PPP and glycogen Metabolism Flashcards
The pentose phosphate pathway (PPP)
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.
importance to the cell?
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.
Carbon rearrangements are catalyzed by
transaldolase (one carbon swaps) and transketolase (two carbon swaps).
Transketolase requires
thiamine pyrophosphate (from the vitamin thiamine) as a coenzyme.
structure of glycogen
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)
Glycogen
a storage form of energy that can yield ATP very quickly, because glucose-1-phosphate can be released very quickly.
function/activites of the enzymes in glycogen breakdown
glycogen phosphorylase, phosphoglucomutase, and debranching enzyme.
Glycogen phosphorylase
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.
Glucose-6-phosphate (G6P)
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.
Phosphoglucomutase
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.
Glycogen phosphorylase
catalyses phosphorolysis of glycogen to within 4 residues of a branch point and then stops. Further metabolism of glycogen requires action of Debranching Enzyme.
Debranching enzyme
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.
uridine diphosphate glucose (UDP-Glucose or UDPG) created by?
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
UDPG is an activated intermediate
a molecule with a high energy bond that uses the energy of that bond to donate a part of itself to something else.
Regulation of glycogen phosphorylase is by two mechanisms
covalent modification and allosterism.
Glycogen phosphorylase is present in two forms that differ in their phosphorylation
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.
GPb is inhibited by
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.
in normally resting cells
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.
The enzyme responsible for phosphorylating glycogen phosphorylase
is known as (glycogen) phosphorylase kinase. This interesting enzyme is activated by two different mechanisms - phosphorylation and/or calcium ions.
Calcium ions
bind to phosphorylase kinase by virtue of the fact that the protein calmodulin (which binds calcium ions) is a subunit of phosphorylase kinase.
Calcium alone only partly activates phosphorylase kinase. Full activation of phosphorylase kinase requires
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.
In the cascade system initiated by binding of epinephrine or glucagon to a cell-surface receptor, turning off the system involves
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.
Ephiephrine/glucagon favors
phosphorylation of glycogen enzymes, which activates glycogen breakdown and inactivates glycogen synthesis - makes sense when glucose is lacking.
Insulin favors
dephosphorylation, which activates glycogen synthesis and inactivates glycogen breakdown.
