Lecture 2: Carbohydrates Flashcards
What are the most abundant organic molecules in nature?
Carbohydrates
What are some roles of Carbohydrates?
Are a significant source of dietary calories (fuels, energy stores, metabolic intermediates); form part of structural framework of DNA and RNA; form structural components of cell walls in bacteria and plants (are the principle constituents of the fibrous materials of plants); are linked to many proteins and lipids where they act as mediators of molecular recognition events particularly at the cell surface.
What does it mean for a carbohydrate to be “polyhydroxyl”?
Contain several hydroxyl groups
What two functional groups do CHO contain? Describe their structure.
Aldehyles or Ketones. Aldehydes are a carbon double bonded to an oxygen, and single bonded to a hydrogen and one substituent. Ketones are also double bonded to an oxygen but single bonded to two substituents (R groups)
Which structures are used in Fischer projections and what do horizontal and vertical lines mean?
Only linear CHO are drawn in Fischer and horizontal lines mean the bonds are coming towards you; vertical lines means the bonds are going away from you
What is an asymmetric carbon?
Also called a chiral carbon, an asymmetric carbon is linked to four different types of atoms or groups.
What are monosaccharides called when they have 3, 4, 5, or 6 carbons attached?
triose, tetrose, pentose, hexose
What are monosaccharides? How are they classified?
Simple sugars. Classified based on number of carbon atoms they contain or whether they contain an aldehyde or ketose.
What is a CHO with a ketone or an aldehyde called?
ketose; aldose
What is a stereoisomer?
isomers that have identical chemical connectivity but have different spacial arrangement of their atoms
What is an enantiomer?
It is a stereoisomer that has a mirror image. Have the some physical and chemical properties but not the same biological properties since biological macromolecules are mostly all chiral
What is a disastereomer?
Stereoisomers that are not mirror images of one another. Generally do not have identical physical and chemical properties.
If a CHO has 4 asymmetric carbons, how many possible stereoisomers can it have?
- 2^4 = 16
What are isomers that differ at only one position called?
Epimers
How do you locate the anomeric carbon in a ring structure of CHO?
It is always next to the bound oxygen
The absolute configuration of CHO is measured where?
At the asymmetric carbon furthest away from the aldehyde or ketone (hydroxyl group is on the right side of Fischer drawing)
Are most sugars in the D- configuration or L-?
D
What happens to aldehydes and ketones during cyclization?
Aldehydes and ketones are attacked by hydroxyl groups (alcohols, water) to yield hemiacetals or hemiketals. This process is reversible. If the hydroxyl group comes from the same molecule, it is called a intramolecular hemiacetal/hemiketal.
Which carbons react with each other in glucose to form rings? Fructose?
The C-1 aldehyde in open chain glucose reacts with the C-5 hydroxyl group to form a six membered pyranose ring; the C-2 keto group in the open chain fructose reacts with the C-5 hydroxyl group to form a five membered furanose ring. An additional (new) asymmetric center is formed at the anomeric carbon atom (C-1 in aldoses and C-2 in ketoses) in these cyclizations
What two possible isomers result from hemiacetal formation?
alpha and beta anomers
The equilibrium conversion of the two anomers is known as ________
mutarotation
In solution, the alpha and beta anomers exist in _______. When glucose is in this state, how much of each anomer exists?
Equilibrium; 2/3 beta, 1/3 alpha, 1% open chain. Not all sugars are in the 2:1 ratio. The ratio will depend on the specifics of the individual sugar structures
6 membered rings formed by CHO such as glucose are referred to as ________. Why?
Pyranosides, or pyranose sugars because they resemble pyran.
5 membered rings are referred to as ______. Why?
Furanosides, or furanose sugars because they resemble furan.
Cyclic forms of sugars are sometimes drawn in the simplified ________ projections
Haworth
Are cyclic sugar molecules planar?
No. Haworth projects are simplified views of the molecule but do not reflect the physical details of the CHO structure
D-ribose and 2-deoxy-D-ribose tend to form ______ cyclic structures.
Furanosides (5 sided rings)
What are examples of groups that can be used to modify monosaccharides
amino groups, carboxylic acids, acetylations, sulfations, phosphorylations
How can monosaccharides be activated during metabolism? What are some examples?
Addition of phosphate or nucleotide. Glucose-6-phosphate; UDP-glucose
How can aldoses function as reducing agents?
