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155 Cards in this Set

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Metabolism is a ? ? network?
complex 3-D network
In metabolism the concentration of any one intermediate has the ability to effect what?
has the ability to effect other intermediates...all intertwined
Name 6 possible fates of glucose 6-phosphate?
1. glycolysis

2. glucose

3. lipids

4. glycoproteins

5. other sugars

6. pentose phosphate pathway
4 subsections of metabolic regulation?
1. glycogen breakdown and synthesis

2. regulation and metabolic homeostasis

3. regulation of glycolysis and gluconeogenesis

4. regulation of glycogen breakdown and synthesis
Where is glycogen stored?
primarily in the liver and muscles
Glycogen is what percentage of a muscles mass?
approx. 1-2%
In the muscles what is glycogen a source of?
a quick source of energy (but not the initial source of energy)
The glycogen stored in the muscles can be exhausted in what amount of time?
in less than 1 hour
3 General Steps of Glycogen breakdown? (also state what else is occuring while these steps are happening)
1. Glycogen's monomers are removed sequentially, producing GLUCOSE 1-PHOSPHATE

2. DEBRANCH, producing GLUCOSE

3. CONVERT GLUCOSE 1-PHOSPHATE to GLUCOSE 6-PHOSPHATE (----> glycolysis)

(meanwhile in the liver: glycogen --> glu 6-P --> glucose)
What is glycogen broken down to?
1. glucose 1-phosphate

2. glucose
In the liver what is glycogen broken down to?
glucose
Glycogen synthesis is not just the reversal of what?
glycogen breakdown
The biosynthesis of many polysacch.s involves what?
sugar nucleotides
Name a sugar nucleotide that is a key intermediate for the synthesis of glycogen?
UDP-glucose
The formation of a sugar nucleotide is a ? ? process.
very exergonic
UDP-glucose could be called the "? ?" to the growing polymer.
glucose donor
Briefly describe the synthesis of UDP-glucose.
Glucose + ATP -> Glu 6-P + ADP
Glu 6-P -> Glu 1-P
Glu 1-P + UTP -> UDP glu + PPi
(exergonic)
(UDP glu is key intermediate form in exergonic process...goes on to form glycogen)
Where does glycogen synthesis occur?
in all cells, but esp. in the liver and muscle
In glycogen synthesis the primer must have at least 8 what?
glucose residues
How are gycogen branches synthesized?
A glycogen-branching enzyme transfers 6 or 7-mers from the non-reducing end of a chain to an 'interior' glucose of the chain (so essentially clips off one end of the straight chain and move it then reattaches it at a different point)...know that glycogen branching enzyme is reqd
What is glycogenin?
a protein primer and catalyst (so a beginning point and 'enzyme-like')...reqd for the initiation of glycogen synthesis and then glycogen synthase adds on next few glucose molecules
Once glycogen synthase is removed from the process of glycogen synthesis what occurs?
you are left with a glycogen molecule with a center of glycogenin
Other than the formation of glycogen, what else is UDP-glucose (a sugar nucleotide) involved in?
1. can combine with various non-polar drugs, toxins, and carcinogens

2. in plants: UDP-glu to UDP-glucuronate to ascorbic acid (vitamin C)...so precursor for vit c in plants

3. synthesis of lactose in mammals
So UDP-glucose can combine with various non-polar drugs, toxins, and carcinogens...what does it do once it combines with them?
converts them to polar deriv.s that are more easily cleared by the kidney to the urine. May lead to drug tolerance or toxin resistance.

