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Glycogen metabolism

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glucose is a six

carbon molecule that's used to make

energy in the form of adenosine triphosphate

triphosphate

or atp glucose is such an important

energy source that our body stores

excess glucose in skeletal muscle cells

and liver cells in the form of glycogen

glycogen is basically an enormous

molecule or polymer

that's made up of glucose molecules

linked together by glycosidic bonds

you can think of glycogen having a main

chain and there being multiple branches

sprouting off of it

these branches allow glycogen to be

compact and capable of rapid addition

it's kind of like growing a plum tree in

a tiny house with a short ceiling

the short ceiling limits the tree's

vertical growth but the tree is able to

branch off

so that it can still grow and produce

many plums into tight space

now let's say that you just wrapped up a

delicious lunch you had tacos

glucose is absorbed from the intestine

and that causes our blood sugar to go up

the pancreas responds to high blood

sugar by secreting insulin

insulin axon glucose transporters on the

cell membrane

which are called glutes and makes them

bring more glucose into all cells in our body

inside the cell an enzyme called

hexokinase adds a phosphate group to its

sixth carbon

creating glucose 6-phosphate then

glucose-6-phosphate is broken down

during glycolysis

making atp as a by-product over time atp

levels start to rise and that inhibits

certain enzymes in glycolysis

when that happens the extra glucose

6-phosphate can be used to make glycogen

that usually takes place in the liver

there are four main steps in glycogen synthesis

synthesis

first is attaching a uridine diphosphate

or udp molecule to glucose

second is attaching the glucose part of

the udp glucose molecule to a glycogen

primer called glycogenin

forming a short linear glycogen chain

which serves as a primer

third is adding more glucose molecules

to the primer

a bit like forming a conga line [Music]

[Music]

and fourth is adding branches to the

glycogen molecule

so starting with step one to make udp glucose

glucose

an enzyme called phosphoglucomutase

moves the phosphate from the sixth

carbon of glucose six phosphate to the

first carbon

creating glucose one which uniquely

comes in the form of uridine triphosphate

triphosphate

or utp in the presence of glucose

1-phosphate and utp

an enzyme called udp-glucose

pyrophosphorylase cuts

phosphate molecules off of utp which

give the energy necessary to complete

this reaction

so only one phosphate remains attached

to uridine

and then glucose one phosphate is added

to it

that makes two phosphates so the

resulting molecule is called udp glucose

once many glucose molecules are

converted into udp glucose molecules

we're ready to create glycogen an enzyme

called glycogen synthase

catalyzes the attachment of the glucose

part of udp glucose to another glucose

residue at the end of the glycogen branch

branch

forming an alpha 1 4 glycosidic bond

it's almost as if the glucose molecules

are holding hands

and in addition to prolonging the

glycogen chain another byproduct of this

reaction is udp

but it turns out that glycogen synthase

can only elongate an already existing

glycogen chain that's at least four

glucose molecules long

so if there aren't at least four glucose

molecules linked up together already

then glycogen synthesis requires a

protein called glycogenin

glycogenin plays the role of fooling

glycogen synthase by catalyzing the

attachment of four glucoses to itself

creating a short chain connected with

alpha one four glycosidic bonds

by doing that it's able to tell glycogen

synthase hey we have a chain here that

looks kind of like an old glycogen molecule

molecule

and elongates this short chain on

glycogenin by attaching lots of glucose

molecules to it through alpha-1-4

glycosidic bonds

this elongates the chain and creates a

next an enzyme called the branching

enzyme goes to the end of the chain and

cuts off a chain of about six to eight

glucose residues in length

the branching enzyme then attaches that

chain to the side of the linear glycogen

strand by creating an alpha 1

6 glycosidic bond so there's now a bond

between the first carbon of the glucose

on the small cleaved segment

and the sixth carbon of a glucose that's

part of the linear chain

and as soon as you've shortened the

linear chain glycogen synthase will

this happens over and over again

resulting in a branched glycogen tree to

serve as stored energy

now let's say it's been a couple of

hours since those tacos

and you decide to go for a run because

you're fasting your blood glucose levels

take a dip

in response the pancreas secretes the

hormone glucagon

and the adrenal glands secrete

epinephrine to increase your heart rate

it turns out that glucagon tells the

liver cells to break glycogen down into

individual glucose molecules

and epinephrine tells skeletal muscle

cells to do the same thing

in both the liver and skeletal muscle

cells glycogen breakdown starts with the branches

branches

first an enzyme called glycogen

phosphorylase cleaves the alpha 1

4 bonds between individual glucose

residues and catalyzes the transfer of a

phosphate group to the free

glucose the result is that the enzyme

releases one glucose one phosphate

molecule at a time

it keeps on doing this until exactly

four glucose molecules were made on the branch

branch

next a de-branching enzyme literally

cuts off glycogen branches

it has a component called four alpha glucanotransferase

glucanotransferase

which transfers three out of the four

glucose molecules off of the branch and

reattaches them to the linear glycogen

chain instead

extending it as a result the same

debranching enzyme has another component

known as alpha 1-6

glucosidase which cleaves off the

alpha-1-6 glycosidic bond and releases a

so for each glucose that's removed via phosphorylysis

phosphorylysis

there's a glucose 1-phosphate that gets

liberated and it's converted to

glucose-6-phosphate by phospho-glucomutase

phospho-glucomutase

the difference between glycogen

breakdown in the liver and what goes on

in the muscles

results from different enzymes in those

two tissues

in liver cells glucose 6-phosphatase

removes the phosphate off of the sixth carbon

carbon

releasing free glucose into the

bloodstream for other organs and tissues

to use

skeletal muscle doesn't have this enzyme

so it simply uses the glucose

6-phosphate by sending it into the

glycolysis pathway to make energy

that can help you with that run

glycogen metabolism is primarily

regulated by two pancreatic hormones

insulin and glucagon now a general rule

of thumb

is that glycogen synthase is active when

it doesn't have a phosphate

whereas glycogen phosphorylase is active

when it does have a phosphate attached

to it

so in liver and skeletal muscle cells

insulin binds to a tyrosine kinase

receptor on the cell surface

and that ultimately activates a protein

phosphatase which goes around removing

phosphates from glycogen synthase

making it active as well as from

glycogen phosphorylase

making it inactive this promotes

glycogen synthesis

and decreases its breakdown

on the other hand glucagon in the liver

cells bind to a g-protein-coupled

receptor on the cell surface

which activates adenolyl cyclase which

converts atp to cyclic amp

or camp camp then activates protein

kinase a

which adds a phosphate to glycogen

phosphorylase kinase

which activates it glycogen

phosphorylase kinase adds a phosphate to

glycogen phosphorylase

increasing its activity and promoting

glycogen breakdown

it also adds a phosphate glycogen

synthase decreasing its activity and

therefore decreasing glycogen synthesis

all right as a quick recap glycogen is a

multi-branched compact structure that's

made of alpha-1-4 glycosidic bonds

between the glucose molecules

and alpha-1-6 bonds at the branching points

points

glycogen is considered the major form of

glucose storage in the body

and it's primarily stored in the liver

cells and skeletal muscle cells

after a meal high insulin levels promote

glycogen synthesis

whereas during fasting high glucagon and

epinephrine levels promote glycogen breakdown

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