Glycogen, TCA Cycle and Mitochondria (Lecture 6)

Question 1

when do glycogen levels increase?

Answer 1

after meals

Question 2

when is glycogen used?

Answer 2

during fasting and exercise

Question 3

why is glycogen stored?

Answer 3

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

Question 4

hw is glycogen used in the muscle?

Answer 4

used foo local energy contraction to produce energy for muscle contraction

Question 5

why cant the muscle release glucose into the blood?

Answer 5

muscle does not contain G6P phosphatase, thus the glucose produced in the muscle via glycogen breakdown is sequestered in the muscle

Question 6

explain the process of glycogen break down in the liver…

Answer 6

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.

Question 7

why/where is G6P compartmentalized?

Answer 7

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

Question 8

reducing end

Answer 8

contain an OH on C1

only one per molecule

Question 9

glycosyl residues are linked by…

Answer 9

C1-C4 alpha linkage

Question 10

branching points are linked by

Answer 10

C1-C6 alpha linkages

Question 11

what is the benefit of branching?

Answer 11

provides a larger number of ends to allow multiple sites for synthesis and degradation

Question 12

glucose molecules are added/chopped off from

Answer 12

the non reducing ends

Question 13

what is the rate limiting enzyme for glycogen degradation?

Answer 13

glycogen phosphorylase

Question 14

what is the rate limiting enzyme for glycogen synthesis?

Answer 14

glycogen synthase

Question 15

third step of glycogen synthesis

Answer 15

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

Question 16

what is the activated form of glucose?

Answer 16

UDP glucose

Question 17

why is the hydrolysis of UTP important for glycogen synthesis ?

Answer 17

UTP hydrolysis gives energy to make the high energy intermediate, UDP glucose

Question 18

first step of glycogen synthesis?

Answer 18

when glucose enters the cell, ATP is invested to make G6P via a hexokinase

Question 19

what is the second step of glycogen synthesis?

Answer 19

G6P is converted into G1P via phosphoglucomutase

Question 20

what is the forth step of glycogen synthesis?

Answer 20

elongation of pre-existing glycogen chain with UDP glucose

this is done with the rate limiting enzyme glycogen synthase

this releases UDP

Question 21

what is the fifth step in glycogen synthesis?

Answer 21

creation of new 1,6 glucose branch points Bia branching enzyme

Question 22

the synthesis of UDP glucose is ____

Answer 22

irreversible

Question 23

how is the build up of UDP resolved to allow glycogen synths to continue?

Answer 23

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

Question 24

what enzyme is used to restore UDP?

Answer 24

nucleoside diphosphate kinase

Question 25

what does glycogenin do?

Answer 25

primes glucose for the synthesis of are glycogen molecules

Question 26

where is glucose bound to on glycogenin and what occurs at this location?

Answer 26

tyrosine 194 residue where it will glycosylate the glucose to make an 8 glucose primer

Question 27

what is the mechanism for glycogen synthesis de novo?

Answer 27

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

Question 28

glycogen synthase is only efficient when…

Answer 28

bound to glycogenin

Question 29

what is the link between glycogen and glycogenin

Answer 29

the number of glycogenin = the number of glycogen

Question 30

when does glycogen elongation stop?

Answer 30

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

Question 31

what does the branching enzyme do?

Answer 31

add new 1,6 glycosyl branch points

Question 32

what are the rules of glycogen synthesis?

Answer 32

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

Question 33

what are the three domains of glycogen synthase and their functions?

Answer 33

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

Question 34

the synthesis of glycogen from glucose costs:

Answer 34

2 ATP per residue

these investments orifginate from the steps:

glucose +ATP to G6P

G1P +UTP to UDP glucose

Question 35

what are the general steps in glycogen breakdown?

Answer 35

generation of G1P

debranching

conversion of G1P to G6P

Question 36

explain how we break down branched glycogen?

Answer 36

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

Question 37

explain the reactions involved in the glycosidic bond breaking

Answer 37

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

Question 38

what occurs in the phosphorylase reaction?

Answer 38

glycogen phosphorylase will form glycogen (n-1) + G1P from glycogen AND Pi

Question 39

how is the phosphorylase reaction favourable?

Answer 39

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

Question 40

what is the function of alpha(1-4) glycosyltransferase?

Answer 40

transfers an alpha 1,4 linked trisaccharide to the non reducing end of another branch

the 3 units are then available for phosphorylase reaction

Question 41

what is the function of alpha(1-6) glucosidase?

Answer 41

the remaining glycosyl residue will be hydrolyzed to yield a glucose and a debranched glycogen

Question 42

what is the function of phosphoglucomutase? (2 steps)

Answer 42

convert G1P –> G6P

G1P to G1,6P by phsophoryalting the C6 OH

G16P –> G6P phoshphorylation of the enzyme via phosphorylation group at C1 position

Question 43

in the muscle G6P is used for:

Answer 43

continues into glycolysis to generate ATP

Question 44

in the liver G6P is:

Answer 44

converted to glucose and goes into circulation

Question 45

glycogen breakdown generates:

Answer 45

33 ATP/ glucose

glycogen breakdown generates G6P (no need for hexokinase) an already phosphorylated compound, thus no ATP needed