Aldehydes can be readily oxidized to carboxylic acids
Sugars with aldehyde groups are referred as _______ and in polymers of sugars, the end containing the free aldehyde is known as the _________ of the polymer.
reducing sugars; reducing end
Can cyclic sugars be considered reducing sugars?
Yes. Even if the vast majority of a sugar is found in a cyclic form (hemiacetal, not an aldehyde), it is still considered a reducing sugar if the cyclic form is in equilibrium with a linear aldose form
Which cyclic sugars are known as non-reducing sugars? What is one example?
Sugars that are not in equilibrium with a form containing a free aldehyde group. One example is methyl glucopyranoside. The methyl group locks it the hemiacetal form
Why is the reducing character of a sugar important?
The reducing character of an aldehyde can be used in diagnostic tests (Benedict’s reaction to test for glucose in the urine of diabetics)
True or false: Sugar aldehydes can also be reduced to the corresponding alcohol.
True. Glucose –> Sorbitol
The _______ bond links monosaccharides into larger structures
glycosidic bond
How is an O-glycosidic bond formed?
When the anomeric carbon of a sugar is attached to a hydroxyl group on another molecule
The glycosidic bond is a _______ reaction and proceeds with the loss of _______.
Condensation; water
Lactose is a _______ containing an O-glycosidic bond between _____ and ______.
Disaccharide; anomeric carbon of galactose & hydroxyl group on glucose
How is an N-glycosidic bond formed?
Anomeric carbon is bound to an amine group H2N- (eg. UDP-glucose)
True/False: Sugars participating in glycosidic bonds undergo mutarotation
False: the glycosidic bond is stable and these sugars do not undergo mutarotation
oxidation of an aldehyde yields a _____; reduction of an aldehylde yields a ______
carboxylic acid; alcohol
Are hemiacetals redox active?
No, bc no aldehyde
What is a methyl group?
-CH3 (alkyl derived from methane)
What is glycogen?
A large, branched homopolymer of glucose
What kind of bonds and branches are found in glycogen?
alpha-1,4 glycosidic bonds and alpha 1,6 branches
What are polysaccharides?
Glycosidic bonds linking many monosaccharides
What is cellulose and how does it differ from glycogen?
Another polymer of glucose but the bonds are beta-1,4 instead of alpha-1,4
What is Amylose and how does it differ from glycogen?
One type of Starch. Another polymer of glucose but only has alpha-1,4 bonds. Does not have alpha-1,6 branches
What are some uses for sugar polymers?
energy storage (glycogen, amylose); structural building blocks (cellulose)
How branching possible when forming glycogen from glucose?
Large number of hydroxyl groups on the molecule that are available for glycoside bond formation
What is amylopectin? What type of bonds does it have?
Another type of starch (nutritional reservoir for plants). Has alpha-1,4 and alpha-1,6 glycosidic bonds like glycogen but has a lower degree of branching
What are two types of polysaccharides used by plants as a nutritional reservoir?
Amylose and Amylopectin
What is one of the most abundant organic molecules in the biosphere?
Cellulose
What is the principle storage form of glucose in animal cells?
Glycogen
What are glycosaminoglycans (GAGS)? What are some examples?
sugar heteropolymers that are highly negatively charged hydrated gels/lubricants (eg. Chondroitin sulfate to cushion joints; Hyaluronic acid, keratan sulfate, heparin). They are made up of repeating disaccharide motifs.
What are glucoconjugates?
Sugars attached to other types of molecules such as proteins or lipids
What are glycoproteins and what are the two types?
Proteins linked to oligosaccharides; N-linked or O-linked glycosidic bonds
What are proteoglycans?
GAGs (glycosaminoglycans) attached to protein molecules
What are some functions of proteoglycans in the extracellular matrix?
provides strength; cushions and lubricates joints; participates in cell-to-cell signaling; regulates morphogenesis and cell migration during development; is degraded an resynthesized during tissue remodeling and wound healing.
________ are major components of the strong mesh-like coats the surround and protect bacteria
proteoglycans
How is the injection of bacterial coat components alone sufficient to elicit strong immune responses in humans and other animals? What bacterial coat component is frequently used for this purpose?
CHO are present in most bacterial coats - the antigens that animals’ immune systems use to recognize bacteria typically contain CHO. LPS (lipopolysaccharide)
N-linked glycosylation in glycoproteins occurs on the side chains of _______ residues
asparagine (Asn)
Whether or not a given Asn is glycosylated depends on what factors?
