Chapter 11- Carbohydrates Flashcards
Monosaccharides
The simplest units (monomers) of carbohydrates. The smallest ones are composed of 3 carbons. Monosaccharides are aldehydes or ketones with two or more hydroxyl groups. They have many isomers
Isomers
Have the same molecular formula but different structures. The main categories of isomers are constitutional isomers and stereoisomers
Constitutional isomers
Differ in the order of attachment of atoms
Stereoisomers
Have the same molecular formula but different structures. There are multiple different types.
Types of stereoisomers (2)
- Enantiomers
2. Diastereomers
Types of diastereomers (2)
- Epimers
2. Anomers
Enantiomers
Nonsuperimposable mirror images, you should be able to flip the molecules onto each other over a line drawn between them. An example is D-glyceraldehyde and L-glyceraldehyde. They are mirror images because their hydroxyl groups are attached on opposite sides.
Diastereomers
Isomers that are not mirror images. Example- D-altrose and D-glucose.
Epimers
Carbohydrates which vary in one position for the placement of the -OH group. The best examples are for D-glucose and D-galactose.
Anomers
Isomers that differ at a new asymmetric carbon atom formed on ring closure. Example: alpha-D-glucose and beta-D-glucose. The hydroxyl groups on the same carbon are pointing in different directions- one up, one down
Common monosaccharides (6)
- D-Ribose
- D-deoxyribose
- D-glucose
- D-mannose
- D-galactose
- D-fructose
Many common sugars exist in which form?
Cyclic
What is the chemical basis for the formation of cyclic sugars?
The reaction of an aldehyde or with an alcohol to form a hemiacetal, or the reaction of a ketone with an alcohol to form a
hemiketal.
Hemiacetal/hemiketal
A molecule that contains a central carbon bonded to an OH, an H, an R group, and an OR group. The difference between the 2 molecules is that they are use different reactants (aldehyde vs ketone). A cyclic hemiacetal results in another diastereomer form called an anomer
Which 2 cyclic sugar molecules are stable in solution?
- Pyranose rings
2. Furanose rings
How does the reaction to form a hemiacetal/hemiketal occur?
The hydroxyl group acts as a nucleophile during ring formation. Therefore, the oxygen becomes a member of the ring structure. The carbonyl carbon becomes chiral during this reaction, and is then known as the anomeric carbon.
Pyranose
A 6 carbon hemiacetal formed from an intramolecular reaction of glucose or from fructose when it’s free in solution. D-glucose can react to form either alpha-D-glucopyranose or beta-D-glucopyranose anomers
Furanose
A 5 carbon hemiketal formed from an intramolecular reaction of fructose
Alpha anomer
The hydroxyl at C-1 is below the plane of the ring
Beta anomer
The hydroxyl at C-1 is above the plane of the ring
Furanose anomers
The furanose form of fructose can also exist in anomeric forms in which the α and β forms refer to the orientation of the hydroxyl group located at carbon 2
Which cyclic forms does fructose assume?
Fructose forms both the pyranose form, which predominates when fructose is free in solution, and a furanose form, commonly seen in fructose derivatives (sweeteners)
Names of the ring structures of fructose (4)
- Alpha-D-fructofuranose
- Beta-D-fructofuranose
- Alpha-D-fructopyranose
- Beta-D-fructopyranose
How are D sugars identified?
All D sugars have the OH of their highest numbered chiral center on the right.
How are L sugars identified?
All L sugars have the OH of their highest numbered chiral center on the left
Which conformations can pyranose rings adopt?
Boat and chair. The boat form contains 5 carbons in the ring and literally looks like a paper boat
Orientations of carbon ring substituents in chair form (2)
Axial and equatorial
Why does beta D-glucopyranose adopt the chair conformation?
The axial positions are occupied by hydrogens, reducing steric hindrance
Envelope form
A conformation of furanose rings with four of the ring atoms in the same plane and one out of plane (the shape resembles an envelope with the flap open). The out-of-plane carbon is said to be in the endo position. There are C2 or C3 endo conformations. Ribose is one of the most important 5 membered rings in nature
Which two conformations are observed in the ribose component of most biomolecules?
