Term
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Definition
| A molecule bound reversably by a protein |
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Term
| Lingans bind to complementary sites called- |
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Definition
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Term
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Definition
| A structural adaptation of the binding site of the protein for tighter ligand-protein binding |
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Term
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Definition
| A compound permanently associated with a protein that contributes to the proteins function |
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Term
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Definition
| Heme: complex organic ring structure, protoporphyrin IX with a bound single Fe2+ (ferrous state) |
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Term
| How many coordination bounds does the iron atom of heme have? |
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Definition
| 6 coordination bounds; 4 bounded to and in the plane of the flat porphyrin ring system, and 2 bound perpendicular to it |
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Term
| How are unwanted reactions of gasses with Fe2+ avoided with heme containing proteins? |
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Definition
| In heme containing proteins, the hemes are located deep within the protein structure, thus access to the 2 open coordinate bonds is restricted. |
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Term
Why is there colour change in blood?
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Definition
| The conjugated double bond system of heme causes strong light absorption. When O2 binds, it affects electron distribution and alters the absoption of light by heme. it causes colour change blue (O2 depleted) to bright red (O2 rich arterial blood) |
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Term
| Why is carbon monoxide super toxic? |
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Definition
| Carbon monoxide (and nitric oxide) have higher affinities for heme Fe2+ than oxygen. As a result, CO binds strongly to iron and is very hard to reverse thus making it toxic |
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Term
| Oxygen-Binding proteins are important for________ |
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Definition
| Oxygen storage and transport over long distances |
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Term
| Myoglobin has a single binding site for ______ |
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Definition
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Term
| What does myoglobin fascilitate? |
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Definition
| It fascilitates oxygen diffusion in muscle tissue |
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Term
| ____________ only has one molecule of heme. |
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Definition
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Term
| True or False: Proteins are dynamic molecules? |
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Definition
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Term
Binding sites must be complementary in at least 4 different ways, what are they?
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Definition
| Size, shape, charge, hydrophilic/hydrophobic properties |
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Term
| 4 key concepts in protein-ligand interactions are: |
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Definition
| reversible binding, regulation, conformational change, specificity |
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Term
| When a reaction involves 1 molecule, such as a _________ reaction, the reaction is __ order |
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Definition
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Term
| An association reaction is an example of a ___ order reaction. |
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Definition
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Term
| What is the funtion of myoglobin? |
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Definition
| to store oxygen in the muscle |
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Term
| Oxygen binds ____ to myogloblin, with a partial pressure (P50) of ________ |
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Definition
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Term
| _______ must be able to bind oxygen at high pressure |
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Definition
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Term
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Definition
| is on in which the binding of a ligand to one site affects the binding properties of another site on the same protein eg. Hb |
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Term
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Definition
4 pyrrole rings
A conjugated double bond system
4 N atoms that can bond with Fe
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Term
| what are porphyrin rings are conneceted by? |
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Definition
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Term
| how many segmants can globins be divded into? |
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Definition
| can be divided into 8 alpha-helical segments denoted: A-H |
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Term
| In globin, helices E-F form what? |
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Definition
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Term
| Describe the proximal histidine |
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Definition
| the proximal histidine is F8. It is one residue directly bonded to iron (5th coordination bond) |
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Term
| What is the distal histidine? Is it bonded to heme? |
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Definition
| E7 is the distal histidine, it is close but not bonded to heme |
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Term
| On what side doe oxygen bind to iron, proximal or distal? |
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Definition
| distal, the E7 side of the atom |
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Term
| How many amino acid residues does myoglobin have? |
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Definition
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Term
| how many amino acid residues are in α hemoglobin? how many are in β hemoglobin? |
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Definition
α hemoglobin has 141 a.a residues
β hemoglobin has 146 a.a residues |
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Term
| what type of interactions hold the subunits of hemoglobin together? |
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Definition
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Term
| Upon binding, what happens to α1:β1 interactions? what happens to α1:β2 interactions? |
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Definition
| α1:β1 interactions remain the same upon binding, but α1:β2 interactions change with broken salt bridges |
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Term
| When ligand and modulator are indentical they are called what? |
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Definition
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Term
| A hetertropic modulator is what? |
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Definition
when ligand and modulator are different
(can be activiators (+) or or inhibitors (-)) |
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Term
| for Hb, Give an example of a ligand and an activating homotropic modulator |
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Definition
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Term
| ______ has a sigmoidal O2-binding curve |
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Definition
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Term
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Definition
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Term
| What are the 2 models for cooperative binding of ligands to proteins with multiple binding sites? |
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Definition
The MWC (concerted model)
The Sequential model |
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Term
| Describe the MWC model of cooperative binding |
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Definition
| This model assumes that the subunit of a cooperatively binding protein are functionally identical. That all subunits undergo the transition form one conformation to the other simultaneously. No individual protein has individual subunit in different conformations (the 2 conformations are in equilibrium) is all or none |
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Term
| Describe the sequential model for cooperative bindinf of ligands and proteins |
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Definition
| Ligand binding can induce a chnage of conformation in an individual subunit. A conformational change in one subunit make s a similar change in an adjacent subunit as well as the binding of a seconf ligand. |
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Term
| Besides O2, what other by products of cellular respiration does hemoglobin transport? |
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Definition
| Hydrogen protons and Carbon dioxide |
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Term
| The reaction of CO2 being hydrated to form bicarbonate is catalyzed by what enzyme? |
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Definition
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Term
| Why is the conversion of CO2 to bicarbonate important to the regulation of O2 binding and release in blood? |
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Definition
| Because the hydration of CO2 results in an increase in the H+ concentration in the tissues and the binding of O2 by hemoglobin is significantly influenced by pH and CO2 concentration. Also if CO2 didn't change to bicarbonate, there would be bubbles in tissues and blood. |
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Term
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Definition
The Bohr effect states that hemoglobin's oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide
A decrease in blood pH or an increase in blood CO2 concentration will result in hemoglobin proteins releasing their loads of oxygen and a decrease in carbon dioxide or increase in pH will result in hemoglobin picking up more oxygen |
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Term
| Where does H+ bind to on the hemoglobin? |
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Definition
| H+ binds to any of the several amino acid residues on the protein |
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Term
| Fetal hemoglobin has a lower affinity for _____ which gives it a higher affinity for ______? |
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Definition
lower affinity for BPG -(Kd is higher that maternal Hb)
this gives a higher affinity for O2 -(Kd (p50) for O2 is lower than maternal Hb) |
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Term
| What are the differences between HbS (sickle cell) and HbA (regular)? |
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Definition
-In HbS, the Glu A3 on the β globin (glutamate β6) is changed to valine (Val,V).
