Chapter 11- Carbohydrates Flashcards
(137 cards)
1
Q
Glycobiology
A
The study of the synthesis and structure of carbohydrates and how carbohydrates are attached to and recognized by other molecules, like proteins
2
Q
Glycomics
A
The study of the glycome- all of the carbohydrates and carbohydrate associated molecules that cells produce. It is dynamic and depends on cellular and environmental conditions
3
Q
Monosaccharides
A
Simple carbohydrates. They act as fuel for cells and are also fundamental to living systems. DNA is one example- it contains a sugar in its backbone. They are aldehydes or ketones that have two or more hydroxyl groups. The smallest monosaccharides contain 3 carbon atoms
4
Q
Monosaccharide chemical structure
A
They are aldehydes or ketones that have two or more hydroxyl groups
5
Q
Carbohydrates
A
Carbon based molecules that are rich in hydroxyl groups. The empirical formula for carbohydrates is (CH2O)n.
6
Q
Aldehyde
A
A carbon bonded to an R group and a hydrogen, and double bonded to an oxygen
7
Q
Ketone
A
A carbon bonded to 2 different R groups and double bonded to an oxygen
8
Q
Smallest monosaccharides (3)
A
- Dihydroxyacetone (a ketose)
- D- Glyceraldehyde (an aldose)
- L- Glyceraldehyde (an aldose)
All contain 3 carbons
9
Q
Ketose
A
A carbohydrate that contains a keto group (C=O)
10
Q
Aldose
A
A carbohydrate that contains an aldehyde group
11
Q
Simple monosaccharide naming
A
Simple monosaccharides that contain 3 carbon atoms are called trioses. Tetroses contain 4, pentoses contain 5, etc. Hexoses (6) include glucose and fructose, which are the most well known
12
Q
D-Glucose
A
Contains 6 carbons and is a simple monosaccharide (aldose). An essential energy source for virtually all forms of life
13
Q
D-Fructose
A
Contains 6 carbons and is a simple monosaccharide. It is a ketose instead of an aldose. Commonly used as a sweetener that is converted into glucose derivatives inside the cell. It is the most abundant ketohexose.
14
Q
Constitutional isomers
A
Compounds that have identical molecular formulas but differ in how the atoms are ordered
15
Q
Stereoisomers
A
Isomers that differ in spatial arrangement.
16
Q
Enantiomers
A
A type of stereoisomer where the molecules are mirror images of each other. D-glyceraldehyde and L-glyceraldehyde are examples.
17
Q
D and L isomers of monosaccharides
A
Most monosaccharides in vertebrates have the D configuration. D and L isomers are determined by the configuration of the asymmetric carbon atom farthest from the aldehyde or keto group. In the D configuration, OH is bonded to C-5 on the right and H is bonded on the left.
18
Q
Diastereoisomers
A
Isomers that are not mirror images of each other (the opposite of enantiomers).
19
Q
Number of possible stereoisomers
A
The number of possible stereoisomers equals 2^n, where n is the number of asymmetric carbon atoms
20
Q
D-ribose
A
The carbohydrate component of RNA. It is a 5 carbon aldose
21
Q
D-deoxyribose
A
The carbohydrate component of DNA. It is a 5 carbon aldose
22
Q
D-mannose
A
A 6 carbon monosaccharide (aldose). The configuration between D-mannose and D-glucose differs only at C2 (they are epimeric at this point)
23
Q
D-galactose
A
A 6 carbon aldose. D-glucose and D-galactose are epimeric at C4
24
Q
Epimers
A
Sugars that are diastereoisomers differing in configuration at only a single asymmetric center. D-glucose is epimeric with D-mannose and D-galactose at different carbons.
25
Common monosaccharides (6)
1. D-ribose
2. D-deoxyribose
3. D-glucose
4. D-mannose
5. D-galactose
6. D-fructose
26
Ketose vs aldose symmetry
Ketoses have one less asymmetric center than aldoses with the same number of carbon atoms
27
Predominant forms of many sugars in solution
In solution and in the cell, the open chain forms of sugars cyclize into rings. The ring form is their predominant form when in the cell
28
Hemiacetal
The product when an aldehyde reacts with an alcohol. This is the chemical basis for ring formation in sugars. In the hemiacetal molecule, the carbon is bonded to an OH and OR group in addition to the R and H the aldehyde was originally bonded to.