- C-2 is out of the plane on the same side as C-5 (C-2-endo)
- C-3 is out of the plane on the same side as C-5 (C-3-endo)
These are considered envelope conformations
Which anomer of glucose predominates in solution?
A solution of glucose contains one-third α anomer, two-thirds β anomer, and about 1% open chain. The two anomeric forms are in equilibrium that passes through an open-chain form, and the free open-chain form reacts with oxidizing agents
Reducing sugars
Sugars that react with oxidizing agents, glucose is an example. However, any monosaccharide with a hemiacetal ring is considered a reducing sugar because aldoses can be oxidized.
Nonreducing sugars
Sugars that do not react with oxidizing agents
What happens when open chain glucose reacts with copper?
The copper is reduced, the glucose is oxidized
Oxidation
When an electron is removed from a molecule during a chemical reaction
Which molecules does glucose react with?
As a reducing sugar, glucose can react with amino groups, often Lys or Arg residues in proteins. Example: glucose can react with hemoglobin, forming glycosylated hemoglobin (hemoglobin A1c), which is fully functional. Determining the amount of hemoglobin A1c in the blood allows one to monitor the long-term control of blood glucose levels in diabetics
Advanced glycation end products
A modification where carbohydrates and proteins combine. This impairs protein function and has been implicated in a number of pathological conditions
O-glycosidic bond
A bond formed between an anomeric carbon atom and an oxygen atom of an alcohol (a monosaccharide is joined to an alcohol). Oligosaccharides containing two or more monosaccharides are linked by O-glycosidic bonds as well.
N-glycosidic bond
A bond formed between the anomeric carbon atom (of a monosaccharide) and an amine
Phosphorylation
A common modification of carbohydrates- phosphorylation makes the sugars anionic and prevents them from leaving the cell. It also facilitates the metabolism of sugars.
Common disaccharides (3)
- Sucrose
- Lactose
- Maltose
Sucrose
Sucrose is obtained from sugar cane and sugar beets and is composed of a glucose linked to a fructose. The linkage is α for glucose molecules and β for fructose molecules
Which molecule cleaves sucrose?
Sucrose is cleaved by sucrase (also called invertase)
Lactose
Lactose is the disaccharide of milk that consists of a galactose linked to a glucose by a β-1,4 linkage
Which molecule cleaves lactose?
Lactase
Maltose
Maltose is a degradation product of large oligosaccharides and is composed of two glucose molecules linked by an α-1,4 linkage
Which molecule hydrolyzes maltose?
Maltase
Storage forms of glucose (2)
- Starch
2. Glycogen
Glycogen
Glycogen is the glucose storage form in animals. Most glucose units in glycogen are linked by α-1,4-glycosidic bonds, with branches formed by α-1,6-glycosidic bonds about every 12 glucose units
Starch
In plants, glucose is stored as starch. There are 2 forms
2 forms of starch
- Amylose
2. Amylopectin
Amylose
Form of starch- a linear polymer of glucose units linked by α-1,4-glycosidic bonds
Amylopectin
Form of starch- a branched polymer, with an α-1,6-glycosidic bond for every 30 α-1,4-glycosidic bonds
Cellulose
A structural component of plants that is a homopolymer of glucose units linked by a β-1,4-glycosidic bond. The β linkage yields a straight chain capable of interacting with other cellulose molecules via H-bonds to form strong fibrils
Function of alpha linkages in starch and glycogen
The α linkages of starch and glycogen form compact hollow cylinders suitable for accessible storage
What factor determines polysaccharide structure?
Glycosidic bonds
Why is cellulose useful in the diet?
Although mammals cannot digest cellulose, it is still useful in the diet, increasing the rate at which digestion products pass through the large intestine
Why are soluble fibers useful in the diet?