-HbS tetramer has 2 fewer negative a.a.
-DeoxyHbS tetramers aggregate-abnormal hydrophobic interaction
-Sickle RBC contain long HbS fibers
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Term
| What are the 4 mechanisms of enzyme regulation? |
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Definition
1. allorstery - reversible, non-covalent binding of regulatory compounds (allorsteric modulators)
2. reversible, covalent modification - mediated by a seperate enzyme system
3. interactions with regulatory proteins
4. proteolyctiv cleavage
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Term
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Definition
| A regulatory enzyme with catalytic activity modulated by non-covalent binding of a specific metabolite at a site other than the active site |
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Term
| What are 4 properties that make allorsteric enzymes different from simple non-regulatory enzymes? |
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Definition
1. They are larger, structurally more complex - usually multisubunits
2. They have regulary (=allorsteric) sites - bind modulator
3. They undergo conformational change in response to modulator binding
4. They do not obey the Michaelis-Menten kinetics model |
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Term
| Aspertate Transcarbamoylase is an example of a _________ enzyme? |
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Definition
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Term
| How many polypeptide chains are associated with Aspertate Transcarbamoylase (ATCase)? |
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Definition
12 polypeptide chains,
2 Catalytic subunits (3 chains each) &
3 Regulatory subunits (2 chains each) |
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Term
| Why does ATCase have 12 polypeptide chains? |
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Definition
| to control the biosynthesis of pyrimidines (CMP, UMP) |
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Term
| What forms N-Carbamoylaspertate? |
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Definition
| carbamoyl phosphate and aspertate are catalyzes by ATCase |
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Term
| How many subunits does ATCase have? |
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Definition
5 subunits,
2 catalytic and 3 regulatory |
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Term
| What type of modulator is Aspartate? |
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Definition
| positive homotropic modulator |
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Term
| In ATCase synthesis, what does CTP (Cytidine triphosphate) do? |
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Definition
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Term
| What are the heterotropic modulators for ATCase? |
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Definition
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Term
| What location do the substrates bind to on ATCase? |
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Definition
| Substrates binds at the interface of catalytic side chains |
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Term
What location do the heterotropic modulators bind to on ATCase?
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Definition
| CTP and ATP bind to the regulatory side chains |
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Term
| Allorsteric effect of ATCase are a result of changes to what? |
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Definition
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Term
| In T state, ATCase has a more _________ conformation, resulting in ______ access for ______ |
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Definition
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Term
| In R state, ATCase has a more _________ conformation, resulting in ______ access for ______ |
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Definition
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Term
| CTP binding is favoured when ATCase is in which state? |
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Definition
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Term
| R state of ATCase favours _____ and _____ binding. |
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Definition
| ATP and substrate binding |
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Term
| N-(phosphonacetyl)-L-aspartate (PALA) is: |
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Definition
| A non-reactive bisubstrate analog that mimics the reaction intermediate of ATCAse |
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Term
| What are the structural changes during activation of ATCase when bound to PALA within the catalytic subunits? overall? |
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Definition
Within the catalytic subunits: Flexing at interfaces at Catalytic chains
Overall: Catalytic trimers move apart 12A and rotate relative to each other
Regulatory dimer rotate
Change in bend between Regulatory chains |
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Term
| In ATCase, what can induce T to R state conversion in the absence of substrate? |
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Definition
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Term
| In covalent modefication, what are the target residues of ADP-ribosylation? |
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Definition
| Arg, Gln, Cys, diphthamide (a modified His) |
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Term
| In covalent modefication, what are the target residues of phosphorylation? |
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Definition
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Term
| True or False-Phosphorylation is not sequence specific? |
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Definition
| False, it is sequence specific |
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Term
| The attachment of a phosphoryl group is catalyzed but what enzyme? |
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Definition
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Term
| What enzyme can remove a phosphoryl group? |
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Definition
| phosphoprotein phosphatase |
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Term
| What 4 changes do phosphorlyation introduce? |
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Definition
1. A relatively large group
2. A negative charge- allowing electrostatic interaction (attraction, repulsion)
3. A Change in H-bonding capacity
4. A site for protein-protein interactions |
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Term
| Glycogen phosphorlase is activated by what? |
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Definition
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Term
| Glycogen phosphorlase has ___ identical _____sites. |
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Definition
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Term
| Each subunit of glycogen phosphorylase is phosphorylated at _____ |
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Definition
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Term
| What enzyme is responsible for the synthesis of glycogen in mammalian cells? |
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Definition
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Term
| Glygogen synthase in _____ by phosphorylation |
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Definition
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Term
| In response to cAMP, PKA regulates many cellualr functions, such as: |
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Definition
1. Glycolysis
2. DNA condensation
3. Fatty acid metobolism
4. Glycogen metabolism
5. Cell surface ion channels |
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