Biochm Ii: Met. Reg. Focus On Glucose And Glycogen (Test 1)

Front 1

Metabolism is a ? ? network?

Back 1

complex 3-D network

Front 2

In metabolism the concentration of any one intermediate has the ability to effect what?

Back 2

has the ability to effect other intermediates...all intertwined

Front 3

Name 6 possible fates of glucose 6-phosphate?

Back 3

1. glycolysis

2. glucose

3. lipids

4. glycoproteins

5. other sugars

6. pentose phosphate pathway

Front 4

4 subsections of metabolic regulation?

Back 4

1. glycogen breakdown and synthesis

2. regulation and metabolic homeostasis

3. regulation of glycolysis and gluconeogenesis

4. regulation of glycogen breakdown and synthesis

Front 5

Where is glycogen stored?

Back 5

primarily in the liver and muscles

Front 6

Glycogen is what percentage of a muscles mass?

Back 6

approx. 1-2%

Front 7

In the muscles what is glycogen a source of?

Back 7

a quick source of energy (but not the initial source of energy)

Front 8

The glycogen stored in the muscles can be exhausted in what amount of time?

Back 8

in less than 1 hour

Front 9

3 General Steps of Glycogen breakdown? (also state what else is occuring while these steps are happening)

Back 9

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)

Front 10

What is glycogen broken down to?

Back 10

1. glucose 1-phosphate

2. glucose

Front 11

In the liver what is glycogen broken down to?

Back 11

glucose

Front 12

Glycogen synthesis is not just the reversal of what?

Back 12

glycogen breakdown

Front 13

The biosynthesis of many polysacch.s involves what?

Back 13

sugar nucleotides

Front 14

Name a sugar nucleotide that is a key intermediate for the synthesis of glycogen?

Back 14

UDP-glucose

Front 15

The formation of a sugar nucleotide is a ? ? process.

Back 15

very exergonic

Front 16

UDP-glucose could be called the "? ?" to the growing polymer.

Back 16

glucose donor

Front 17

Briefly describe the synthesis of UDP-glucose.

Back 17

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)

Front 18

Where does glycogen synthesis occur?

Back 18

in all cells, but esp. in the liver and muscle

Front 19

In glycogen synthesis the primer must have at least 8 what?

Back 19

glucose residues

Front 20

How are gycogen branches synthesized?

Back 20

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

Front 21

What is glycogenin?

Back 21

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

Front 22

Once glycogen synthase is removed from the process of glycogen synthesis what occurs?

Back 22

you are left with a glycogen molecule with a center of glycogenin

Front 23

Other than the formation of glycogen, what else is UDP-glucose (a sugar nucleotide) involved in?

Back 23

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

Front 24

So UDP-glucose can combine with various non-polar drugs, toxins, and carcinogens...what does it do once it combines with them?

Back 24

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)

Front 25

When UDP-galactose is involved in the synthesis of lactose in mammals what enzyme is involved and when is it activated?

Back 25

lactose synthase...activated post-partum

Front 26

It is extremely important to ? and ? metabolism.

Back 26

balance and regulate metaboilism

Front 27

Artificial sweeteners are especially useful for what population?

Back 27

diabetics

Front 28

Generally speaking what needs to be regulated in metabolism?

Back 28

1. Breakdown (yielding usable energy (eg. ATP)

VERSES

2. Synthesis (reqing energy)

Front 29

Essentially what is a dynamic steady state?

Back 29

equal rates of formation and breakdown...makes it seem that concentrations are remaining the same

Front 30

What is the net effect of metabolic regulation and the dynamic steady state?

Back 30

homeostasis (constant concentration, can be disturbed, then restored...essentially the maintaining of concentration)

Front 31

Name the "key energy molecules".

Back 31

1. ATP/(ADP/AMP)

2. NADH/(NAD+)

3. NADPH/ (NADP+)

4. Acetyl CoA

Front 32

Of the energy molecules name the 4 that contain chemical energy in a bond that can be broken to release the energy?