Soluble fibers such as polygalacturonic acid (pectin) also aid in digestion, facilitating absorption of nutrients from the diet.
What is the function of oligosaccharides in human milk?
These carbohydrates are not digested by the infant, but play an important protective role against bacterial infection. Milk oligosaccharides appear to prevent the growth of certain Streptococcus bacteria, which can be transferred from the mother’s vaginal epithelium and cause pneumonia, blood poisoning, or meningitis in the infant. In milk, 150 oligosaccharides have been identified, but the composition and amount of these varies between individuals
3 main classes of glycoproteins
- Glycoproteins
- Proteoglycans
- Mucins or mucoproteins
Glycoproteins
Mainly protein by weight. Play a variety of roles, including as membrane proteins
Proteoglycans
Attached to a particular polysaccharide called a glycosaminoglycan. Mainly carbohydrate by weight. Play structural roles or act as lubricants, and are components of the extracellular matrix
Mucins or mucoproteins
Protein is characteristically attached to the carbohydrate by N-acetylgalactosamine. Mainly carbohydrate by weight. Often act as lubricants.
2 ways carbohydrates can be linked to proteins
- Attached to the nitrogen atom in the side chain of asparagine (N-linkage)
- Attached to the oxygen atom of the side chain of serine or threonine (O-linkage)
All N-linked polysaccharides have (2 components)
A common pentasaccharide core, consisting of three mannoses and two N-acetylglucosamine units. Additional monosaccharides may be attached to the core.
Erythropoietin
Erythropoietin is a glycoprotein that is 40% carbohydrate by weight. It is secreted into the blood by the kidneys to stimulate the production of red blood cells. Glycosylation of erythropoietin enhances the stability of the protein in the blood- there are multiple oligosaccharides attached to EPO.
GlcNAc
A protein modification, short for N-acetylglucosamine. GlcNAc is attached to serine or threonine (protein) residues by GlcNAc transferase. It is attached to proteins when nutrients are abundant. The attachment is reversible, with GlcNAcase removing the
carbohydrate. Improper regulation of the transferase has been linked to a number of pathological conditions
Glycosaminoglycans
Composed of repeating units of a disaccharide, one of which is a derivative of an amino sugar and one of which carries a negative charge as either a carboxylate or sulfate. Attached to proteoglycans.
Mucopolysaccharidoses
Pathological conditions that result from the inability to degrade proteoglycans. Example- Hurler disease (undigested sugars build up in the body, causing damage to the brain, heart, and other organs).
Cartilage composition
Cartilage is partially composed of the proteoglycan aggrecan as well as the protein collagen. The glycosaminoglycan component of aggrecan cushions joints by releasing water on impact and then
rebinding water.
Chitin
Chitin is a glycosaminoglycan found in the exoskeleton of insects, crustaceans, and arachnids. It is one of the most abundant carbohydrates in the world
Mucin glycosylation
The protein component of mucin is extensively glycosylated to serine and threonine residues, with the first carbohydrate being N-acetylgalactosamine. A region of the protein backbone rich in serines and threonines, called the variable number of tandem repeats (VNTR) region, is the site of glycosylation
Mucin functions and role in disease
Mucins serve as lubricants and adhere to epithelial cells, acting as a protective barrier. They are also overproduced in diseases such as bronchitis, cystic fibrosis, and in adenocarcinomas (cancers of the glandular cells of epithelial origin)
What is the purpose of processing chitin?
Chitosan can be used as a carrier to assist in drug delivery, as surgical stitches, as a component of personal care products, and as an additive in food products
What does the processing of chitin involve?
Processing of chitin (water-insoluble) to produce chitosan (water-soluble) involves its demineralization, treatment with proteases to
remove proteins. Then it is depigmented by dissolving the carotenoids and deacetylated
In general, where does protein glycosylation take place?
In the lumen of the endoplasmic reticulum and the Golgi complex
Where does N-linked glycosylation take place?
Begins in the endoplasmic reticulum and continues in the Golgi complex.