29
Pyranose
The resulting cyclic hemiacetal that occurs when glucose undergoes an intramolecular hemiacetal reaction. It is a 6 membered ring.
30
Hemiketal
A ketone reacts with alcohol to form a hemiketal- carbon is bonded to R, R prime, OH, and an OR double prime group
31
Hemiacetal formation
In glucose, this reaction occurs within the molecule. The C-1 aldehyde in the open chain form of glucose reacts with the C-5 hydroxyl group to form an intramolecular hemiacetal
32
Hemiketal formation
The C-2 keto group in the open chain form of a ketohexose (like fructose) can react with either the C-6 hydroxyl group to form a 6-membered cyclic hemiketal or the C-5 hydroxyl group to form a 5 membered cyclic hemiketal (furanose)
33
Furanose
The 5 membered ring formed when fructose undergoes a cyclic hemiketal reaction- the C-2 keto group reacts with the C-5 hydroxyl group
34
Anomers
Diastereomers that differ at a new asymmetric carbon atom formed on ring closure. This occurs during the formation of pyranose and furanose, and this is why both alpha and beta anomers are possible
35
Glucopyranose anomers
The C-1 of glucose becomes an asymmetric center- it's called the anomeric carbon atom. Alpha-D-glucopyranose and beta-D-glucopyranose are the 2 possible rings that can form. The alpha designation means that the OH group attached to C-1 is on the opposite site of the ring as C-6. Beta means that the OH group is on the same side of the ring as C-6.
36
Which anomer of glucopyranose is most prevalent?
An equilibrium mixture of glucose contains around one third alpha anomer, two thirds beta anomer, and less than 1% is the open chain form
37
Fructofuranose anomers
The C-2 of fructose is the anomeric carbon atom. Fructose forms both pyranose and furanose rings, so there are 4 possible products. The alpha forms have the C-2 OH group below C-1 (below the plane of the ring), the beta forms have the C-2 OH group above C-1
38
Beta-D-fructopyranose function
Found in honey and is one of the sweetest chemicals known. Heating converts beta-fructopyranose into beta-fructofuranose, reducing its sweetness. Therefore, corn syrup with a high concentration of fructose in the beta-D-pyranose form is used as a sweetener in cold drinks rather than hot ones.
39
Where do the pyranose and furanose forms of fructose predominate?
The pyranose form predominates in fructose that is free in solution. The furanose form predominates in many fructose derivatives, like sweeteners
40
Conformations of pyranose rings (2)
Chair and boat conformations
41
Chair conformation of pyranose rings
Pyranose rings are not planar. The substituents on the ring carbon atom can have an axial or equatorial orientations. Axial bonds are almost perpendicular to the plane of the ring, while equatorial bonds are parallel to the plane. Axial substituents sterically hinder each other if they are located on the same side of the ring. Equatorial substituents are less crowded
42
Why is the boat form of glucose disfavored?
It is sterically hindered. The chair form is more stable because hydrogen atoms occupy all of the axial positions and cause less steric hindrance
43
Envelope form
The arrangement of furanose rings, which are also not planar. They are puckered so 4 atoms are nearly coplanar and the 5th is located away from the plane. In ribose, either C-2 or C-3 is out of the plane on the same side as C-5. They are called C-2 endo and C-3 endo respectively.
44
Reducing sugars
Glucose is considered a reducing sugar because it can nonspecifically react with a free amino group (like lysine or arginine) to form a stable covalent bond. Reducing sugars are sugars that react with oxidizing agents
45
Hemoglobin A1c
Glucose reacts with hemoglobin to form glycosylated hemoglobin (hemoglobin A1c). This is a reduction reaction. Monitoring changes in the amount of glycosylated hemoglobin is used to monitor diabetes. Glycosylated hemoglobin remains in circulation, so the amount of modified hemoglobin corresponds to the long term regulation of glucose levels. In nondiabetic individuals, less than 6% of hemoglobin is glycosylated, but uncontrolled diabetics have 10% of hemoglobin glycosylated
46
Are reducing reactions with glucose harmful?
