfated and contains sialic acid
49
(blank) are increased in many cancers, asthma, bronchitis, COPD, and cystic fibrosis.
Mucins
50
Many O-linked oligosaccharides contain (blank) or (blank)
sialic acid
| acetylneuraminic acid
51
DIsorders of glycoprotein synthesis and degredation are called (blank).
congential disorders of glycosylation (CDGs)
52
What are disorders of N-linked glycosylation?
```
Type 1 (most common)
and Type 2
```
53
What is a Type 1 N-linked glycosylation disorder?
Involve early steps in the synthesis of N-linked glycoproteins
54
What are these:
CDG –Ik deficit in mannosyltransferase I (adds first mannose); results in death in 1-10 months
CDG-Ia most common; deficit in phosphomannosemutase II (forms mannose-1-phosphate, the precursor of UDP-mannose)
N-linked glycosylation disorders
55
What are type II N-linked glycosylation disorders?
Enzymatic defects in N-glycan processing enzymes
56
What is the most common congenital disorder of glycosylation?
CDG-1a (defect in phosphomannomutase II)
57
What is this:
enzymatic defects in O-mannosylation and O-fucosylation
- example: Walker-Warburg syndrome
deficit in O-mannosyltransferase I
causes α-dystroglycanopathies (congenital muscular dystrophy)
Disorders of O-linked glycosylation
58
What is this:
| CMP-sialic acid transporter deficiency
Combined N- and O- glycosylation defects
59
What are some characteristics of Congential disorders of glycosylation?
```
rare,
autosomal recessive
- Symptoms
psychomotor retardation
malfunction of organ systems, especially nervous system, muscles and intestines in infants
```
60
Glycoproteins are catabolized by (blank) and (blank)
lysosomal exoglycosidases and endoglycosidases.
61
```
What are these caused by and what are they called:
aspartylglucosylaminuria
beta-manosidosis
alpha-mannosidosis
GM2 Gangliosidosis variant O (sandhoff)
GM1 gangliosodosis
Mucolipidosos
frucosidosis
```
defects in lysosomal glycosidase activities
| lysosomal storage diseases
62
Incompletely degraded compounds accumulate in (blank) and (blank)
tissues and urine
63
What is the deficient enzyme in Mucolipidosis (sialidosis)
sialidase
64
What can lysosomal storage diseases cause?
skeletal abnormalities, hepatosplenomegaly, cataracts, and mental retardation
65
What does GlcNAc-P glycosyltransferase do?
it is an enzyme that marks lysosomal proteins for their destination
66
What is I cell disease or mucolipidosis II?
deficient GlcNAc-P glycosyltransferase
67
Where do you find GlcNAc P glycosyltransferase?
Proteins are secreted from the cell and are found in plasma and other body fluids.
68
(blank) are seen in fibroblasts (I cells)
dense inclusion bodies
69
If you have I cell disease, what symptoms will you have?
severe psychomotor retardation, many skeletal abnormalities, coarse facial features, restricted joint movement and death by age 8
70
Some glycoproteins are anchored to the extracellular side of plasma membranes via (balnK)
Glycosylphosphatidylinositol (GPI)
71
Explain the structure of GPI and how it can be modified.
contains a core tetrasaccharide structure plus additional saccharides.
Can be modified by extra sugar residues
72
(blank) anchors and binds proteins and concentrates them in lipid rafts.
GPI
73
Explain the synthesis of GPI
1. Begins on cytoplasmic side of ER
2. N-Acetyl-glucosamine is added to phosphatidylinositol using UDP-GlcNAc. The molecule is transferred to luminal side.
3. 3 mannose sugars are added as dolichol-P-mannose
4. Ethanolamine is attached.
5. Attachment of protein:
a. An amino group of GPI phosphoethanolamine attacks a specific amino acyl group near the protein’s C-terminus
b. a 20- to 30- amino acid C-terminal signal peptide is released
c. proteins end up on exterior of plasma membrane
74
(blank) is an isoprenoid embedded into the ER membrane. The common core from all N-linked glycoproteins are assembled on this as a lipid linked polysaccharide.
dolichol
75
How do we synthesize glycolipids?
vi glycosyltransferase (this little guy synthesizes almost everything)
76
The majority of glycolipids are (blank)
sphingolipids
77
What is the structure of a sphingolipid?
it is a sphingosine connected o fatty acid plus an H, a monosoaccharide or a complex oligosaccharide structure
78
If a sphingosine is attached to a fatty acid and an H, what is this structure called?
a ceramide
79
If a sphingosine is attached to a fatty acid and a single mnosaccharide what is the lipid called?
cerebrosides
80
If sphingosine is attached to a fatty acid and complex oligosaccharide structures, what is this called?
globosides and gangliosides
81
What are the four major class of sphingolipids?
cerebrosides, sulfatides, globosides, ganglioides.
