Chapter 15

Question 1

Cells & organisms maintain a ____________ steady state

Answer 1

Dynamic

Question 2

Flux

Answer 2

Is the rate of one metabolite flow in metabolism

Question 3

Flux through pathways must be regulated to do what?

Answer 3

1. Achieve the physiological function of a tissue
2. Maintain homeostasis
3. Adapt too changing needs (such as development, nutrient intake, activity level, etc)

Question 4

Flux depends on what?

Answer 4

1. Amount of enzyme present
2. The activity of the enzyme

Question 5

Enzymes of _____________ steps are key regulatory enzymes that play a role in flux

Answer 5

irreversible

Question 6

Both the amount & __________ activity of an enzyme can be regulated

Answer 6

Catalytic

Question 7

The total activity of an enzyme can be changed by altering the number of its __________ in the cell or its effective activity in subcellular compartments or by modulating the activity of existing molecules

Answer 7

molecules

Question 8

The different forms (isozymes) of hexokinase have different ____ values & are therefore affected differently by changes in glucose concentration

Answer 8

Km

Question 9

Km = [S] that gives 1/2Vmax so if [S] increases then the reaction rate ________________ to help maintain homeostasis

Answer 9

Increase

Question 10

ATP breaks down forming what?

Answer 10

ATP then AMP

Question 11

When ATP is low AMP is ______ & vis versa

Answer 11

High

Question 12

______ is used to regulate the body since small changes in its concentration results in a large relatvie change

Answer 12

AMP

Question 13

______ isn’t used at all in body regulation since its in the middle & no relative change is shown

Answer 13

ADP

Question 14

______ acts directly as an allosteric effector & also via phosphorylation of enzymes mostly by AMPK (AMP-activated protein kinase)

Answer 14

AMP

Question 15

_______ is activated by elevated [AMP] or decreased [ATP] & when activated AMPK phosphorylates target proteins & shifts metabolism in a variety of tissues away from energy-consuming process

Answer 15

AMPK

Question 16

Gluconeogenesis occurs mostly in the liver where its role is to regulate blood ______________

Answer 16

glucose levels

Question 17

Isozymes

Answer 17

Are different proteins that catlayze the same reaction but have different genes

Question 18

In muscle cells hexokinase I role is to convert glucose to glucose 6 phosphate at 0.1mM to provide _______ & when the concentration of glucose 6 phosphate is above that number, hexokinase I is temporarily inhibited to bring the concentration down

Answer 18

energy

Question 19

In the liver hexokinase IV converts glucose to ________________ (& then to fructose 6 phosphate) when blood glucose is high (Like after a meal)

Answer 19

glucose 6 phosphate

Question 20

The enzyme ______ has two binding sites (one where ATP binds & the other where AMPK binds) when [ATP] is high it signals that ATP is being produced faster than its being consumed so therefore ATP will inhibit PFK-1 by binding to an allosteric site which inhibits the binding for ATP as its substrate

Answer 20

PFK-1

Question 21

________ (used for aerobic oxidation of pyruvate, etc) is also an allosteric regulator of PFK-1 so high [citrate] also inhibits ATP binding which further reduces the flow of glucose through glycolysis

Answer 21

Citrate

Question 22

When [ATP] is _______& [AMP] is high it will bind to the allosteric subunit, therefore, releasing ATP in PFK-1 & stimulating the ATP binding site

Answer 22

low

Question 23

The regulation of fructose 6 phosphates (for gluconeogenesis) or fructose 1,6 bisphosphate (for glycolysis) is regulated by ________ & ________ where high [ADP] & [AMP] stimulates glycolysis (high [ATP] & [Citrate] inhibits PFK-1 for glycolysis)

Answer 23

PFK-1 & FBPase-1

Question 24

The 3 key enzymes for regulating glycolysis are what?

Answer 24

The enzymes at the3 irreversible steps

Question 25

How does the liver regulate blood glucose?

Answer 25

With hexokinase IV & a regulatory protein, when [glucose] is high its insides the liver cytosol & when [Fructose 6 phosphate] is high its moved outside to the nucleus

Question 26

The reaction of Fructose 6 phosphate to fructose 1,6 phosphate is inhibited by _________ & ________ & stimulated by AMP, ADP, & fructose 2,6 bisphosphate

Answer 26

ATP & Citrate

Question 27

The regulation of glycolysis & gluconeogenesis is mediated (controlled) by _________________

Answer 27

Fructose 2, 6 bisphosphate

Question 28

Glucose can be stored as __________

Answer 28

Glycogen

Question 29

_________ is a branched polymer of alpha (1—>4) linked glucose with alpha (1—>6) linkage every 12 to 14 glucose units

Answer 29

Glycogen

Question 30

Glycogen storage occurs mainly in the ___________ & Muscle

Answer 30

Liver

Question 31

Glycogen is degraded to ____________ units for use in energy production

Answer 31

glucose

Question 32

_____________ can be made from excess blood glucose or recycling of gluconeogenic metabolites like lactate or certain amino acids