-this is good for toxins (clears some from body)

-may be bad for drugs (b/c they are cleared)
When UDP-galactose is involved in the synthesis of lactose in mammals what enzyme is involved and when is it activated?
lactose synthase...activated post-partum
It is extremely important to ? and ? metabolism.
balance and regulate metaboilism
Artificial sweeteners are especially useful for what population?
diabetics
Generally speaking what needs to be regulated in metabolism?
1. Breakdown (yielding usable energy (eg. ATP)

VERSES

2. Synthesis (reqing energy)
Essentially what is a dynamic steady state?
equal rates of formation and breakdown...makes it seem that concentrations are remaining the same
What is the net effect of metabolic regulation and the dynamic steady state?
homeostasis (constant concentration, can be disturbed, then restored...essentially the maintaining of concentration)
Name the "key energy molecules".
1. ATP/(ADP/AMP)

2. NADH/(NAD+)

3. NADPH/ (NADP+)

4. Acetyl CoA
Of the energy molecules name the 4 that contain chemical energy in a bond that can be broken to release the energy?
1. ATP

2. NADH

3. NADPH

4. Acetyl CoA
The lower energy counterpart of ATP?
ADP / AMP
The lower energy counterpart of NADH?
NAD+
The lower energy counterpart of NADPH?
NADP+
What is the overall key role of AMP?
a "special role" as an indicator of metabolic status
Explain how AMP is an indicator of metabolic status?
A small decrease in the [ATP] leads to an equal increase in [AMP]....HOWEVER, if looked at as a percentage there is a huge difference, decrease in [ATP] is only a small increase percentage wise but leads to a huge increase (percentage wise) in [AMP] because the initial concentration is so small compared to ATP
What is the mass action ratio?
Q = [C][D]/[A][B]...can be used when a rxn is at equilibrium
What is the driving force behind most reactions in cells?
the tendency to strive for equilibrium
What is the difference between ^G'" verses ^G'?
^G'" (standard delta G) is a constant but ^G' depends on the concentration of the metabolites
If metabolite concentrations are approximately equal to equilibrium concentrations then what can be said about the reaction?
that it is near equilibrium, so ^G' is relatively small : the rxn proceeds to a limited extent
If metabolite conc.s are not equal to equilibrium concentrations then what occurs?
the rxn tends to strongly proceed....so the farther things are from equilibrium the stronger the tendency to strive for it
The concentration of enzymes in cells is usually different than ^G'". What does this tell us?
that the concentrations found in cells are important for the rxn moving forward
What rxns need to be regulated?
those with large ^G' need to be (and are) regulated...these include 1, 3, 10, and BP of glycolysis and gluconeogenesis
3 ways in which enzyme activity can be controlled?
1. by changing the number of active enzyme molecules in a cell

2. covalent modification

3. allosteric effectors
Explain how changing the number of active enzyme molecules controls enzyme activity? Explain 3 ways to effect this?
because the more enzymes we have the more rapid the rxn is...however this is actually a relatively slow way to control enzyme activity (seconds to hours)

1. synthesis (transcription, translation)

2. activation of inactive precursors (proenzymes)

3. degradation
Explain covalent modification and how it can control enzyme activity?
e.g. phosphorylation and dephosphorylation...takes seconds to minutes...add to or remove some group (phosphoro-, adenyl)...this is slightly more rapid than just changing the number of active enzymes
Explain how allosteric effectors control enzyme activity?
allosteric effectors interact with enzymes, change conformations, and either activate of inactivate...rapid, takes milliseconds
Glycolysis has a lot of overlap with what?
gluconeogenesis
What is the goal of regulating glycolysis?
regulate [ATP] (homeostasis)
What is usually regulated in glycolysis?
usually an exergonic step (1, 3, 10)
One way of controlling the regulation of glycolysis is by what?
controlling [substrate]
'Regulatable' enzymes in glycolysis work like a what? explain.
they work like a valve...regulate by allosteric mech. or hormone
The regualtion of glycolysis is often just after what?
a critical branch point
The regulation of glycolysis involves the coordinated regulation of what?
paired pathways (eg. glycolysis and gluconeogenesis)
The coord. regulation of glycolysis and gluconeogenesis involve how many common enzymes?
7
3 reactions of glycolysis are so ? they are essentially irreversible.
exergonic
The 3 very exergonic/~irreversible rxns of glycolysis? (include relevant enzymes)
Step #1 : hexokinase

Step #3 : phophorofructokinase (PFK-1)