The cellular location of the protein, the sequence context of the Asn residue (Asn-X-Ser or Asn-X-Thr), and the protein structure (availability to glycosyl transferases)
True/False: cytoplasmic or nuclear proteins are N-glycosylated?
False. N-glycosylation occurs within the endoplasmic reticulum so only proteins that reside in or pass through this compartment carry this modification.
Only proteins with N-linked sugars are found in:
The ER or golgi, targeted to membranes or secreted.
N-linked carbohydrates are added to proteins in the ER and then edited in the ________
Golgi complex
What is a dolichol pyrophosphate?
A specialized lipid in the ER membrane in which a core oligosaccharide (destined for attachment to asparagine residues) anchors to.
The core oligosaccharide consists largely of ______ sugars. What happens to this molecule in the ER?
mannose; It is preassembled, attached to a dilochol pyrophosphate and then transferred to a nascent protein.
What happens the protein/CHO complex when it goes from the ER to the golgi?
As the protein progresses through the golgi apparatus en route to secretion from the cell, the core oligosaccharide can be trimmed and additional CHO added. The enzymes that mediate this editing process are found at different points along the secretory pathway.
What do CHO structures do for proteins in a glycoprotein complex?
They can assist in protein folding, help control protein targeting, affect the lifetime of secreted proteins and when displayed on cell-surface proteins, can control cell-cell recognition.
How can you tell how far a molecule has progressed along the secretory pathway (ER –> golgi)
By assessing how much the original core oligosaccharide has been altered (enzymes that mediate editing process are found at different points along the secretory pathway)
During assembly of an N-linked oligosaccharide, the first stage of synthesis takes place in the _______
cytoplasm on the exposed pyrophosphate of a membrane embedded dolichol molecule.
Synthesis of the precursor is completed in the lumen of the ER after ______ of the dolichol pyrophosphate and attached oligosaccharide.
flipping
What drug blocks the first step in the assembly of oligosaccharide precursor (The addition of N-acetyl glucosamine to dolichol pyrophosphate)
Tunicamycin
True/false: the basic machinery for glycosylation has been greatly altered throughout evolution
False; it has been conserved across all kingdoms of life
Where is a key target for antimicrobial agents?
Peptidoglycan biosynthesis
What enzymes are responsible for the addition of CHO to proteins and for editing of these CHO structures.
Glycosyltransferases
What enzymes break glycosylic bonds or edit them?
glycosidases
What contributes to microheterogeneity in CHO structures associated with glycoproteins?
Different enzymes compete with each other for the addition or removal of a monosaccharide at a given site. i.e. different copies of a given protein contain different oligosaccharide structures
Microheterogeneity in CHO is sometimes referred to as the ______
Sugar code
What are the roles of N-linked glycosylation of proteins?
Aid in protein folding; increase stability of folded protein; participate in specific recognition events, immune system evasion; targeting of proteins to different cellular compartments
What is glycomics?
The study of the various CHO structures associated with proteins and lipids as well as their functions (unraveling the sugar code)
O-linked glycosylation: involves the addition of sugars to the side chains of ____ or ____ residues (or occassionally ______)
serine, threonine; tyrosine
How many types of O-linked glycosylation are there?
two; one that occurs in the Golgi for transport outside the cell (secreted & membrane bound), and one that targets nuclear and cytoplasmic proteins (intracellular)
What is the difference between O-linked and N-linked glycosylation specifically related to the Golgi?
In O-linked, Glycosylation occurs in a step-wise process similar to and simpler than for N-linked. Because O-linked happens in the golgi, it occurs well after the protein has been synthesized whereas N-linked occurs during translation or immediately afterwards in the ER
What are mucins?
protein components of mucus; a large O-linked CHO structure
What are examples of large O-linked CHO structures?
Mucins and proteoglycans
What are proteoglycans?
Heavily glycosylated molecules that are a major component of the extracellular matrix (glucosaminoglycans + proteins)
Describe O-linked glycosylation that occurs in the cytoplasm?
It involves a reversible addition of only a single monosaccharide N-acetylglucosamine (GlcNAc)
What is the possible significant of O-linked GlcNAc?
Important regulatory phenomena affecting signal transduction cascades, transcription, translation, and the cell cycle. O-GlcNAc can compete with phosphorylation at specific AA residues.