Back 32

1. ATP

2. NADH

3. NADPH

4. Acetyl CoA

Front 33

The lower energy counterpart of ATP?

Back 33

ADP / AMP

Front 34

The lower energy counterpart of NADH?

Back 34

NAD+

Front 35

The lower energy counterpart of NADPH?

Back 35

NADP+

Front 36

What is the overall key role of AMP?

Back 36

a "special role" as an indicator of metabolic status

Front 37

Explain how AMP is an indicator of metabolic status?

Back 37

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

Front 38

What is the mass action ratio?

Back 38

Q = [C][D]/[A][B]...can be used when a rxn is at equilibrium

Front 39

What is the driving force behind most reactions in cells?

Back 39

the tendency to strive for equilibrium

Front 40

What is the difference between ^G'" verses ^G'?

Back 40

^G'" (standard delta G) is a constant but ^G' depends on the concentration of the metabolites

Front 41

If metabolite concentrations are approximately equal to equilibrium concentrations then what can be said about the reaction?

Back 41

that it is near equilibrium, so ^G' is relatively small : the rxn proceeds to a limited extent

Front 42

If metabolite conc.s are not equal to equilibrium concentrations then what occurs?

Back 42

the rxn tends to strongly proceed....so the farther things are from equilibrium the stronger the tendency to strive for it

Front 43

The concentration of enzymes in cells is usually different than ^G'". What does this tell us?

Back 43

that the concentrations found in cells are important for the rxn moving forward

Front 44

What rxns need to be regulated?

Back 44

those with large ^G' need to be (and are) regulated...these include 1, 3, 10, and BP of glycolysis and gluconeogenesis

Front 45

3 ways in which enzyme activity can be controlled?

Back 45

1. by changing the number of active enzyme molecules in a cell

2. covalent modification

3. allosteric effectors

Front 46

Explain how changing the number of active enzyme molecules controls enzyme activity? Explain 3 ways to effect this?

Back 46

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

Front 47

Explain covalent modification and how it can control enzyme activity?

Back 47

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

Front 48

Explain how allosteric effectors control enzyme activity?

Back 48

allosteric effectors interact with enzymes, change conformations, and either activate of inactivate...rapid, takes milliseconds

Front 49

Glycolysis has a lot of overlap with what?

Back 49

gluconeogenesis

Front 50

What is the goal of regulating glycolysis?

Back 50

regulate [ATP] (homeostasis)

Front 51

What is usually regulated in glycolysis?

Back 51

usually an exergonic step (1, 3, 10)

Front 52

One way of controlling the regulation of glycolysis is by what?

Back 52

controlling [substrate]

Front 53

'Regulatable' enzymes in glycolysis work like a what? explain.

Back 53

they work like a valve...regulate by allosteric mech. or hormone

Front 54

The regualtion of glycolysis is often just after what?

Back 54

a critical branch point

Front 55

The regulation of glycolysis involves the coordinated regulation of what?

Back 55

paired pathways (eg. glycolysis and gluconeogenesis)

Front 56

The coord. regulation of glycolysis and gluconeogenesis involve how many common enzymes?

Back 56

7

Front 57

3 reactions of glycolysis are so ? they are essentially irreversible.

Back 57

exergonic

Front 58

The 3 very exergonic/~irreversible rxns of glycolysis? (include relevant enzymes)

Back 58

Step #1 : hexokinase

Step #3 : phophorofructokinase (PFK-1)

Step #10 : pyruvate kinase

(these 3 rxns and their bypasses ordinarily need to be well regulated)

Front 59

The 1st rxn of glycolysis is also the ? of gluconeogenesis.

Back 59

the 3rd bypass

Front 60

The 10th rxn of glycolysis is also the ? of gluconeogenesis.

Back 60

the 1st bypass

Front 61

The 3rd rxn of glycolysis is also the ? of gluconeogenesis.