The glycosylation of hemoglobin does not affect oxygen binding, so it's benign. However, reducing reactions with other proteins, like collagen, can be detrimental because the glycosylations alter the normal biochemical function of the modified proteins
47
Advanced glycation end products
Reactions between proteins and carbohydrates can sometimes impair protein function. Glycosylations can alter the normal function of the modified proteins. After the primary modification, cross linking can occur between the site of the first modification and elsewhere in the protein, further compromising function. These modifications are called AGEs, and they have been implicated in aging, arteriosclerosis, and diabetes
48
N-glycosidic bond
A bond formed between the anomeric carbon atom of a carbohydrate and the nitrogen atom of an amine. This occurs when nitrogenous bases are attached to ribose units to form nucleosides
48
Glucose reducing reaction with copper
Glucose reacts with cupric ion (Cu 2+) and reduces it to cuprous ion (Cu+). Glucose is oxidized to gluconic acid
48
O-glycosidic bond
A bond formed between the anomeric carbon atom of a carbohydrate and the oxygen atom of an alcohol. These bonds are prominent when carbohydrates are linked together to form long polymers, and when they are attached to proteins
49
How can carbohydrates be modified through reactions with other molecules?
1. O-glycosidic bonds
2. N-glycosidic bonds
3. The attachment of functional groups to carbons other than the anomeric carbon
50
Phosphorylation of sugars
Addition of phosphoryl groups is a common modification of sugars- when glucose is broken down, it is converted into glucose 6-phosphate. Phosphorylation makes sugars anionic. It also creates reactive intermediates that will more readily undergo metabolism. This is why intermediates in metabolic pathways are typically phosphorylated.
51
What is the purpose of making sugars anionic through phosphorylation?
The negative charge prevents the sugars from spontaneously leaving the cell through crossing the lipid membrane. It also prevents them from interacting with transporters of unmodified sugar
52
Oligosaccharides
Built by the linkage of two or more monosaccharides through O-glycosidic bonds. Maltose is a disaccharide where two D-glucose residues are bonded by a glycosidic bond between the alpha anomeric form of C-1 on one sugar and the hydroxyl oxygen atom on C-4 of the adjacent sugar. This is called an alpha-1,4-glycosidic bond.
53
Oligosaccharide directionality
The reducing end of the oligosaccharide is the carbohydrate unit that contains the anomeric carbon atom that has reducing activity since it can form the open chain form. It's considered the reducing end even when it's bound to another molecule (like a protein) and no longer has reducing properties
54
Disaccharide
Consists of 2 sugars joined by an O-glycosidic bond. Examples are sucrose, lactose, and maltose
55
Sucrose
Common table sugar- obtained from sugar cane or sugar beets. It is a disaccharide that joins the anomeric carbon atoms of a glucose unit and a fructose unit. The configuration of this glycosidic linkage is alpha for glucose and beta for fructose
56
Invertase (sucrase)
Cleaves sucrose into its component monosaccharides
57
Lactose
The disaccharide of milk. Consists of galactose joined to glucose by a beta-1,4-glycosidic linkage.
58
Lactase
The human enzyme that hydrolyzes lactose to monosaccharides. Bacteria uses beta-galactosidase.
59
Maltose
Comes from the hydrolysis of large polymeric oligosaccharides like starch and glycogen. Linked by alpha-1,4 linkages
60
Maltase (alpha-glucosidase)
Hydrolyzes maltose into glucose. It also degrades oligosaccharides linked by alpha-1,4-glycosidic linkages
61
Where are sucrase, lactase, and maltase located?
On the outer surfaces of epithelial cells lining the small intestine.
62
Why can't free glucose molecules be stored?
