Glycogen, TCA Cycle and Mitochondria (Lecture 6) Flashcards
when do glycogen levels increase?
after meals
when is glycogen used?
during fasting and exercise
why is glycogen stored?
glycogen catabolism is faster than FA catabolism
can be used under anaerobic conditions
glycogen doesn’t disturb the osmotic pressure as an equivalent amount of glucose would
glycogen breakdown also provides G1P faster than glucose when taken cup by food
livers capacity to store glycogen is sufficient to supply the brain with glucose for up tp 12h
hw is glycogen used in the muscle?
used foo local energy contraction to produce energy for muscle contraction
why cant the muscle release glucose into the blood?
muscle does not contain G6P phosphatase, thus the glucose produced in the muscle via glycogen breakdown is sequestered in the muscle
explain the process of glycogen break down in the liver…
G6P will enter the ER lumen via the G6P transporter (T1)
G6P interacts with the catalytic site of glucose-6-phosphatase in the ER lumen
the enzyme converts G6P into glucose and Pi
glucose exits the ER lumen via a glucose transporter, T2 and Pi exits the lumen via T3
once glucose is in the cytosol, it is transported into the blood via GLUT2.
why/where is G6P compartmentalized?
G6P is compartmentalized in the ER lumen in glycogen break down in the liver. This is because the catalytic site of G-6-phosphatase for G6P is levanted within the lumen
another reason for compartmentalization is to avoid competition, as for G6P is an intermediate for many reactions
reducing end
contain an OH on C1
only one per molecule
glycosyl residues are linked by…
C1-C4 alpha linkage
branching points are linked by
C1-C6 alpha linkages
what is the benefit of branching?
provides a larger number of ends to allow multiple sites for synthesis and degradation
glucose molecules are added/chopped off from
the non reducing ends
what is the rate limiting enzyme for glycogen degradation?
glycogen phosphorylase
what is the rate limiting enzyme for glycogen synthesis?
glycogen synthase
third step of glycogen synthesis
G1P –> UDP-glucose with the investment of UTP via UDP-glucose phosphorylase
this also generates PPi which is rapidly hydrolyzed in vivo, thus. making the levels of PPi very low in the cell (favourable reaction)
PPi–>2Pi
what is the activated form of glucose?
UDP glucose
why is the hydrolysis of UTP important for glycogen synthesis ?
UTP hydrolysis gives energy to make the high energy intermediate, UDP glucose
first step of glycogen synthesis?
when glucose enters the cell, ATP is invested to make G6P via a hexokinase
what is the second step of glycogen synthesis?
G6P is converted into G1P via phosphoglucomutase
what is the forth step of glycogen synthesis?
elongation of pre-existing glycogen chain with UDP glucose
this is done with the rate limiting enzyme glycogen synthase
this releases UDP
what is the fifth step in glycogen synthesis?
creation of new 1,6 glucose branch points Bia branching enzyme
the synthesis of UDP glucose is ____
irreversible
how is the build up of UDP resolved to allow glycogen synths to continue?
UDP + ATP –> UTP + ADP
this regenerates UTP to allow for more synthesis of UDP glucose
also this is the second investment of ATP, the first being the conversion of G6P–>G1P
what enzyme is used to restore UDP?
nucleoside diphosphate kinase
what does glycogenin do?
primes glucose for the synthesis of are glycogen molecules
where is glucose bound to on glycogenin and what occurs at this location?
tyrosine 194 residue where it will glycosylate the glucose to make an 8 glucose primer
what is the mechanism for glycogen synthesis de novo?
glycogenin attaches a glucose residue donated by UDPG to the OH group of Tyr 194
glycogenin then extends the glucose chain up to 7 additional UDDGP-donated glucose residues to form the glycogen primer
then glycogen synthase commence glycogen synthesis by extending the primer
glycogen synthase is only efficient when…
bound to glycogenin
what is the link between glycogen and glycogenin
the number of glycogenin = the number of glycogen
when does glycogen elongation stop?
elongation stops when glycogenin isn’t bound to glycogen synthase
it will also stop elongating once the growth has surpassed the size of the linker
what does the branching enzyme do?
add new 1,6 glycosyl branch points
what are the rules of glycogen synthesis?
transfer 7 glycosyl residues to the C6-OH
each transferred segment must come from a chain of at least 11 residues
the are branch point must be at least 4 residues away from a mother branch point
what are the three domains of glycogen synthase and their functions?
binds to glycogenin
linker region (variable in length… the larger the linker , the large the glycogen molecule length) this limits the size
catalytic domain, enzymatic activity which causes glycosylation, thus the addition of a glucose chain
the synthesis of glycogen from glucose costs:
2 ATP per residue
these investments orifginate from the steps:
glucose +ATP to G6P
G1P +UTP to UDP glucose
what are the general steps in glycogen breakdown?
generation of G1P
debranching
conversion of G1P to G6P
explain how we break down branched glycogen?
in order to break down branched glycogen, we remove and transfer the branch to the non-reducing end and hydrolysis the remaining glucose.
an alpha 1,4 glycosyl transferase will transfer a trisaccharide to the non reducing end
this creates a linear glycogen molecule that can undergo a phosphorylate reaction via glycogen phosphorylase to form G1P
the remaining glucose molecule on the branch will be available for hydrolysis via alpha-1,6 glucosidase
this results in a debranched glycogen molecule and a glucose
explain the reactions involved in the glycosidic bond breaking
hydrolysis:
addition of water to the glycosidic bond to separate the two molecules
phosphorolysis:
addition of phosphoric acid to glycosidic bond
this results in a phosphorylated glucose on C1, there is no need to invest energy to create this intermediate
what occurs in the phosphorylase reaction?
glycogen phosphorylase will form glycogen (n-1) + G1P from glycogen AND Pi
how is the phosphorylase reaction favourable?
although the delta Go is +3.1 (endergonic), there is a high level of Pi within the cell, which is a level higher than that of the product
this makes the reaction favourable and exergonic in vivo
recall Pi levels are high because they go from PPi to 2Pi via pyrophosphatase
what is the function of alpha(1-4) glycosyltransferase?
transfers an alpha 1,4 linked trisaccharide to the non reducing end of another branch
the 3 units are then available for phosphorylase reaction
what is the function of alpha(1-6) glucosidase?
the remaining glycosyl residue will be hydrolyzed to yield a glucose and a debranched glycogen
what is the function of phosphoglucomutase? (2 steps)
convert G1P –> G6P
G1P to G1,6P by phsophoryalting the C6 OH
G16P –> G6P phoshphorylation of the enzyme via phosphorylation group at C1 position
in the muscle G6P is used for:
continues into glycolysis to generate ATP
in the liver G6P is:
converted to glucose and goes into circulation
glycogen breakdown generates:
33 ATP/ glucose
glycogen breakdown generates G6P (no need for hexokinase) an already phosphorylated compound, thus no ATP needed