Back 61

the 2nd bypass

Front 62

Enzyme involved in the regulation of step 1 of glycolysis?

Back 62

hexokinase

Front 63

Enzyme involved in the regulation of step 3 of glycolysis?

Back 63

PFK-1

Front 64

Enzyme involved in the regulation of step 10 of glycolysis?

Back 64

pyruvate kinase

Front 65

Step 1, 3, and 10 of glycolysis are very ?.

Back 65

exergonic

Front 66

Hexokinase is involved in step 1 of glycolysis. How many isozymes does it have?

Back 66

4 (I-IV)

Front 67

Which hexokinase isozymes are involved in the regulation of step 1 of glycolysis in muscle?

Back 67

I-III

Front 68

Describe the regulation of step 1 of glycolysis in muscle?

Back 68

(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

Front 69

Which isozyme of hexokinase is involved in the regulation of step 1 of glycolysis?

Back 69

hexo-IV

Front 70

Explain how step 1 of glycolysis is regulated in the liver?

Back 70

primary regulation is by GLUCOSE (SUBSTRATE) concentration...prevents use when in short supply (so the most important thing is how much glucose is present)

Front 71

Step 3 of glycolysis involves the regulation of what?

Back 71

PFK-1

Front 72

In step 3 of glycolysis what is the enzyme involved and what is the substrate? What is the allosteric inhibitor?

Back 72

enzyme = PFK-1

substrate = fructose 6-phosphate

allosteric inh = high [ATP]

Front 73

In the regulation of PFK-1 in glycolysis step 3 what does more substrate translate to? What else is a factor?

Back 73

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)

Front 74

Show the molecular formula for step 3 of glycolysis?

Back 74

Fru 6-phosphate + ATP --> Fru 1,6-bisphosphate + ADP

Front 75

How does PFK-1 regulation in step 3 of glycolysis react to an increase in ATP?

Back 75

slows rxn down

Front 76

How does PFK-1 regulation in step 3 of glycolysis react to an increase in AMP or ADP?

Back 76

they activate the rxn (because an increase in them is correlated with a decrease in ATP)

Front 77

How does PFK-1 regulation in step 3 of glycolysis react to an increase in citrate?

Back 77

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)

Front 78

How does PFK-1 regulation in step 3 of glycolysis react to an increase in fructose 2, 6 bisphosphate?

Back 78

activates the rxn (if the conc. was low it would indicate low enzyme activity)

Front 79

The enzyme involved in step 10 of glycolysis?

Back 79

pyruvate kinase

Front 80

Step 10 of glycolysis is allosterically inhibited by what?

Back 80

indicators of abundant energy supply : (an increase in either of these slows the rxn down)

1. ATP

2. Acetyl CoA

Front 81

The 2 bypasses of gluconeogenesis work to regulate gluconeogenesis controlling and regulating what?

Back 81

1. by controlling the fate of pyruvate

2. by regulating the activity of FBPase-1 (and coordinately regulating PFK-1)

Front 82

When gluconeogenesis is regulated by controlling the fate of pyruvate what occurs when energy is abundant?

Back 82

synthesize glucose

Front 83

In gluconeogenesis regulation thru the control of the fate of pyruvate what happens when energy is needed?

Back 83

catabolize Acetyl CoA

Front 84

What does Acetyl CoA do to pyruvate with regards to the regulation of gluconeogenesis?

Back 84

it regulates the fate of pyruvate...back to glucose if energy is not needed or to the citric acid cycly if energy is needed...

Front 85

What does ATP do to PFK-1?

Back 85

inhibits it

Front 86

What does ADP do to PFK-1?

Back 86

activates it

Front 87

What does AMP do to PFK-1?

Back 87

activates it

Front 88

What does citrate do to PFK-1?

Back 88

inhibits it

Front 89

What does AMP do to FBPase-1?

Back 89

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)

Front 90

The coordinate regulation of PFK-1 and FBPase-1 is what?

Back 90

hormonal

Front 91

What is the regulation of PFK-1 and FBPase mediated by?