Where does O-linked glycosylation take place?
Only in the Golgi complex
Golgi complex function
The Golgi complex is a sorting center for proteins of various fates
Dolichol phosphate
An isoprene derivative that carries large oligosaccharides destined for attachment to asparagine
Glycosyltransferases
A large class of enzymes that catalyze the formation of glycosidic bonds
How are the monosaccharide substrates for glycosyltransferases activated?
By attachment to uridine diphosphate (UDP)
What determines blood groups?
Protein glycosylation patterns. All of the blood groups share the oligosaccharide foundation called O, with other groups (A and B) forming through different patterns. Individuals with the O blood type lack both enzymes, while individuals with the AB blood type express both enzymes. Individuals with either the A or B blood type express only one enzyme (the one capable of creating that oligosaccharide
Which glycosylation patterns determine A and B blood groups?
The A form is created if N-acetylgalactosamine is added to the O by a specific glycosyltransferase, while the B form is created if galactose is added by another transferase.
I-cell disease/ mucolipidosis 2
A disease where lysosomal enzymes are secreted into the blood rather than directed to the lysosome. In individuals with the I-cell disease, the mannose sugar of the enzymes is not phosphorylated within the Golgi, which incorrectly directs the hydrolytic enzymes outside the cell. Results in high concentration of hydrolytic enzymes in blood plasma, lysosomes are deficient so waste products build up and can’t be broken down.
How do lysosomal enzymes normally function?
Under normal conditions, phosphotransferase adds a phosphoryl group onto a mannose sugar found on the hydrolytic enzymes. This mannose 6-phosphate is used to direct the enzymes to the lysosomes. Mannose 6-phosphate acts as a marker bringing enzymes to lysosomes- enzymes don’t know they should go to the lysosomes
How can oligosaccharides be sequenced?
Oligosaccharides can be sequenced by using enzymes that cleave specific glycosidic bonds. MALDI-TOF is used to identify the released sugars
Glycan-binding proteins
These proteins bind to specific oligosaccharides on the cell surface. Lectins are a particular class of glycan-binding proteins.
Lectins function
The lectins on one cell recognize and bind to carbohydrates on another cell with multiple weak interactions. Such binding facilitates cell–cell interaction, which is important for processes such as building tissue and facilitating transmission of information.
Types of lectins (2)
- C-lectins
2. L-lectins
C-type lectins
In these molecules, a calcium ion facilitates interaction
between the protein and the carbohydrate
Selectins
Members of the C-type family. They bind immune-system cells to sites of injury in the inflammatory response. L-Selectin has another role- allowing attachment of an embryo to the mother’s uterus
L-lectins
Some are chaperones (assistants in protein folding) in the eukaryotic endoplasmic reticulum, while others act as strong insecticides
How do many pathogens gain entrance to cells?
Many pathogens gain entry into cells by first binding to carbohydrates on the cell surface. Example- influenza virus recognizes sialic acid residues linked to galactose residues that are present on cell-surface glycoproteins. The viral protein that binds to these sugars is a lectin called hemagglutinin
Which viral protein is responsible for the spread of infection?
Infection spreads when a viral protein, neuraminidase (sialidase),
cleaves the glycosidic bonds between the sialic acid residues and the rest of the cellular glycoprotein, freeing the virus to infect new cells. Some important anti-flu agents (e.g., Tamiflu, Relenza) are
neuraminidase inhibitors
Plasmodium falciparum
This is the parasitic protozoan that causes malaria, it also relies on glycan binding to infect and colonize its host.
What happens if glucose homeostasis is not maintained?
Hyperglycemia can lead to advanced glycation product and type 1 diabetes (absent insulin) or type 2 diabetes (ineffective insulin). One of several possibilities of a therapeutic target for these conditions is α-glucosidase (maltase)- medications currently exist to inhibit this enzyme
𝛂-Glucosidase (maltase) Inhibitors
Medications can help maintain blood glucose homeostasis
How do maltase inhibitors work?
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. 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
