Week 8: Signaling Proteins, Carbohydrates Flashcards
A polysaccharide is a polymer of ______, which are compounds that contain a single _______ and several ________.
simple sugars
carbonyl group
hydroxyl groups
A furanose is a ______ sugar that contains a _____ similar to that in furan
cyclic
five-membered ring
A pyranose is a ______ sugar that contains a ______ similar to that in pyran.
cyclic
six-membered ring
An aldose is a sugar that contains an _____; a ketose is a sugar that contains a ______.
aldehyde group
ketone group
A glycosidic bond is the acetal linkage that joins ______.
two sugars
An oligosaccharide is a compound formed by the linking of several _____ by _____.
simple sugars (monosaccharides)
glycosidic bonds
A glycoprotein is formed by the covalent bonding of _____ to a _____.
sugars, protein
There are ______ chiral centers in the open-chain form of glucose. Cyclization introduces another chiral center at the carbon involved in hemiacetal formation, giving a total of _____ chiral centers in the cyclic form.
four (carbons two through five)
five
Two sugars are epimers of each other. Is it possible to convert one to the other without breaking covalent bonds?
Converting a sugar to an epimer requires inversion of configuration at a chiral center. This can be done only by ______ covalent bonds.
breaking and reforming
A reducing sugar is one that has a _______. The _____ is easily oxidized, thus reducing the oxidizing agent.
free aldehyde group
aldehyde
Glycoproteins are ones in which _____ are covalently bonded to ______. They play a role in ______, frequently as recognition sites for external molecules. _____are glycoproteins.
carbohydrates, proteins
eukaryotic cell membranes
Antibodies (immunoglobulins)
How many chemical bonds are broken at the anomeric carbon when β-D-galactose is converted to the open chain form?
What happens to the hybridization of the anomeric carbon when it is converted to the open-chain form?
What kind of isomerism is demonstrated by the alpha and beta forms of D-galactose ?
1; The carbon-oxygen bond is broken at the anomeric carbon.
It changes from sp3 to sp2.
stereoisomerism
Thus, for D-glucose, there are three possible D-sugars that are epimers:
There is only one possible L-sugar:
D-mannose, D-allose, and D-galactose
L-idose
Monosaccharides must be in the ______ to react with reducing agents. The cyclic hemiacetal form can mutarotate to the open-chain form, at which point the monosaccharide can be reduced.
open-chain form
3 major classes of membrane receptors:
- Seven-transmembrane-helix receptors associated with
heterotrimeric G-proteins. (7TM) - Dimeric membrane receptors that recruit protein kinases.
- Dimeric protein receptors that are protein kinases.
Big idea: the transmembrane protein (the receptor protein) changes _______, which transfers ______ across the membrane.
conformation
signal
Conformational Change of 7TM causes Activation of _____ by a ______ Pathway
Protein Kinase A
G-protein
Kinases are enzymes that _______ a substrate at the expense of a ______
phosphorylate
molecule of ATP
A key component of the EGF pathway, as well as other signal-transduction pathways, is the _______.
protein Ras
Ras is a member of the family of signal proteins called _______ or _____. The _______ are _______.
small G proteins, small GTPases
small G proteins
monomeric
Like the Gα protein, Ras is _____ when bound to ____ and _____ when bound to ____. Ras also has intrinsic ________, which controls signal duration.
active , GTP
inactive, GDP
GTPase activity
The polypeptide hormone insulin is secreted when the blood is rich in _____.
glucose
Insulin is the biochemical signal for the _____.
fed state
Insulin consists of two polypeptide chains linked by _________.
disulfide bonds
Unlike the other members of the receptor tyrosine kinase class, the insulin receptor exists as a _____ even in the absence of insulin
dimer
Intrinsic GTPase activity means it can revert back to the ________ on its own
inactive form
Monosaccharides are ______ or ______ that contain two or more _____ groups.
* The smallest monosaccharides are composed of _______.
aldehydes, ketones
alcohol
three carbons
Constitutional isomers differ in the order of _______ of atoms
attachment
Stereoisomers are atoms connected in the same _____ but differ in ______
order, spatial arrangement
Enantiomers are _________ mirror images
nonsuperimposable
Diastereoisomers are isomers that are not ______ images
mirror
Epimers differ at ____ of several asymmetric carbon atoms
one
Anomers are isomers that differ at a _____ asymmetric carbon atom formed on ______
new asymmetric carbon
ring closure
The chemical basis for ring formation is that an aldehyde can react with an alcohol to form a ______, whereas a ketone can react with an alcohol to form a ______
hemiacetal
hemiketal
The a form means that the hydroxyl at C-1 is ____ the plane of the ring (______ the C-6 carbon)
below
opposite
The beta form means that the hydroxyl at C-1 is ____ the plane of the ring (______ the C-6 carbon)
above
same side as
β- D -glucopyranose adopts the chair conformation because the axial positions are occupied by hydrogen atoms, reducing ________.
steric hindrance
Because the two anomeric forms of glucose are in an equilibrium that passes through an open-chain form, the _______ form reacts with oxidizing agents.
free open-chain
A bond formed between the anomeric
carbon atom of glucose and a _____
group of another molecule is called an ______, and the product is called a _______.
hydroxyl
O-glycosidic bond
glycoside
A bond formed between the anomeric
carbon atom of glucose and an amine is
called an _________.