Step #10 : pyruvate kinase

(these 3 rxns and their bypasses ordinarily need to be well regulated)
The 1st rxn of glycolysis is also the ? of gluconeogenesis.
the 3rd bypass
The 10th rxn of glycolysis is also the ? of gluconeogenesis.
the 1st bypass
The 3rd rxn of glycolysis is also the ? of gluconeogenesis.
the 2nd bypass
Enzyme involved in the regulation of step 1 of glycolysis?
hexokinase
Enzyme involved in the regulation of step 3 of glycolysis?
PFK-1
Enzyme involved in the regulation of step 10 of glycolysis?
pyruvate kinase
Step 1, 3, and 10 of glycolysis are very ?.
exergonic
Hexokinase is involved in step 1 of glycolysis. How many isozymes does it have?
4 (I-IV)
Which hexokinase isozymes are involved in the regulation of step 1 of glycolysis in muscle?
I-III
Describe the regulation of step 1 of glycolysis in muscle?
(inv.s hexo-I-III)...primary regulation is by feedback inh. of hexokinase by the rxn product GLUCOSE 6-PHOSPHATE (allosteric regulation of enzyme by product)...prevents use of more than is needed...ie. feedsback, binds to enzyme and slows down rxn because we have increased ATP and increased NADH so we get accumulation of glucose-6 phosphate and it feedsback and slows down glycolysis because we don't need anymore at the moment
Which isozyme of hexokinase is involved in the regulation of step 1 of glycolysis?
hexo-IV
Explain how step 1 of glycolysis is regulated in the liver?
primary regulation is by GLUCOSE (SUBSTRATE) concentration...prevents use when in short supply (so the most important thing is how much glucose is present)
Step 3 of glycolysis involves the regulation of what?
PFK-1
In step 3 of glycolysis what is the enzyme involved and what is the substrate? What is the allosteric inhibitor?
enzyme = PFK-1

substrate = fructose 6-phosphate

allosteric inh = high [ATP]
In the regulation of PFK-1 in glycolysis step 3 what does more substrate translate to? What else is a factor?
more enzyme...but ATP is also a factor (an increase in ATP lowers the curve...so as [ATP] increases rxn #3 slows down because you don't need more ATP)
Show the molecular formula for step 3 of glycolysis?
Fru 6-phosphate + ATP --> Fru 1,6-bisphosphate + ADP
How does PFK-1 regulation in step 3 of glycolysis react to an increase in ATP?
slows rxn down
How does PFK-1 regulation in step 3 of glycolysis react to an increase in AMP or ADP?
they activate the rxn (because an increase in them is correlated with a decrease in ATP)
How does PFK-1 regulation in step 3 of glycolysis react to an increase in citrate?
it slows the rxn down because it is related to a high level of activity in the citric acid cycle (which means an abundance of energy)
How does PFK-1 regulation in step 3 of glycolysis react to an increase in fructose 2, 6 bisphosphate?
activates the rxn (if the conc. was low it would indicate low enzyme activity)
The enzyme involved in step 10 of glycolysis?
pyruvate kinase
Step 10 of glycolysis is allosterically inhibited by what?
indicators of abundant energy supply : (an increase in either of these slows the rxn down)

1. ATP

2. Acetyl CoA
The 2 bypasses of gluconeogenesis work to regulate gluconeogenesis controlling and regulating what?
1. by controlling the fate of pyruvate

