PPP and glycogen Metabolism

Question 1

The pentose phosphate pathway (PPP)

Answer 1

an interchange of metabolic pathways. The pathway doesn’t really have a beginning or an end and the direction it moves depends on what is available and what the cell needs. Molecules in the highest concentration will serve as input sources for the pathway and molecules in the least abundance will serve as outputs of the pathway.

Question 2

importance to the cell?

Answer 2

a) an important source of NADPH, b) an important source of ribose-5-phosphate for nucleotide synthesis; c) an interchange; and d) a way to mix and match sugars according to the needs of cells.

Question 3

Carbon rearrangements are catalyzed by

Answer 3

transaldolase (one carbon swaps) and transketolase (two carbon swaps).

Question 4

Transketolase requires

Answer 4

thiamine pyrophosphate (from the vitamin thiamine) as a coenzyme.

Question 5

structure of glycogen

Answer 5

consists of units of glucose linked in the alpha 1-4 configuration with branches linked in the 1-6 configuration. (much more branching than starch)

Question 6

Glycogen

Answer 6

a storage form of energy that can yield ATP very quickly, because glucose-1-phosphate can be released very quickly.

Question 7

function/activites of the enzymes in glycogen breakdown

Answer 7

glycogen phosphorylase, phosphoglucomutase, and debranching enzyme.

Question 8

Glycogen phosphorylase

Answer 8

action on glycogen yields glucose-1-phosphate. Glycogen phosphorylase exists in two forms - phosphorylase a and phosphorylase b. Phosphorylase a differs from phosphorylase b only in that phosphorylase a contains two phosphates and phosphorylase b contains none. Phosphate is added to glycogen phosphorylase by the enzyme phosphorylase kinase.

Question 9

Glucose-6-phosphate (G6P)

Answer 9

breakdown of glycogen produces G1P, which is readily converted to G6P. G6P can then go three different directions. In muscle and brain (and most other tissues), G6P enters glycolysis. In liver only, G6P enters gluconeogenesis and is converted to glucose for export to the bloodstream. In other tissues, G6P enters the pentose phosphate pathway and is oxidized to produce NADPH.

Question 10

Phosphoglucomutase

Answer 10

interconverts G1P and G6P via a G1,6BP intermediate. The reaction is readily reversible (Delta G zero prime near zero) and the direction of the reaction depends on the concentration of substrates.

Question 11

Glycogen phosphorylase

Answer 11

catalyses phosphorolysis of glycogen to within 4 residues of a branch point and then stops. Further metabolism of glycogen requires action of Debranching Enzyme.

Question 12

Debranching enzyme

Answer 12

removes three of the remaining four glucoses at a branch point and transfers them to another chain in a 1-4 configuration. The remaining glucose in the 1-6 configuration at the branch point is cleaved in a hydrolysis reaction to yield free glucose. It is the only free glucose released in glycogen metabolism.

Question 13

uridine diphosphate glucose (UDP-Glucose or UDPG) created by?

Answer 13

Synthesis of glycogen is not the simple reversal of the steps in glycogen breakdown. There is an energy barrier that must be overcome - synthesis of the alpha1,4 bond between adjacent glucoses in glycogen. This is accomplished by a ‘side-step’ reaction

Question 14

UDPG is an activated intermediate

Answer 14

a molecule with a high energy bond that uses the energy of that bond to donate a part of itself to something else.

Question 15

Regulation of glycogen phosphorylase is by two mechanisms

Answer 15

covalent modification and allosterism.

Question 16

Glycogen phosphorylase is present in two forms that differ in their phosphorylation

Answer 16

GPa (glycogen phosphorylase a) has phosphate and GPb (glycogen phosphorylase b) does not. GPb is converted into GPa by phosphorylation at two sites. Covalent modifications are DIFFERENT from allosteric controls, which interconvert the R and T states of BOTH GPa and GPb.

Question 17

GPb is inhibited by

Answer 17

ATP and G6P (converts R state to T state). When the body is at rest, ATP and G6P levels are high enough to turn GPb off. GPb is ONLY converted to the R state (activated) when AMP is present in sufficiently high concentrations.

Question 18

in normally resting cells

Answer 18

GPa is usually in the R state (active) and GPb is usually in the T state (inactive). Thus, processes like phosphorylation/dephosphorylation which interconvert GPa and GPb have major effects on whether or not glycogen breakdown is occuring.

Question 19

The enzyme responsible for phosphorylating glycogen phosphorylase

Answer 19

is known as (glycogen) phosphorylase kinase. This interesting enzyme is activated by two different mechanisms - phosphorylation and/or calcium ions.

Question 20

Calcium ions

Answer 20

bind to phosphorylase kinase by virtue of the fact that the protein calmodulin (which binds calcium ions) is a subunit of phosphorylase kinase.

Question 21

Calcium alone only partly activates phosphorylase kinase. Full activation of phosphorylase kinase requires

Answer 21

he protein be phosphorylated as well. Phosphorylation of phosphorylase kinase is catalyzed by protein kinase A. Phosphorylation of phosphorylase kinase alone can also partly activate phosphorylase kinase, just as was the case with calcium. Either binding of calcium ion or phosphorylation can happen first. There is no required order to the binding.

Question 22

In the cascade system initiated by binding of epinephrine or glucagon to a cell-surface receptor, turning off the system involves

Answer 22

a) inactivating the 7TM (discussed earlier in the term); b) inactivation of the G-protein (GTPase), c) breakdown of cAMP (phosphodiesterase); and d) reversal of the protein phosphorylations. The last step requires phosphoprotein phosphatase and that enzyme is activated by binding of insulin to the cell surface receptor.

Question 23

Ephiephrine/glucagon favors

Answer 23

phosphorylation of glycogen enzymes, which activates glycogen breakdown and inactivates glycogen synthesis - makes sense when glucose is lacking.

Question 24

Insulin favors

Answer 24

dephosphorylation, which activates glycogen synthesis and inactivates glycogen breakdown.