In high concentrations, glucose will disturb the osmotic balance of the cell. This can result in cell death. Therefore, glucose is stored in a large polymer, which is not osmotically active
63
Polysaccharides
Large polymeric oligosaccharides that are formed by the linkage of multiple monosaccharides. They are important for energy storage and for maintaining the structural integrity of an organism
64
Homopolymer
A polysaccharide where all of the monosaccharide units are the same. Glycogen is the most common one in animals
65
Glycogen
A homopolymer- it is the storage form of glucose in animals. Glycogen is present in most of our tissues but is most abundant in the muscles and liver. It is a large, branched polymer, and most of the glucose units in glycogen are linked by alpha-1,4-glycosidic bonds. The branches are formed by alpha-1,6- glycosidic bonds, which are present about once every 12 units and make glycogen highly branched
66
Starch
A homopolymer that is the storage form of glucose in plants. It is found in wheat, potatoes, and rice. There are 2 forms- amylose and amylopectin
67
Amylose
The unbranched type of starch, consists of glucose residues in alpha-1,4 linkages
68
Amylopectin
The branched form of starch. It has 1 alpha-1,6 linkage per 30 alpha-1,4 linkages
69
Alpha-amylase
An enzyme secreted by the salivary glands and the pancreas. It hydrolyzes amylopectin, amylose, and glycogen.
70
Cellulose
The other major polysaccharide of glucose in plants. It serves a structural role as it is part of the plant cell wall, contrary to starch which serves a nutritional role. It is an unbranched polymer of glucose residues joined by beta-1,4 linkages- this contributes to its difference in properties from starch and glycogen. The beta configuration allows cellulose to form very long, straight chains
71
Fibrils of cellulose
Formed by parallel chains that interact with one another through hydrogen bonds. It creates a rigid, supportive structure. The chains themselves are formed by beta linkages between the glucose residues and have high tensile strength
72
How do alpha linkages contribute to the properties of glycogen and starch?
They produce a hollow helix that is well suited to the formation of a more compact, accessible store of sugar
73
Importance of cellulose and other plant fibers to the diet
Soluble fiber, like pectin, slows the movement of food through the gastrointestinal tract. It allows for improved digestion and the absorption of nutrients. Insoluble fiber, like cellulose, increases the rate at which digestion products pass through the large intestine. This increase in rate can minimize exposure to toxins in the diet. Mammals cannot digest cellulose because they lack the necessary enzymes to break it down
74
Oligosaccharides in human milk
More than 150 different oligosaccharides have been identified in human milk, and the amount and composition vary among women. Infants can't digest them, but they play a large role in protecting against bacterial infection. These oligosaccharides are not present in formula
75
Which bacterial infection can oligosaccharides protect infants from?
Certain types of streptococcus bacteria colonize the vaginal epithelium of 20% of healthy women. Transmission to the infant can cause pneumonia, septicemia, and meningitis. Milk oligosaccharides appear to prevent the growth of the bacteria. They may serve as a fuel source for beneficial bacteria in the infant. They may also prevent the attachment of microbial pathogens to the intestinal wall of the newborn
76
Glycoprotein
A carbohydrate group that is covalently attached to a protein. These modifications are common- 50% of the proteome consists of glycoproteins. There are 3 classes
77
3 classes of glycoproteins
1. Glycoproteins
2. Proteoglycans
3. Mucins (mucoproteins)
78
Glycoproteins (the class)
The protein constituent in this class is the largest component by weight. Glycoproteins play multiple roles. They are components of cell membranes and are responsible for cell adhesion and sperm binding to eggs. Other glycoproteins are formed by linking carbohydrates to soluble proteins
79
Glycosylated proteins
A glycoprotein where a carbohydrate is linked to a soluble proteins, modifying the protein. Many of the proteins secreted from cells are glycosylated, including most proteins present in the serum component of blood. Glycosylation increases the complexity of the proteome.
80
Proteoglycans
The second class of glycoproteins. The protein component of proteoglycans is conjugated to a glycosaminoglycan. Carbohydrates make up a larger percentage by weight (95%) of the proteoglycan, so it more closely resembles a polysaccharide.
81
Glycosaminoglycan
A type of polysaccharide, bound to proteins to form proteoglycans. Many glycosaminoglycans are made of repeating units of disaccharides containing a derivative of an amino sugar (either glucosamine or galactosamine). At least one of the two sugars in the repeating unit has a negatively charged carboxylate or sulfate group.