Back 91

fructose 2,6-bisphosphate

Front 92

What does glucagon do to fructose 2,6-bisphosphate?

Back 92

decrease it (which will inh. glycolysis and promote gluconeogenesis)

Front 93

In the coordinated regulation of PFK-1 and FBPase what does low blood sugar lead to?

Back 93

1. low bl. sugar

2. increases glucagon (pancreatic hormone)

3. decreases fru 2,6-BP

4. a. inactivates PFK-1
b. activates FBPase

Front 94

PFK-1 activates what?

Back 94

glycolysis

Front 95

FBPase promotes what?

Back 95

gluconeogenesis

Front 96

In what rxn if fru 2,6-BP an intermediate in; glycolysis or gluconeogenesis?

Back 96

not an intermediate in either one...just an "outsider"...activate PFK-1 and inh.s FBPase

Front 97

A high conc. of fru 2,6-BP will activate ? and inhibit ?.

Back 97

activates glycolysis and inh.s gluconeogenesis

Front 98

In the absence of fru 2,6-BP you don't get much activation of this enzyme?

Back 98

PFK-1

Front 99

The absence of fru 2,6-BP is indicative of activation of this enzyme?

Back 99

FBPase

Front 100

When you have an increase in [glucagon] you get a decrease in what? Why?

Back 100

decrease in fru 2,6-BP...because it is converted back to fru 6-phosphate

Front 101

If opposing rxns of glycolysis and gluconeogenesis are coupled what can occur?

Back 101

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)

Front 102

What is a "futile" cycle? give ex.

Back 102

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

Front 103

The coordinated regulation of glycogen breakdown and synthesis involves what?

Back 103

1. breakdown : inv.s glycogen phosphorylase

2. synthesis : inv.s glycogen synthase ("synthesis")

Front 104

Show the rxn involving glycogen phosphorylase?

Back 104

(the reg. of glycogen catabolism)

glycogen --(glycogen phosphorylase)--> glucose 1-phosphate

Front 105

How can glycogen phosphorylase exist?

Back 105

in a more active or less active state

Front 106

The more active state of glycogen phosphorylase is what?

Back 106

phosphorylated

Front 107

The less active state of glycogen phophorylase is what?

Back 107

not phosphorylated

Front 108

What phosphorylates glycogen phosphorylase? What does this do?

Back 108

a kinase enzyme...activates it

Front 109

What activates the kinase enzyme that phosphorylates glycogen phosphorylase?

Back 109

epinephrine, glucagon (low blood sugar), and Ca2+

Front 110

What blocks the activation of the kinase that phosphorylates glycogen phosphorylase?

Back 110

ATP

Front 111

What can further activate glycogen phosphorylase?

Back 111

AMP

Front 112

What can dephosphorylate the glycogen phosphorylase enzyme?

Back 112

phosphatase (this deactivates it)

Front 113

When glycogen phosphorylase is active what does it do?

Back 113

catalyzes the 1st step of glycogen breakdown

Front 114

A low bl. sugar leads to a rise in what?

Back 114

glucagon

Front 115

The active form of glycogen phosphorylase has ? ? sites.

Back 115

glucose receptor

Front 116

How does an increase in the conc. of insulin effect glycogen phosphorylase?

Back 116

causes it to move to a less active form

Front 117

Glycogen phosphorylase breaks down glycogen to yield what?

Back 117

glucose 1-phosphate

Front 118

glycogen phophorylase is activated by what?

Back 118

1. glucagon (liver)

2. Epinephring (muscle)

3. Ca2+, AMP (muscle)

Front 119

glycogen phophorylase is inactivated by what?

Back 119

1. glucose

2. insulin

Front 120

glycogen phophorylase activation is prevented by what?

Back 120

ATP (b/c if you have it in cells you don't need to breakdown more glucose)

Front 121

Which enzyme is involved in the regulation of glycogen SYNTHESIS?

