Glycemic Responses and Glycogenesis

Question 1

high blood glucose concentration effect

Answer 1

glucose toxic to DNA, proteins
=> decrease protein function
high BGC and longer time glucose is allowerd to be above 4-5mM = glycation more likely to occur
however glycation still occurs at 5mM
–> brain and RBC needs it

HbA1C : measures how much glucose molecules bound to haemoglobin in blood
–> RBC lives 100 days / 3 months
checks how glycated Hb is/ or formed bonds with glucose = to check BGC.

Question 2

Post-prandial glucose disposal for subjects with glucose intolerance, insulin resistance and diabetes and the key hormones involved

Answer 2

post prandial (after eating)
–> BGC increases = insulin secreted
liver absorbs glucose

1. Intolerant
   = cannot reestablish/ return to fasting blood glucose conc = slightly hyperglycemic after 2 hour (end of test)
2. Diabetic
   = already hyperglycemic during fasting stage
   after 2 hours, still high BGC
   -> always exposed to high BGC, proteins are reacting with glucose = damaged

Question 3

insulin mechanism

Answer 3

insulin can either tell cells to uptake glucose
- either oxidise it = glycolysis
- turn it into fat = lipogenesis
- glycogenesis
- GLUT-4 in muscle/adipose tissue

Question 4

starch componets

Answer 4

a polymer of glucose
1. Amylose
–> linear, forms helices, difficult to penetrate and hydrolyse, produces flatulence
2. amylopectin
–> branched, easy hydrolysis / digestion

Question 5

Summarise the similarities and differences in glycogenesis in different tissues (liver vs muscle)

Answer 5

Similarities in Glycogenesis (Liver vs. Muscle):

In both the liver and muscle, requires 2 ATP molecules when adding to glycogen chain
G–>G6P and UDP–>UTP

Both tissues utilize branching enzyme to introduce α1→6 branch points in the growing glycogen chain.

Question 6

Explain the consequences of the different activities of hexokinase and glucokinase

Answer 6

glucokinase = similar function to hexokinase (HK), converts G–> G6P
but not inhibited by G6P
=> HIGH [G6P] in liver acts as “push” mechanism
–> glycogenesis activated without the need of insulin

glucokinase:
1. only in liver, only works on glucose
2. not inhibited by G6P
3. wont reach Vmax at high BGC, high Km

hexokinase:
1. works on any 6C sugar
2. only 1/100th of Km, already starts to max out at high BGC

Question 7

Review the chemical structure of glycogen and the chemical strategy for its synthesis

Answer 7

glycolysis:
glucose (HK)–> G6P –> FGP –> F16BP

Glycogen synthesis
glucose (HK)–> G6P isomerised into G1P –> UDPglucose (activated glucose)
G1P uses UTP (utp so made from RNA sugar) to form UDPglucose = releases PPi

UDPglucose binds onto glycogen chain, and UDP dissociates (uses ATP to convert back into UTP for converting G1P–>UDPglucose) == UDP + ATP –> UTP + ADP

–> always added to the “non-reducing end” on glycogen: 1,4glycosidic bond

glycogen branching enzyme = binds glycogen to glycogen chains, make more new non-reducing ends (1,6 glycosidic ends)
more nonreducing ends = quicker glycogen breakdown

Question 8

Understand how increased glycogen synthesis stimulates glycolysis

Answer 8

glycogen synthase : active when dephosphorylated (like PDH)
–> dephosphorylated by protein phosphatase 1 (PP1)
* glucose –> glycogen

lots of ATP is used in glycogen synthesis, (UDP + ATP –> UTP + ADP)
–> glycolysis stimulated by low energy change, high energy demand
low [AMP] = allosteric regulation on PFK-1 to activate glycolysis to occur

Question 9

Understand what glycemic index is, how it is measured and how it is clinically useful

Answer 9

The glycemic index is a numerical scale that ranks carbohydrates in food based on their impact on blood glucose levels.
= measures how quickly a carbohydrate-containing food raises blood sugar levels.
= high glycemic index : rapidly digested and absorbed/ high BGC

Participants consume a portion of a specific food, blood glucose levels are then monitored over a set period, and the results are compared to a reference food, typically pure glucose or white bread, which has a glycemic index of 100.

Question 10

the role of different glucose transporters in different tissues and how these function

Answer 10

liver is insulin independent, uses GLUT-2 transporters
muscle/adipose (peripheral tissue) need to be activated by insulin to translocate GLUT-4 transportoers to membrane
–> glycogenesis, lipogenesis, glucose oxidation

muscle/WAT
1. insulin enters cell
2. translocate GLUT-4 to surface
3. glucose rapidly enters in response to insulin
4. glucose (HK)–> G6P

G6P (PFK)–> glycolysis
G6P (GS)–> glycogenesis [GS: glycogen synthase]

Question 11

glycogenin

Answer 11

interacts with Glycogen synthase to be fully active
–> can limit the size of glycogen molecule.