82
Mucins (mucoproteins)
The third class of glycoproteins. The protein component is extensively glycosylated at serine or threonine residues by N-acetylgalactosamine. Predominantly made of carbohydrates. N-acetylgalactosamine is the carbohydrate that is typically bound to the protein- it is an amino sugar, because an amino group replaces a hydroxyl group. Mucins are a key component of mucus and serve as lubricants
83
Glycoforms
Different glycosylated forms of a given protein. These proteins have several potential glycosylation sites
84
N-linkage
Sugars in glycoproteins that are attached to the amide nitrogen atom in the side chain of asparagine. All N-linked oligosaccharides have a pentasaccharide core in common- it consists of 3 mannose and 2 N-acetylglucosamine residues. Additional sugars can be attached to this core to form the variety of oligosaccharide patterns found in glycoproteins
85
O-linkage
Sugars in glycoproteins that are attached to the oxygen atom in the side chain of serine or threonine.
86
An asparagine residue can accept an oligosaccharide only if
The residue is part of Asn-X-Ser or an Asn-X-Thr sequence. X can be any residue except for proline. Which potential sites are glycosylated depends on aspects of the protein structure and on the cell type in which the protein is expressed
87
Erythropoietin (EPO)
A glycoprotein hormone that is secreted by the kidneys and stimulates the production of red blood cells. It is N-glycosylated at 3 asparagine residues and O-glycosylated on a serine residue. Mature EPO is 40% carbohydrate by weight. Glycosylation enhances the stability of the protein in the blood.
88
Why is unglycosylated EPO less stable?
Unglycosylated proteins are rapidly removed from the blood by the kidneys
89
Uses of EPO
Recombinant human EPO is used to treat anemias. However, some endurance athletes have used recombinant EPO to increase their RBCs and therefore their oxygen carrying capacity. Some forms of prohibited human EPO can be distinguished from natural EPO by detecting differences in their glycosylation patterns through the use of isoelectric focusing
90
G1cNAc glycosylation reaction
N-acetylglucosamine attaches to serine or threonine residues of cytoplasmic, nuclear, and mitochondrial proteins. This is a post-translational glycosylation reaction that modifies the protein. It is catalyzed by O-GlcNAc transferase
91
G1cNAc concentration
Reflects the active metabolism of carbohydrates, amino acids and fats- its attachment to the protein indicates that nutrients are abundant. The attachment is reversible, with GlcNAcase removing the carbohydrate. GlcNAcylation sites are also potential phosphorylation sites, so O-G1cNAc transferase and protein kinases may be involved in cross talk to modulate one another's signaling activity. Dysregulation of G1cNAc transferase has been linked to insulin resistance, diabetes, cancer, and neurological pathologies
92
Proteoglycan functions (3)
1. Structural components and lubricants in connective tissue.
2. Mediate the adhesion of cells to the extracellular matrix
3. Bind factors that regulate cell proliferation
93
The properties of proteoglycans are determined primarily by
The glycosaminoglycan component.
94
Major glycosaminoglycans in animals (5)
1. Chondroitin sulfate
2. Keratan sulfate
3. Heparin
4. Dermatan sulfate
5. Hyaluronate
95
Heparin
A glycosaminoglycan- acts as an anticoagulant to assist the termination of blood clotting
96
Mucopolysaccharidoses
A collection of diseases that result from the inability to degrade glycosaminoglycans. Hurler disease is an example. Clinical features vary with the disease, but all mucopolysaccharidosis result in skeletal deformities and reduced life expectancies
97
Hurler disease
A mucopolysaccharidosis where glycosaminoglycans can't be degraded. The excess of these molecules are stored in the soft tissue of the facial regions, which causes the characteristic facial features. Symptoms include wide nostrils, a depressed nasal bridge, thick lips and earlobes, and irregular teeth.