Answer 32

Glycogen

Question 33

Glycogenolysis (degradation)

Answer 33

The break down of glycogen to glucose 1-phosphate

Question 34

Glycogenesis (synthesis)

Answer 34

The synthesis of glycogen

Question 35

Glycogen breakdown is catalyze by the enzyme glycogen phosphorylase & in which an alpha 1-4 glycosidic linkage between two glucose residues at a ______________ end of glycogen undergoes attack by inorganic phosphate & removing the terminal glucose residue as alpha D-glucose 1 phosphate

Answer 35

Non-reducing end

Question 36

_________________ (the end product of glycogen phosphorylase reaction) is converted to glucose 6 - phosphate by phosphoglucomutase (catalyzes a reversible reaction

Answer 36

Glucose 1 phosphate

Question 37

Glycogen synthesis mostly occurs in _________ & skeletal muscles

Answer 37

Liver

Question 38

The starting point of glycogen is _________________________ which is converted to glucose 1 - phosphate with the enzymes phosphoglucomutase where glucose 1phosphate is then converted into UDP-glucose by the enzymes UDP-glucose pyrophosphorylase

Answer 38

glucose 6 phosphate

Question 39

The sugar nucleotide __________ donates glucose for glycogen synthesis

Answer 39

UDP- glucose

Question 40

Sugar nucleotides

Answer 40

Compounds in which the anomeric carbon of sugar is activated by the attachment to a nucleotide through a phosphate ester linkage

Question 41

Glycogen synthase can’t make the ______________ bonds found at the branch points of glycogen

Answer 41

alpha 1-6

Question 42

____________________ is regulated by hormone-triggered covalent modification & allosteric effects

Answer 42

Glycogen phosphorylase

Question 43

Glycogen phosphorylase is regulated in what 3 ways?

Answer 43

1. Activated by phosphorylation
2. Allosteric activation by AMP
3. De-activation when glucose returns to normal (combination of allosteric effects & covalent modification)

Question 44

What are the main hormonal signals?

Answer 44

1. Insulin
2. Glucagon
3. epinephrine

Question 45

Insulin _____________ glycogen degradation & increase synthesis in the liver

Answer 45

Decrease

Question 46

Glucagon increases glycogen degradation & __________ glycogen synthesis in the liver

Answer 46

Decrease

Question 47

epinephrine _____________ glycogen degradation & decrease glycogen synthesis in the liver & muscle

Answer 47

increase

Question 48

The enzyme ______________ is responsible for activating phosphorylase by transferring a phosphoryl group to its Ser residue & is activated by epinephrine or glucagon (this is the activation of phosphorylation)

Answer 48

phosphorylase b kinase

Question 49

______ the signal for muscle contraction binds to & activates phosphorylase b kinase promoting the conversion of phosphorylase b to active a form

Answer 49

Ca2+

Question 50

When muscle returns to rest the enzyme ____________________ removes the phosphoryl groups form phosphorylase a converting it to the less active form b

Answer 50

phosphoprotein phosphate 1 (PP1)

Question 51

Glycogen synthesis is also regulated by ______________________________

Answer 51

phosphorylation & dephosphorylation

Question 52

Describe the regulation of muscle glycogen phosphorylase by covalent modification.

Answer 52

In the more active form of the enzyme, phosphorylase a, Ser14 residues. one on each subunit, are phosphorylated. Phosphorylase a is converted to the less active form, phosphorylase b, by enzymatic loss of these phosphoryl groups, catalyzed by phosphoprotein phosphatase 1 (PP1). Phosphorylase b can be reconverted (reactivated) to phosphorylase a by the action of phosphorylase b kinase. (See also Fig. 6-43 on glycogen phosphorylase regulation.)

Question 53

Describe the effects of GSK3 on glycogen synthase activity.

Answer 53

Glycogen synthase a, the active form, has three Ser residues near its carboxyl terminus, which are phosphorylated by glycogen synthase Kinase 3 (GSK3). This converts glycogen synthase to the inactive (5) form. GSK3 action requires prior phosphorylation (priming) by casem Kinase (CKII). Insulin triggers activation of glycogen synthase b by blocking the activity of GSK3 (see the pathway for this action in Fig. 12-20) and activating phosphoprotein phosphatase 1 (PP1).

Question 54

Describe glycogen phosphorylase of the liver as a glucose sensor.

Answer 54

Glucose binding to an allosteric site of the phosphorylase a isozyme of liver induces a conformational change that exposes its phosphorylated Ser residues to the action of phosphoprotein phosphatase 1 (PP1). This phosphatase converts phosphorylase a to phosphorylase b, sharply reducing the activity of phosphorylase and slowing glycogen breakdown in response to high blood glucose. Insulin also acts indirectly to stimulate PP1 and slow glycogen breakdown.