82
(blank) account for 15% of lipids in white matter
| uses PAPS reaction on galactocerebroside
sulfatides
83
Globosides and gangliosides are synthesized by a series of specific (blank) and are made from a glucocerebroside(cerebrosides) :)
glycosyltransferases
84
How do we make a globoside or ganglioside?
we start with a cerbroside (glucocerebroside) and utilize glycosyltransferase to add remaining hexoses
85
Disorders of Glycolipid Degradation often mainly affect (blank) system
nervous
86
(blank) are degraded by lysosomal enzymes (many are the same enzymes that degrade glycoproteins)
Sphingolipids
87
Deficiency in (blank) result in sphingolipid storage disease, a type of lysosomal storage disease.
lysosomal glycosidases
88
(blank) diseases can cause an acculumation of glycolipid and gangliosides.
sphingolipid storage disease (lysosomal storage disease)
89
What kind of disease Tay Sachs?
sphingolipid storage disease (lysosomal storage disease)
90
```
What is the kind of disease are these:
GM1 gangliosidosis?
Sandhoff?
sialidosis?
Fabry?
Gaucher?
Krabbe?
Metachromatic Leukodystrophy?
```
sphingolipid storage disease (lysosomal storage disease)
91
What causes niemann-pick disease?
deficiency in sphingomyelinase
92
If you have problems breaking down GM1, globoside, and sphngomyelin, to ceramide then you may develop what symptons?
mental retardation, motor deterioration
93
In tay-sachs, a buildup of (blank) in galgion cells will appear as a milky halo around the fovea of the eye. In addition you will find deposits of these in the lysosomes.
Gangliosides
94
The A, B and O antigens on the surface of red blood cells are (blank)
complex polysaccharides
95
What is this:
-erythrocyte surface sphingolipids
- glycoproteins, particularly on band 3 protein, an anion exchange protein of the RBC membrane (composes 25% of the membrane weight)
They are also found in plasma membranes of many tissues and secreted into various fluids.
A, B, and H (O) antigens
96
What happens on all blood types and adds fucose to galactose to make a core H antigen?
fucosyltransferase (coded by H gene) turns fucose to galactose in an alpha 1/2 linkage
97
The (blank) antigen is the acceptor for a glycosyltransferase coded for by the ABO gene (on chromosome 9). There are several allelic forms of this gene.
H
98
The (blank) allele for the ABO gene codes for N-acetylgalactosamine glycosyltransferase. The GalNAc is added to the terminal Gal in an α 1,3 linkage.
A
99
The (blank) allele for the ABO gene codes for galactosyltransferase. The Gal is added to the terminal Gal in an α 1,3 linkage.
B
100
The (blank) allele for an inactive protein. Therefore, the (blank) groups has neither GalNAc or Gal at terminus of the antigen.
O
101
The H gene in epithelial and secretory tissues that produces the H antigen is called (blanK) . Not all tissues have this, if they dont, then they utilize (blank).
FUT2
| FUT3
102
(blank) which encodes an fucosyltransferase with loose specificity:
- can create a α-1/3 or α-1/4 glycosidic bond to GlcNAc
- can act on either:
1) the H antigen (producing Leb or Ley antigen)
2) the precursor to the H antigen (producing the Lea or Lex antigen).
FUT3
103
No FUT2, + FUT3 –>?
| +FUT2, +FUT3 - >?
Lea or LeX
| Leb or Ley
104
(blank) are glycoproteins or sphingolipids, not synthesized by RBCs.
Lewis Antigens
105
Lewis antigens are glycoproteins or sphingolipids, not synthesized by RBCs.
These are produced in epithelial and secretory tissues, but are detected in blood. Why?
The glycosylated sphingolipids circulate in plasma and absorb to the surface of RBCs. They cannot be glycosylated further.
106
The Leb glycan may act as a receptor for (blank).
Heliobacter pylori
107
(blank) are absent in patients suffering from the leukocyte adhesion deficiency syndromes, LADI and LADII (caused by a mutation in the GDP-fucose transporter).
Lewis antigens
108
The (blank) antigen is elevated in many cancers.
Ley
109
Describe GAGs
```
Long and unbranched
composed of disaccharide repeating units
have sulfate groups
highly charged
specific recognition sites for proteins
```
110
In GAGS, what are the disaccharide repeating units containing?
- a hexosamine (GlcNAc ,GalNAc, glucosamine)
| - a uronic acid (usually D-glucuronic acid or L-iduronic acid)
111
GAGs often have sulfate groups linked by.....
ester bonds and amide bonds to amino groups of glucosamine
112
(blank) is not sulfated in GAGs
hyaluronate
113
What makes GAGs highly charged?
urinates and sulfates
(form extended rod-like helices in solution
- negatively charged carboxylate groups occur on opposite sides of the helix)
114
What about GAGs provide for specific recognition by a variety of protein ligands that bind electrostatically to the GAGs?
Charge patterns
115
GAGs may be attached to extracellular protein to form (blank)
proteoglycans
116
Where do we find GAGs?
ground substance and extracellular space
117
What is this:
- comprise connective tissue such as cartilage, tendon, skin and blood vessel walls
- also contain collagen and elastin fibers
extracellular space
118
(blank) are not easily compressed, highly viscous and elastic ( good for lubricating joints), have negative charge to attract sodium and potassium ions which allow for water absorptions, and maintain fluids and electrolytes w/in tissues.