N-glycosidic bond
Glycogen and Starch Are Storage Forms of Glucose also called
polysaccharides, complex carbohydrates or glycans
Glycoproteins are predominantly _____ but have oligosaccharides covalently linked through _______
protein
N or O-glycosidic bonds
Mucins are about 1/2 _____ and 1/2 ________
protein, polysaccharide
Proteoglycans are mostly _______ with a small ______ core covalently linked by ________.
polysaccharide
protein
N or O glycosidic linkages.
In all classes of glycoproteins, carbohydrates are attached to the nitrogen atom in the side chain of _____ or to the oxygen atom of the side chain of _______.
asparagine (N-linkage)
serine or threonine (O-linkage).
Glycoproteins
All N-linked polysaccharides consist of a
common pentasaccharide core consisting of:
– three mannoses
– a six-carbon sugar
– and two N-acetylglucosamine units.
Proteoglycans are proteins attached to
_______, which make up 95% of the proteoglycan by weight.
- Glycosaminoglycans are composed of repeating units of a disaccharide, one of which is a derivative of an ______ and one of which carries a ______, either as a ________.
- Proteoglycans are key components of the extracellular matrix and serve as lubricants.
glycosaminoglycans
amino sugar
negative charge
carboxylate or sulfate
Mucins are _______
proteins that have long stretches of _______ amino acids to which ________ are linked.
very high molecular weight
serine and threonine
o-linked oligosaccharides
Mucins are composed of about 50%
_______ saccharides and 50%
_______ saccharides.
– Hold water, but not as much as the
_______
negatively charged
neutral
proteoglycans
____ and _____ will bind to G-proteins, but _____ will not
GDP, GTP
cAMP
Which of the following is NOT a secondary messenger?
cAMP
Epinephrine
Ca2+
IP3
Epinephrine
Cross phosphorylation is best described as the kinase activity of one monomer unit acting on the analogous monomer unit in the _____ in the context of tyrosine kinase receptors.
same receptor dimer
General steps of a G protein-coupled receptor pathway:
- Ligand binds to the receptor
- Conformational change of the receptor
- Dissociation of β and γ subunits of the G protein and the exchange of GDP for GTP in the G protein
- Adenylate cyclase converts ATP to cAMP
- Kinase protein is activated to phosphorylate targets
The RAS protein plays a similar role in biosignaling pathways to ______
Heterotrimeric G protein
Binding of a ligand to a receptor tyrosine kinase causes _______ of the receptor, which then _____ the next protein in the signaling pathway.
phosphorylation
phosphorylates
The secondary messenger cAMP is produced by the enzyme ______.
Adenylate cyclase
What enzyme is activated by association with an active G protein?
Adenylate cyclase
Proteoglycans are composed primarily of ______ in the form of ______, which are
repeating units of a _____. They have a structural role in cells in the ______ and can also function as _______.
carbohydrates
glycosaminoglycans
disaccharide amino sugar
extracellular matrix
lubricants
Mucins are a 50:50 ratio of ________. Contain long chains of _____ residues that will O-link _______. Exact carbohydrate composition is highly _____, but commonly have functions in ________, and of course, the production of _____!
protein and carbohydrate
serine/threonine (accessible -OH groups!)
oligosaccharides
variable
protection lubrication
mucous
Glycoproteins are composed primary of ________. Because of their composition they have a variety of functions within the cell/body, but they are often found as ______ and in the immune system as ______; they are excellent for finding and binding to things because of their ______ portion
proteins
cell receptors
antibodies
protein
The human ABO blood groups reflect the specificity of ________.
glycosyltransferases
All of the blood groups share the ______ foundation called O.
oligosaccharide
In A, ________ is added to the O by a specific _______.
N-acetylgalactosamine
glycosyltransferase
In B, ______ is added by another ______
galactose
glycosyltransferase
The blood type O produces no…
active glycosyltransferase
Glycosyltransferases place _______ onto the ‘base’ _______ antigen. Each glycosyltransferase is specific to a particular functional group and will therefore form its own…
functional groups
oligosaccharide O
unique antigen (one transferase makes
the A antigen and another makes the B antigen).