2. by regulating the activity of FBPase-1 (and coordinately regulating PFK-1)
When gluconeogenesis is regulated by controlling the fate of pyruvate what occurs when energy is abundant?
synthesize glucose
In gluconeogenesis regulation thru the control of the fate of pyruvate what happens when energy is needed?
catabolize Acetyl CoA
What does Acetyl CoA do to pyruvate with regards to the regulation of gluconeogenesis?
it regulates the fate of pyruvate...back to glucose if energy is not needed or to the citric acid cycly if energy is needed...
What does ATP do to PFK-1?
inhibits it
What does ADP do to PFK-1?
activates it
What does AMP do to PFK-1?
activates it
What does citrate do to PFK-1?
inhibits it
What does AMP do to FBPase-1?
slows it (bc an increase in AMP indicates a decrease in ATP and it slows down this rxn thus slowing all of gluconeogenesis)(This way glycolysis will take place and ATP will be produced)
The coordinate regulation of PFK-1 and FBPase-1 is what?
hormonal
What is the regulation of PFK-1 and FBPase mediated by?
fructose 2,6-bisphosphate
What does glucagon do to fructose 2,6-bisphosphate?
decrease it (which will inh. glycolysis and promote gluconeogenesis)
In the coordinated regulation of PFK-1 and FBPase what does low blood sugar lead to?
1. low bl. sugar

2. increases glucagon (pancreatic hormone)

3. decreases fru 2,6-BP

4. a. inactivates PFK-1
b. activates FBPase
PFK-1 activates what?
glycolysis
FBPase promotes what?
gluconeogenesis
In what rxn if fru 2,6-BP an intermediate in; glycolysis or gluconeogenesis?
not an intermediate in either one...just an "outsider"...activate PFK-1 and inh.s FBPase
A high conc. of fru 2,6-BP will activate ? and inhibit ?.
activates glycolysis and inh.s gluconeogenesis
In the absence of fru 2,6-BP you don't get much activation of this enzyme?
PFK-1
The absence of fru 2,6-BP is indicative of activation of this enzyme?
FBPase
When you have an increase in [glucagon] you get a decrease in what? Why?
decrease in fru 2,6-BP...because it is converted back to fru 6-phosphate
If opposing rxns of glycolysis and gluconeogenesis are coupled what can occur?
the can simply burn (waste) energy without putting it to good use...ordinarily this is prevented by coordinate reciprocal regulation (but in some circumstances coupling is allowed to proceed for a good reason)
What is a "futile" cycle? give ex.
a pair of rxns with no net value, just burns up energy and produces some heat...sometimes seen in bumblebees

ex)

ATP + H2O --> ADP + Pi
The coordinated regulation of glycogen breakdown and synthesis involves what?
1. breakdown : inv.s glycogen phosphorylase

2. synthesis : inv.s glycogen synthase ("synthesis")
Show the rxn involving glycogen phosphorylase?
(the reg. of glycogen catabolism)

glycogen --(glycogen phosphorylase)--> glucose 1-phosphate
How can glycogen phosphorylase exist?
in a more active or less active state
The more active state of glycogen phosphorylase is what?
phosphorylated
The less active state of glycogen phophorylase is what?
not phosphorylated
What phosphorylates glycogen phosphorylase? What does this do?
a kinase enzyme...activates it
What activates the kinase enzyme that phosphorylates glycogen phosphorylase?
epinephrine, glucagon (low blood sugar), and Ca2+
What blocks the activation of the kinase that phosphorylates glycogen phosphorylase?
ATP
What can further activate glycogen phosphorylase?
AMP
What can dephosphorylate the glycogen phosphorylase enzyme?
phosphatase (this deactivates it)
When glycogen phosphorylase is active what does it do?
catalyzes the 1st step of glycogen breakdown
A low bl. sugar leads to a rise in what?
glucagon
The active form of glycogen phosphorylase has ? ? sites.
glucose receptor
How does an increase in the conc. of insulin effect glycogen phosphorylase?
causes it to move to a less active form
Glycogen phosphorylase breaks down glycogen to yield what?
glucose 1-phosphate
glycogen phophorylase is activated by what?
1. glucagon (liver)

