lecture 15 glycogen metabolism and pentose pathways

carbohydrate storage, liver, muscle

glucose polymer, glycogen, serves as the major form of ___ in the ____ and ___ of humans

glycogen structure

backbone of α-1,4 linked glucose units with α-1,6 branches occurring about every 10-12 glucose units

liver and muscle

largest glycogen stores are found in

glycogen polymer

contains about 90% 1-4-linked glucose units and 10% 1-6-linked glucose units.

extensive branching (provides non reducing ends)

what makes glycogen subject to enzymatic hydrolysis reactions

1

how many reducing ends are there where a glucose unit could undergo mutarotation to the open chain form.

enzyme phosphorylase, glycogen, product

_____ attacks the non-reducing ends of ___, releasing 1,4-linked glucose units as glucose-1-P. This reaction proceeds in the direction of ____ formation.

transferase enzyme

____ and an α-1,6-glucosidase enzyme convert the 1,6-branches into additional linear 1,4-linked glucose units. That transformation allows phosphorylase a action to continue further into the glycogen molecule.

glucose-6-P , phosphoglucomutase, glycolysis

The glucose-1-P units produced by phosphorylase a are converted to____ by the enzyme _____. The glucose 6-P can then enter into the ____pathway.

glycogen, glucose, anabolic

___ can be synthesized from ___ using different ____enzymes than those used for glycogen breakdown.

synthesis of glycogen

reversal of glycogen breakdown is

releasing

The cleavage of glycogen is an energy ____ reaction, so energy input is necessary to make the reverse reaction proceed.

glycogen synthesis

employs a set of enzymes to reverse the action of phosphorylase a.

activated (UDP-glucose) sugar nucleotide

Glycogen synthesis proceeds through an ____ intermediate.

glycogen synthesis step 1

catalyzed by UDP-glucose pyrophosphorylase. In that reaction, glucose-1-P reacts with UTP to form UDP-glucose and release an inorganic pyrophosphate (PPi).

pyrophosphate (PPi), releasing, product

The ____ released in the previous reaction can be hydrolyzed to form two Pi's. The hydrolysis of PPi is an energy ____process that removes the product of the previous reaction and helps to drive the overall reaction sequence toward
____formation.

glycogen synthesis step 2

synthase enzyme transfers a glucose unit from UDP-glucose to the non-reducing end of glycogen. UDP is released as the other product

alternate enzyme

use of ____ systems allows both systems to be subject to hormonal regulation

simultaneously

The net result of hormonal regulation is that both systems do not function _____

hormones

organic compounds that are synthesized in one tissue and are transported through the blood to another tissue, where they exert an effect of metabolic processes.

adrenaline

low molecular weight hormone that is derived from an amino acid

epinephrine

stimulates a series of reactions that result in the activation of the catabolic enzyme phosphorylase a, which degrades glycogen

regulatory cascade

The binding of a hormone to activate an extracellular receptor protein

regulatory cascade

The activation of a G protein by interaction with an activated extracellular receptor

regulatory cascade

The activation of adenylate cyclase by interaction with a G protein

regulatory cascade

The conversion of ATP to Cyclic AMP by the adenylate cyclase enzyme

regulatory cascade

The activation of a protein kinase enzyme by cyclic AMP -The activation of phosphorylase kinase by a phosphorylation reaction catalyzed by the cyclic AMP sensitive kinase -The conversion of phosphorylase b to phosphorylase a through phosphorylation by the phosphorylase kinase

regulatory cascade

The cleavage of glycogen by phosphorylase a

epinephrine

stimulates an enzyme cascade that results in the inactivation of the anabolic enzyme, glycogen synthase, which adds glucose units to glycogen.

dual function of epinephrine cascade

activating glycogen breakdown and simultaneously inactivating glycogen synthesis, prevents these reactions from catalyzing a futile cycle in which energy is wasted.

Adenylate cyclase

____ converts ATP to the second messenger, cyclic AMP. Second messengers are intracellular signaling agents that are often synthesized or degraded in response to the action of an extracellular hormone.

irreversible

adenylate cyclase reaction is essentially ____ because one of the products, inorganic pyrophosphate, is rapidly degraded by a pyrophosphatase enzyme. This strategy (the breakdown of inorganic pyrophosphate) is used often in biochemical pathways to force a reaction to go in the direction of product formation.

pentose phosphate, glycolysis, pentose sugars.