98
Extracellular matrix of cartilage
Proteoglycans are found in the ECM of cartilage- aggrecan (a proteoglycan) and collagen are key components of cartilage. Collagen provides structure and tensile strength, while aggrecan serves as a shock absorber. Water is bound to glycosaminoglycans found in proteoglycans, attracted by the many negative charges. Aggrecan can cushion compressive forces because the absorbed water enables it to spring back after being deformed. Osteoarthritis results when water is lost from proteoglycan with aging
99
Aggrecan structure
It is a large molecule made of 2397 amino acids. The protein has 3 globular domains, and the site of glycosaminoglycan attachment is the extended region between globular domains 2 and 3. Many molecules of aggrecan are noncovalently bound through the first globular domain to a very long filament formed by linking together molecules of the glycosaminoglycan hyaluronate.
100
Chitin
A glycosaminoglycan found in the exoskeleton of insects, crustaceans, and arachnids. It is the second most abundant polysaccharide in nature
101
Functions of mucins
Mucin form large polymeric structures and are found in mucus secretions. They are synthesized by specialized cells in the tracheobronchial, gastrointestinal, and genitourinary tracts. Mucins are also abundant in saliva, where they function as lubricants. They adhere to epithelial cells and act as a protective barrier (from stomach acid, inhaled chemicals, and bacterial infections). They also hydrate the underlying cells. Additionally, mucins have roles in fertilization, the immune response, and cell adhesion
102
Mucin structure
Mucins contain a region of the protein backbone called the variable number of tandem repeats (VNTR) region, which is rich in serine and threonine residues that are O-glycosylated. The carbohydrate component accounts for 80% of the molecule by weight. Domains rich in cysteine facilitate the polymerization of the molecule. A number of core carbohydrate structures are connected to the protein component of mucin.
103
VNTR
Region of the mucin protein backbone that is the site of glycosylation. It forces the molecule into an extended conformation. It is rich in serine and threonine residues that are O-glycosylated
104
Role of mucins in disease
Mucins are overexpressed in bronchitis and cystic fibrosis, and the overexpression of mucins in characteristic of adenocarcinomas- cancers of the glandular cells of epithelial origin.
105
Where does protein glycosylation take place?
Glycosylation takes place inside the lumen of the endoplasmic reticulum and in the Golgi complex-organelles that play central roles in protein trafficking. The protein is synthesized by ribosomes attached to the cytoplasmic face of the ER membrane, and the peptide chain is inserted into the lumen of the ER. The N-linked glycosylation begins in the ER and continues in the Golgi complex, but the O-linked glycosylation takes place only in the Golgi complex
106
Dolichol phosphate
A specialized lipid molecule located in the ER membrane and containing about 20 isoprene (C5) units. A large oligosaccharide destined for attachment to the asparagine residue of a protein is assembled on this molecule. The terminal phosphate group of the dolichol phosphate is the site of attachment of the oligosaccharide. The oligosaccharide is now considered activated (energy rich), and the activated form is transferred to a specific asparagine residue of the growing polypeptide chain by an enzyme located on the lumenal side of the ER
107
Role of the Golgi apparatus in glycosylation of proteins
Proteins from the ER are transported to the Golgi complex (a stack of flattened membranous sacs). Carbohydrate units of glycoproteins are altered and elaborated in the Golgi complex. O-linked sugar units are formed in the Golgi complex. N-linked sugars arrive from the ER as a component of a glycoprotein and are modified in different ways. The Golgi complex is the major sorting center of the cell. Proceeds leave from the Golgi complex and go to lysosomes, secretory granules, or the plasma membrane, according to their amino acid sequences and 3D structures
108
Golgi complex as a sorting center
The Golgi complex is the sorting center in the targeting of proteins to lysosomes, secretory vesicles, and the plasma membrane. The cis face of the Golgi complex receives vesicles from the endoplasmic reticulum. The trans face send a different set of vesicles to target sites. Vesicles also transfer proteins from one compartment of the Golgi complex to another
109
Glycosyltransferases
Catalyze the formation of glycosidic bonds. They synthesize complex carbohydrates
110
Donors and acceptors for glycosyltransferases
The most common carbohydrate donors are activated sugar nucleotides (like UDP-glucose). The attachment of a nucleotide enhances the energy content of the molecule. The acceptor substrates vary and include carbohydrates, serine, threonine, and asparagine residues of proteins, lipids, and even nucleic acids
111
Reaction mechanism of a glycosyltransferase reaction
The sugar to be added comes from a sugar nucleotide (UDP-glucose). The sugar forms a bond with the OH group at the end of UDP. The acceptor on the sugar molecule leaves, as does the hydrogen in the OH group
112
Blood groups are designated by
Different glycosylation patterns due to the presence of one of the 3 different carbohydrates (A, B, and O) attached to glycoproteins and glycolipids on the surface of red blood cells. These structures have an oligosaccharide foundation (the O antigen) in common.