Back 121

glycogen synthase

Front 122

The active form of glycogen synthase?

Back 122

not phosphorylated

Front 123

The inactive form of glycogen synthase?

Back 123

phosphorylated

Front 124

What inactivates glycogen synthase?

Back 124

many protein kinases BUT the most important is glycogen synthase kinase 3 (GSK 3)

Front 125

GSK 3 is becoming a popular what?

Back 125

drug target

Front 126

What does GSK 3 do?

Back 126

converts active glycogen synthase to inactive form

Front 127

What is the key mediator in the regulation of glycogen synthase?

Back 127

insulin...inactivates glycogen synthase by blocking GSK 3

Front 128

What activates glycogen synthase?

Back 128

PP1 (phosphoprotein phosphatase)

Front 129

3 things that activate PP1 and lead to the activation of glycogen synthase?

Back 129

1. insulin

2. glucose 6-phosphate

3. glucose

Front 130

2 things that inactivates PP1 thus inactivating glycogen synthase?

Back 130

glucagon and epinephrine

Front 131

What inactivates GSK 3 thus blocking the inactivation of glycogen synthase?

Back 131

insulin

Front 132

What 4 things lead to glycogen synthase being more active?

Back 132

1. PP1 activation by glucose

2. PP1 activation by glu 6-phosphate

3. PP1 activation by insulin

4. GSK 3 inactivation by insulin

Front 133

2 things that lead to a less active form of glycogen synthase?

Back 133

2. PP1 blocked by glucagon

2. PP1 blocked by epinephrine

Front 134

5 general factors that affect the response to immunogens?

Back 134

1. amt of immunogen

2. route of exposure

3. genotype of recipient

4. repetition

5. adjuvant

Front 135

How does the amt of immunogen affect the response to immunogens?

Back 135

In excessively large doses it can lead to intolerance and too little will not elicit a response.

Front 136

Give an example of how the route of exposure affect the response to immunogens?

Back 136

oral exposure evokes a different response than parenteral exposure (all types of exposures give an unique response)

Front 137

List 4 different routes of exposure?

Back 137

1. IV (goes to spleen)

2. IM (goes to lymph nodes)

3. SC (goes to lymph nodes)

4. oral route (goes to gut mucosa)

Front 138

How does the genotype of the recipient affect the response to immunogens?

Back 138

The recipients type of MHC, B-cell and T-cell genes will influence the degree of reactivity or if you will have no reaction.

Front 139

Explain how repetition affects the response to immunogen?

Back 139

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.

Front 140

How do adjuvants affect the response to immunogens?

Back 140

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.

Front 141

The only adjuvant approved by the FDA for use?

Back 141

alum

Front 142

4 effects of adjuvant?

Back 142

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

Front 143

2 examples of Adjuvants?

Back 143

1. alum

2. freund's adjuvant

Front 144

4 points about alum?

Back 144

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

Front 145

What is a granuloma?

Back 145

Occur when macrophages flow to the area of an adjuvant and form a cluster. A rich mass of cells with a "lumpy" appearance.

Front 146

What is the typical adjuvant used in the lab?

Back 146

Freund's adjuvant

Front 147

Why are adjuvants used in studies?

Back 147

They are used because they make immunological studies appear more effective than they actually are.

Front 148

Epitopes are ? determinants.

Back 148

antigenic

Front 149

What do large molecules do?

Back 149

They induce an immune response.

Front 150

What is an epitope?

Back 150

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.

Front 151

An Ag may contain several distinct ?.

Back 151

epitopes

Front 152

Ab or TCR will target how many epitopes?

Back 152

EACH one will only target one epitope.

Front 153

What is the percentage of the total surface area of a protein is taken up by ONE epitope?

Back 153

10%

Front 154

Why must Epitopes and Abs have complementary shapes?

Back 154

For short-range binding forces (van der waals)

Front 155

Where are epitopes developed?

Back 155

In the marrow for B-cells and in the thymus for T-cells.