2. Epinephring (muscle)

3. Ca2+, AMP (muscle)
glycogen phophorylase is inactivated by what?
1. glucose

2. insulin
glycogen phophorylase activation is prevented by what?
ATP (b/c if you have it in cells you don't need to breakdown more glucose)
Which enzyme is involved in the regulation of glycogen SYNTHESIS?
glycogen synthase
The active form of glycogen synthase?
not phosphorylated
The inactive form of glycogen synthase?
phosphorylated
What inactivates glycogen synthase?
many protein kinases BUT the most important is glycogen synthase kinase 3 (GSK 3)
GSK 3 is becoming a popular what?
drug target
What does GSK 3 do?
converts active glycogen synthase to inactive form
What is the key mediator in the regulation of glycogen synthase?
insulin...inactivates glycogen synthase by blocking GSK 3
What activates glycogen synthase?
PP1 (phosphoprotein phosphatase)
3 things that activate PP1 and lead to the activation of glycogen synthase?
1. insulin

2. glucose 6-phosphate

3. glucose
2 things that inactivates PP1 thus inactivating glycogen synthase?
glucagon and epinephrine
What inactivates GSK 3 thus blocking the inactivation of glycogen synthase?
insulin
What 4 things lead to glycogen synthase being more active?
1. PP1 activation by glucose

2. PP1 activation by glu 6-phosphate

3. PP1 activation by insulin

4. GSK 3 inactivation by insulin
2 things that lead to a less active form of glycogen synthase?
2. PP1 blocked by glucagon

2. PP1 blocked by epinephrine
5 general factors that affect the response to immunogens?
1. amt of immunogen

2. route of exposure

3. genotype of recipient

4. repetition

5. adjuvant
How does the amt of immunogen affect the response to immunogens?
In excessively large doses it can lead to intolerance and too little will not elicit a response.
Give an example of how the route of exposure affect the response to immunogens?
oral exposure evokes a different response than parenteral exposure (all types of exposures give an unique response)
List 4 different routes of exposure?
1. IV (goes to spleen)

2. IM (goes to lymph nodes)

3. SC (goes to lymph nodes)

4. oral route (goes to gut mucosa)
How does the genotype of the recipient affect the response to immunogens?
The recipients type of MHC, B-cell and T-cell genes will influence the degree of reactivity or if you will have no reaction.
Explain how repetition affects the response to immunogen?
Boosting tends to increase the response. It is important to give progressively more. You do not have an allergic reaction the first time you are exposed to something.
How do adjuvants affect the response to immunogens?
Admin. with other immunogens or adjuvants can alter the immune response. These are often used in studies but not in people. Adjuvants are substances that when mixed with and co-injected with Ag enhance the immunogenicity of that Ag.
The only adjuvant approved by the FDA for use?
alum
4 effects of adjuvant?
1. Ag persistence is prolonged

2. Co-stimulatory signals are increased

3. local inflammation is increased

4. nonspecific proliferation of lymphocytes in the stimulated area of injection
2 examples of Adjuvants?
1. alum

2. freund's adjuvant
4 points about alum?
1. only adjuvant approved for human use

2. causes time of exposure to Ag to increase from days to weeks (so increases exposure time and slows immune response time down)

3. increases size of Ag making it amenable to phagocytosis (so kind of acts like a carrier and allows phagocytosis to occur quicker)

4. like most adjuvants it can cause granulomas
What is a granuloma?
Occur when macrophages flow to the area of an adjuvant and form a cluster. A rich mass of cells with a "lumpy" appearance.
What is the typical adjuvant used in the lab?
Freund's adjuvant
Why are adjuvants used in studies?
They are used because they make immunological studies appear more effective than they actually are.
Epitopes are ? determinants.
antigenic
What do large molecules do?
They induce an immune response.
What is an epitope?
Part of a macromolecule. It is usually non-self. This means that is is typically recognized by an immune system cell. So these are essentially the areas of an Ag that are recognized by the immune system. The whole molecule is not recognized, just the antigenic epitope.
An Ag may contain several distinct ?.
epitopes
Ab or TCR will target how many epitopes?
EACH one will only target one epitope.
What is the percentage of the total surface area of a protein is taken up by ONE epitope?
10%
Why must Epitopes and Abs have complementary shapes?
For short-range binding forces (van der waals)
Where are epitopes developed?
In the marrow for B-cells and in the thymus for T-cells.