GAGs
119
What is this:
1.Disaccharide repeating unit:
D-glucuronic acid + GlcNac – hooked by β(→3) bond. The disaccharides units are linked β(1→4)
2. Not sulfated
3. Occupies large volume in solution
Produces clear, highly viscous solution. Exhibits a non-Newtonian viscosity
4. Acts as lubricant and shock absorber in ground substance in:
-extracellular matrix of cartilage and tendons
-synovial fluid
-vitreous humor of vertebrate eye (gives eye its jellylike consistency)
-umbilical cord
-capsules surrounding certain pathogenic bacteria
5. Binds K+, Na+, and Ca2+ tightly
hyaluronate
120
```
What are these:
chondroitin sulfate
dermatan sulfate
heparin
heparan sulfate
keratan sulfate
Hyaluronate
```
GAGs
121
(blank) is used as an anti-coagulant used for patients , e.g., post surgery, to reduce clotting
heparin
122
(blank) binds to the enzyme inhibitor antithrombin III (AT) causing a conformational change that results in AT activation. The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin.
heparin
123
Persons with heterozygous antithrombin III deficiency are (blank) to heparin.
resistant
124
How do we make GAGs?
glycosyltransferases= sugar +protein orsugar →
| sulfation via PAPS synthetase
125
Some GAGs are assembled on the protein backbone, this is best understood via (blank)
chondroitin sulfate
126
What is this:
Defects in sulfate transporter into the cell: diastophic dysplasia (DTD), atelostegebesis type II (AOII),
achrodrogenesis type IB (ACG-1B)
PAPS synthetase: spondyloepimetaphyseal dysplasia (Pakistani type)
All are characterized by short stature, short or bowed limbs
Sulfation Defect Diseases
127
What is this:
- large molecules with a central protein core and extensions of glycosaminoglycans
- some have > 1 type of GAG (e.g., aggrecan, syndecan, betaglycan)
- principle component of the ground substance
- negatively charged, attract sodium and potassium ions.
- size and relative amounts of proteoglycans change with:
development
age
disease
proteoglycans
128
What are the major extracellular species of proteoglycans?
aggrecan and versican
129
(blank) has a bottle brush structure. There are a ton of these attached non covalently to a hyaluronic acid and is stabilized by link proteins. Each one of these further has a bunch of chondroitin sulfate and keraton bound to it.
Aggrecan
130
Aggrecan can bind many different sugars in three different regions, what are they?
inner region->sugars bind to an Asn
central region-> GAGs bind via Ser/Thr (many are keratan sulfate)
outer region-> has chondroitin sulfate chains linked via Gal-Gal-Xyl-O-Ser/Thr
131
Do all aggrecan and other proteoglycans bind to hyaluronic acids?
no
132
What are these:
Syndecan, CD44, Thrombomodulin, Glypican
proteoglycans that are integral membrane proteins or membrane anchored proteins
133
What are these:
| Neorocan, Brevican, Cerebrocan, Phosphacan
Proteoglycans that occur in the nervous system
134
What are the proteoglycans that interact with hyaluronic acid?
aggrecan
versican
neurocan
135
What are the proteoglycans of the Basal lamina?
Perleean
agrin
bamacan
136
What are the small leucine-rich proteoglycans?
decorin
fibromodulin
osteoglycin
137
Proteoglycans are degraded through sequential actions of lysosomal enzymes: (blank X4)
Deacetylases
Sulfatases
Proteases
Glycosidases
138
Deficiencies in these Deacetylases, Sulfatases, Proteases, Glycosidases,cause a variety of (blank).
Mucopolysaccharidoses
139
Name that disease:
| skeletal abnormalities and physical retardation
hurler and hunter
140
Name that disease:
| mild physical defects and severe retardation
Sanfilippo
141
Name that disease:
| decreased activity of all known sulfatases
Multiple Sulfatase deficiency (MSD)
142
What enzymes effect the regulation of proteoglycan metabolism?
hexosamine synthesis
F6P glutamine transminase
UDP-glucose dehydrogenase
143
Proteoglycan and glycoprotein synthesis is controlled at the level of (blank)
hexosamine synthesis
144
What is the main regulatory step of proteoglycan metabolism? Is this subject to feedback inhibition?
```
F6P glutamine transaminase
Feedback inhibition (via the NAcs)
```
145
What is another regulatory step of proteoglycan metabolism?
UDP glcose dehydrogenase (inhibited by UDP-xylose)
146
(blank) is the first sugar added to the protein core in chondroitin sulfate, heparin, heparin sulfate and dermatan sulfate. If core protein decreases, UDP-xylose increases and inhibits dehydrogenase.
UDP-xylose
147
(blank) is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. n-acetylneuraminic acid, NANA) linked on the sugar chain.
i.e. a complex lipid in gray matter
This function in cell recognition
Ganglioside
148
What kind of diseases are these:
| hurler, hunter, sanflippo, multiple sulfatase deficiency
Mucopolysaccharidoses
149
Tay-Sachs disease is a lysosomal storage disease in which (blank) are not degraded.
gangliosides