The O blood type will not produce any ______, so there is no creation of ______. This explains why the
O blood type (specifically O negative) is known as the ‘universal donor’ since there is no ________
that the body can detect. When the body is looking for foreign invaders, it is looking for nonself antigens, but
since every blood cell has the O antigen as a base, it will always be recognized as ‘safe’ and not rejected.
transferases, A/B antigens
antigen modification
The _______ present in proteoglycans will allow these molecules to also hold _____ in their structures,
which is how cartilage carries out its function of ______ many parts of our bodies. The water can act as a
_____ to absorb shock and prevent the malformation of body parts such as the nose and ears because their shape is
vital to their function. The ________ can additionally act as a compression ‘spring’ to help absorb impact as well since the _____ will provide a small reactive force to any compression that takes place.
negative charges
water
‘cushioning’
pad
aggregation of negative charges
repulsion
Why do sugars have the ability to make so many derivatives of the sugar molecules?
The _______ groups on sugars are very favorable for organic reactions – for instance, alcohols are great candidates for _________. Amine groups can also perform nucleophilic attacks to replace the ______ on these sugars (______ is usually responsible for these N-linkages)
alcohol / carbonyl
ester/ether bonds (phosphates, Ser, Thr)
-OH groups
asparagine
1) Epinephrine binds to _____ receptor and induces a
conformational changes in the _____ structure
2) This conformational change leads to ____ replacing ____ on
the _____ subunit
3) When the ____ binds, further conformational changes will
take place and cause the ______ to dissociate.
4) The ______ will move towards _______ in
the membrane and activate it so that it can begin catalyzing the reaction of _______
5) _____ will then activate _______, which will go on to activate its intended targets
B-adrenergic, 7TM
GTP, GDP, alpha
GTP, beta and gamma subunits
active G-protein, adenylate cyclase
ATP -> cyclic AMP
cAMP, Protein Kinase A
If we mutate the binding region for adenylate cyclase, the _____ will not be able to bind to ______ and activate it. This will lead to the pathway being effectively inert as we will have ________ but they will not be able to activate their targets.
active G-protein
adenylate cyclase
active G-proteins
When GTP is bound, it will predictably be ______ and act on its targets further on in the pathway.
active (since G-proteins, in general, are active when bound to GTP)
- The ligand binds to the ______ portion of the EGF receptor, causing the ______ domains to ______. This dimerization triggers a _______ in the ______ domain, which also dimerizes.
- The _______ leads to cross-phosphorylation of the receptor’s _____, activating it.
- The activated _____ creates a binding site for _____ which undergoes a _______ that allows it to bind ______.
- ______ then induces a conformational change in _____, a small G-protein, enabling ______ to bind ____ and displace _____, activating Ras to target _____ in the signaling pathway.
extracellular, extracellular, dimerize, conformational change, intracellular
intracellular dimerization, kinase
kinase, Grb-2, conformational change, Sos
Sos, Ras, Ras, GTP, GDP, downstream molecules
1) Seven-transmembrane-helix receptors
- This receptor contains ______ that span the _____. Ligands bind to the ______ and promotes activation of a ______ by a conformational change for ________
seven helices
membrane bilayer
7TM
g-protein
downstream signaling
2) Dimeric receptors that ______ protein kinases: These receptors exist in monomers or dimers, depending on their activation. They have an intracellular component and an extracellular component. Binding of a ligand to the extracellular component of the receptor leads to ______ of the receptor and thus its activation by ______ also the intracellular component. Oftentimes this brings together _____ that, upon dimerization, are ______ and will begin acting on their specific targets in the pathway
recruit
dimerization, bringing together
two kinases
activated
3) Dimeric receptors that are protein kinases
-These receptors exist in a separated form or can already be in the dimeric form (such as in the case of insulin). Ligand binding to the extracellular component triggers receptor dimerization, bringing the intracellular components together. This typically activates associated cross-phosphorylation of _______ found on the receptor, which then _______ specific targets in the signaling pathway.
tyrosine kinases
phosphorylate
In this pathway, when insulin is bound it will activate a cascade that causes _______ of the receptor kinase that will activate ________. This will activate phosphoinositide-3-kinase, which will phosphorylate ____ into ______. This _____ then acts on PIP3-dependent kinase 1 (PDK1) that will phosphorylate and activate _____, which will finally lead to the production of _____ into the membrane for cells to take in more glucose.
cross-phosphorylation
Insulin Receptor Signal proteins (IRS proteins)
PIP2, PIP3, PIP3
Akt
GLUT4 transporters