113
How are A and B blood group antigens different from the O antigen?
They differ from the O antigen by the addition of one extra monosaccharide. This is either N-acetylgalactosamine (for A) or galactose (for B) through an alpha-1,3 linkage to a galactose component of the O antigen. Specific glycosyltransferases add the extra monosaccharide to the O antigen.
114
Heritability of blood types
Each person inherits the gene for one glycosyltransferase of this type from each parent. The type A transferase specifically adds N-acetylgalactosamine, while the type B transferase adds galactose. In the AB blood group, both enzymes are present. The O phenotype results if both enzymes are absent
115
Importance of blood types
If a person is given a blood transfusion and an antigen not normally present in a person is introduced, the immune system recognizes it as foreign. Red blood cell lysis occurs, causing hypotension, shock, kidney failure, and death from circulatory collapse. Blood types exist because there is selective on humans to vary blood type to give various advantages. If a parasite contains an antigen that is normally present in the blood, it might not be recognized as foreign. Only people with certain blood types would be protected
116
Errors in glycosylation can cause
Disease- certain types of muscular dystrophy can be linked to improper glycosylation of dystroglycan (a membrane protein that linked the ECM with the cytoskeleton)
117
I-cell disease (mucolipidosis 2)
A lysosomal storage disease. The lysosomes are organelles that degrade and recycle damaged cellular components or material brought into the cell by endocytosis. In I-cell disease, lysosomes contain large inclusions of undigested glycosaminoglycans and glycolipids. The inclusions are present because the enzymes normally responsible for the degradation of the glycosaminoglycans are missing from affected lysosomes. The active enzymes are synthesized but, due to the absence of appropriate glycosylation, they are exported to the blood and urine instead of being delivered to the lysosomes. The enzymes normally contain a mannose 6-phosphate residue that directs them to the correct location
118
Mannose 6-phosphate residue
The enzymes responsible for the degradation of glycosaminoglycans contain a mannose 6-phosphate residues as a component of an N-oligosaccharide. It serves as the marker directing the enzymes from the Golgi complex (site of synthesis) to the lysosomes. In I-cell disease, the attached mannose lacks a phosphate. These patients are deficient in the N-acetylglucosamine phosphotransferase catalyzing the first step in the addition of the phosphoryl group. This causes 8 essential enzymes to be delivered incorrectly
119
I-cell disease symptoms
Severe psychomotor retardation and skeletal deformities (similar to those in Hurler disease)
120
Formation of a mannose 6-phosphate marker
A glycoprotein destined for delivery to lysosomes acquires a phosphate marker in the Golgi compartment. G1cNAc phosphotransferase adds a phospho-N-acetylglucosamine unit to the 6-OH group of a mannose. Then, an N-acetylglucosaminidase removes the added sugar to generate a mannose 6-phosphate residue in the core oligosaccharide
121
Glycan-binding proteins
Proteins that bind specific carbohydrate structures on neighboring cell surfaces. These proteins are found in all living organisms. Lectins are one class of glycan binding proteins
122
Lectins
A class of glycan-binding proteins. They facilitate cell-cell contract by interacting with carbohydrates on other cells. The mannose 6-phosphate receptor is a lectin which binds the enzymes in the Golgi apparatus and directs them to the lysosome. Lectins can be divided into classes on the basis of their amino acid sequences and biochemical properties
123
How do lectins facilitate cell-cell contact?