The ____ pathway is an alternate pathway to ___ that provides a source of NADPH for use in reductive biosynthesis. This pathway also generates_____

cytosol

All the reactions of the pentose phosphate pathway take place in the

reductive (That is, the products of biosynthesis are generally more reduced (have a higher % of hydrogen atoms) than the starting materials. )

Most anabolic (biosynthetic) pathways are __

NADPH

The reducing power for anabolic pathways comes from

Fatty acid, nucleotide

____ biosynthesis and ___ biosynthesis are examples of anabolic pathways that utilize NADPH.

pentose phosphate pathway step 1

runs from glucose 6-P to ribose 5-P, involves the oxidative generation of NADPH. -

pentose phosphate pathways step 2

involves the non-oxidative conversion of five-carbon sugars to intermediates of the TCA cycle, such as fructose 6-P, glyceraldehydes 3-P, and pyruvate.

oxidative phase, oxidized, reduced to NADPH,

In the ___, the starting material, glucose 6-P, is ___ to ribulose 5-P. In two of the reactions, the cofactor NADP+ is ____. In fact, all of the NADPH produced by the pentose phosphate pathway is synthesized in the oxidative phase.

net reaction of the oxidative phase

glucose 6-phosphate + 2 NADP+ + H20
ribulose 5-phosphate + 2 NADPH + 2 H+ + C02

non oxidative phase

the five carbon sugars xylulose 5-P and ribose-5 P are converted to fructose 6-P and glyceraldehyde 3-P.

non oxidative phase

The products of this phase are mainstream metabolites that can enter glycolysis or gluconeogenesis.

step 1 oxidative phase

catalyzed by glucose 6- P dehydrogenase. In this reaction, glucose 6-P (in the hemiacetal form) is oxidized to 6-phosphoglucano-δ-lactone (a cyclic ester), coupled to the reduction of NADP+ to NADPH.

step 2 oxidative phase

catalyzed by lactonase, is a ring opening that converts the lactone to the open chain carboxylic acid, 6-P-gluconate.

step 3 oxidative phase

the 6-P-gluconate is decarboxylated and oxidized to ribulose 5-P. The reaction is coupled to the reduction of a second molecule of NADP+ to NADPH.

step 4 oxidative

ribulose 5-P is first converted into two different five carbon compounds, ribose 5-P and xylulose 5-P, by two separate enzymes. These two five carbon intermediates are then converted to glyceraldehyde 3-P and fructose 6-P by a series of three reactions.

oxidative step 5

the ketone, ribulose 5-P, can be isomerized to the aldehyde, ribose 5-P. The reaction involves the formation of an unstable endiol intermediate, in which two adjacent carbon-atom-carrying hydroxyl groups are connected by a double bond. The endiol decays into an aldehyde, which is stable. This reaction completes the oxidative phase of the pathway.

oxidative step 6

isomerase reaction goes through an enediol intermediate

oxidative end

products are two molecules of NADPH, one molecule of carbon dioxide, and one molecule of ribose 5-phosphate.

non oxidative step 1

ribose 5-P is converted into xylulose 5-P by an epimerase reaction. This reaction simply changes the chirality of the hydroxyl group at the number three carbon, converting ribulose 5-P to xylulose 5-P.

non oxidative step 2 - transketolase

transketolase reaction, a two carbon fragment (coded in red) is transferred from xylulose 5-phosphate to ribose 5-phosphate. The products of this reaction are glyceraldehyde-3-phosphate and sedoheptulose 7-phosphate. The reaction is reversible, and under some modes of the pentose phosphate pathway, it will actually function in the reverse direction.

non oxidative step 3

two products of the previous reaction-- sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. The transaldolase enzyme transfers a three carbon fragment (coded in red) from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate, producing erythrose 4-phosphate and fructose 6-phosphate. In this step, one C-7 and one C-3 compound are converted into one C-4 and one C-6 compound.

non oxidative step 4 end

erythrose 4-phosphate product of the previous step reacts with a second xylulose 5- phosphate (from the phosphopentose epimerase reaction) to give glyceraldehyde-3-phosphate and fructose 6-phosphate. This reaction is catalyzed by the same transketolase enzyme we talked about before, but one of the substrates (erythrose 4-phosphate) and one of the products (fructose 6-phosphate) are different.