Attachement of GlcNAc to _____ or _____ is the only kind of protein glycosylation found in the cytoplasm or nucleus of eukaryotes.
Serine, threonine
What are lectins?
Proteins that recognize specific mono- or oligosaccharides
Mammalian lectins are frequently found where?
at the cell surface
What molecules are responsible for reading the sugar code?
lectins. These proteins facilitate cell-cell contacts and are very specific in terms of CHO structures they recognize.
What is the role of lectins?
facilitate cell-cell contacts. The also allow cells to selectively take up certain glycosylated proteins, help the organism distinguish self from non-self; employed by pathogens to target CHO structures on host cells.
What is a lipopolysaccharide (LPS)?
a bacterial glycolipid conjugate that the mammalian cells recognize as non-self and triggers an immune response
What is a ganglioside?
A glycolipid that is highly abundant in the brain
Where are glycolipids frequently displayed?
on the cell surface
What is a glycosylphosphatidylinositol (GPI) anchor? How is this accomplished?
Serves to anchor many different proteins to the cell membrane. This is accomplished by linking the protein to a pre-assembled sugar-lipid structure in the lumen of the ER shortly after the protein is synthesized.
GPI anchored proteins are thought to associated with cholesterol-rich patches that form within membranes, known as ______
lipid rafts
Are GPI anchores distributed evenly over the cell surface or clustered in discrete bunches?
clustered together in the lipid rafts
glycosaminoglycans and proteoglycans are important components of:
ECM in mammals and protective coats surrounding microbes
What type of O-linked glycosylation may compete with phosphorylation?
Intracellular O-GlcNAc
Is mucin formed in the golgi or the cytoplasm?
golgi
Delivering leukocytes from circulation to sites of inflammation is an example of _____ function in biology
lectin
What are homopolymers of glucose?
amylose, cellulose, glycogen
Glucose reacts slowly with hemoglobin and other proteins to form covalent compounds. Why is glucose reactive? What is the nature of the product formed?
glucose is reactive because of the presence of an aldehyde group in its open-chain form. The aldehyde group slowly condenses with amino groups to form an amino ketone.
N-acetylgalactosamine is a key component of this glycoprotein
mucoprotein
A glycoprotein containing glycosaminoglycan
proteoglycan
Glucose and fructose are reducing sugars. Sucrose (table sugar) is a disaccharide consisting of both fructose and glucose. Is sucrose a reducing sugar? Explain.
No, sucrose is not a reducing sugar. The anomeric carbon atoms of glucose and fructose can act as the reducing agent, but in sucrose, the two anomeric carbon atoms are joined by a covalent bond and thus not available to react
Compare the number of reducing ends to nonreducing ends in a molecule of glycogen. At which end (reducing or nonreducing) would you expect most metabolism to take place?
Each glycogen molecule has one reducing end whereas number of nonreducing ends is determined by the number of branches (alpha 1,6 linkages). Because the number of nonreducing ends greatly exceeds the number of reducing ends in a collection of glycogen molecules, all of the degredation and synthesis of glycogen takes place at the nonreducing ends, thus maximizing the rate of degredation and synthesis
Account for the different structures of glycogen and cellulose.
cellulose is a linear polymer of glucose joined by beta 1,4 linkages (allows formation of linear polymer ideal for structural roles). Glycogen is a branched polymer with the main chain being formed by alpha 1,4 bonds (forms a helical structure, which allows the storage of many glucose moeities in a small space)
Describe the differences in various glycoproteins and their functions
Usually the protein component constitutes the bulk of the glycoprotein by mass. In contrast, proteoglycans and mucoproteins and predominantly CHO. Proteoglycans have glycosaminoglycans attached and play structural roles, as in cartilage and the ECM. Mucoproteins often serve as lubricants and have multiple CHO attached through an N-acetylgalactosamine moiety.
Differentiate between a glycoprotein and a lectin
A glycoprotein is a protein that is decorated with CHO. A lectin is a protein that specifically recognizes CHO. A lectin can also be a glycoprotein.
What is the role of glycosaminoglycan in cushioning provided by cartilage?
Because the glycosaminoglycan is heavily charged, it binds many water molecules. When cartilage is stressed, the water releases and cushions the impact. When you unstress the joint, the water rebinds.
The only glycosylation found in cytoplasmic or nuclear proteins is ______
O-GlcNAc