A lectin usually contains 2 or more carbohydrate binding sites. The lectins on the surface of one cell interact with combinations of carbohydrates displayed on the surface of another cell. Lectins and carbohydrates are linked by weak noncovalent interactions. These interactions ensure specificity but allow unlinking as needed. They are similar to Velcro- each interaction is weak, but combined, they're strong. They are important for processes such as building tissue and facilitating transmission of information.
124
C type lectins
A large class of lectins found in animals. They have a homologous domain of 120 amino acids that is responsible for carbohydrate binding. A calcium ion on the protein acts as a bridge between the protein and the sugar through direct interactions with sugar OH groups. The carbohydrate binding specificity of a particular lectin is determined by the amino acid residues that bind the carbohydrate. C- type lectin functions- receptor mediate endocytosis and cell-cell recognitions
125
Selectins
Members of the C-type lectins family. They bind immune system cells to sites of injury in the inflammatory response.
126
L-selectin
Involved in the immune system, binds specifically to carbohydrates on lymph node vessels. It is produced by embryos when they are ready to attach to the endometrium of the mother's uterus. The endometrial cells present an oligosaccharide on the cell surface. When the embryo attaches through lectins, the attachment activates signal pathways in the endometrium to make implantation of the embryo possible
127
L-lectins
Found mainly in leguminous plants and can act as insecticides. Other types of L-lectins (calnexin and calreticulin) are prominent chaperones in the eukaryotic endoplasmic reticulum
128
Chaperones
Proteins that facilitate the folding of other proteins
129
Role of cell-surface carbohydrates in disease
Many pathogens gain entry into specific host cells by adhering to cell surface carbohydrates. The influenza virus recognizes sialic acid residues linked to galactose residues that are present on cell surface glycoproteins. A lectin called hemagglutinin is a viral protein that binds to these sugars
130
Influenza virus proteins
A viral protein called hemagglutinin is a lectin that binds to carbohydrates on the cell surface. After binding hemagglutinin, the virus is engulfed by the cell and begins to replicate. Viral assembly results in the budding of the viral particle from the cell. Once assembly is completed, the viral particle is still attached to sialic acid residues of the cell membrane by hemagglutinin on the surface of the new virions. A viral protein called neuraminidase cleaves the glycosidic bonds between the sialic acid residues and the rest of the cellular glycoprotein, which frees the virus to infect new cells and spread through the respiratory tract. Drugs like Tamiflu and Relenza are inhibitors of this enzyme
131
Viral hemagglutinin's carbohydrate binding specificity may play a role in
Species specificity of infection and ease of transmission. Avian influenza is one example- it is typically lethal and spreads readily from bird to bird. Humans can be infected by the virus, but it's rare, and human to human transmission is very rare. This is because the avian virus hemagglutinin recognizes a different carbohydrate sequence from that recognized in human influenza. Humans have the sequence to which the avian virus binds, but it is located deep in the lungs. Therefore, it is not easily transmitted
132
Plasmodium falciparum
The parasitic protozoan that causes malaria. It also relies on glycan binding to infect and colonize its host. Glycan-binding parasitic proteins injected by the mosquito bind to the glycosaminoglycan heparin sulfate on the liver- this initiates the parasite's entry into cell. When it exits from the liver, it invades RBCs by using another glycan-binding protein to bind to the carbohydrate component of glycophorin (an RBC membrane glycoprotein).
133
𝛂-Glucosidase (Maltase) Inhibitors importance
May be able to be used to maintain blood glucose homeostasis. Maintaining glucose homeostasis is essential- hyperglycemia can lead to advanced glycation products and type 1 or type 2 diabetes. α-glucosidase medications are a type of pharmacologic intervention to inhibit the enzyme and help the body to maintain homeostasis. The first step in digestion of glycogen and starch is degradation into smaller oligosaccharides by α-amylase (secreted by the salivary glands and pancreas). These are then further digested by α-glucosidase.
134
Examples of maltase inhibitors (2)
Two competitive inhibitors of this enzyme are acarbose and miglitol; either can be administered at the start of a meal to reduce post-meal glucose absorption in type 2 diabetes
135
