Carbohydrates (Lecture 3)

Question 1

how is creatine phosphate an immediate reservoir for ATP?

Answer 1

cells can’t store free ATP (as for this would inhibit ATP synthase)

the ATP is stored by generating Creatine-P which can remobilize ATP

Question 2

steps involved in ATP production via creatine

Answer 2

1. ETC will create a proton gradient
2. ATP synthase uses this gradient to generate ATP
3. ATP will be transporter via AAC ATP/ADP carrier into the inner mitochondrial matrix
4. creatine kinase can convert creatine into creatine-P with ATP

when ATP is in low amount, the creatine kinase can partake in the reverse reaction, thus the accumulation of ADP will convert creatine-P into creatine and produce ATP

Question 3

what is the regulatory step of glycolysis?

Answer 3

Hexokinase

the first step

Question 4

what happens once glucose enters the cell?

Answer 4

the glucose will be phosphorylated by hexokinase (the regulatory step)

Question 5

what is the first step in glycolysis?

Answer 5

glucose + ATP + Mg 2+ are converted into glucose-6-phosphate (G6P) via hexokinase

Question 6

what are the advantages of hexokinase phosphorylation?

Answer 6

glucose sequestration, by trapping glucose inside the cell

thermodynamically, this keeps the glucose concentrations low within the cell (cytoplasmic), thus promoting passive diffusion of more glucose into the cell

Question 7

hexokinase has a substrate specificity for…

Answer 7

hexoses

Question 8

which enzyme has higher affinity for glucose? (hexo/gluco-kinase)

Answer 8

hexokinase

Question 9

what is hexokinases modulator?

Answer 9

G6P (product inhibition)

Question 10

where is glucokinase found and what does it do?

Answer 10

found in the liver/pancreas and it converts glucose and ATP into G6P and ADP

Question 11

what is glucokinases modulator?

Answer 11

glucokinase regulatory protein (GKRP)

Question 12

what is GKRP and how does it work?

Answer 12

binding partner that sequesters glucokinase in the nucleus when glucose levels are low
, therefore when glucose levels are high, the GKRP will release the enzyme in order to promote the production of G6P and promote the production of energy

Question 13

what is the second step fo glycolysis?

Answer 13

the first reversible step converting G6P into F6P via phosphoglucose isomerase

Question 14

how is phsophoglucose isomerase (PGI) driven?

Answer 14

by substrate concentration

Question 15

what is the third step in glycolysis?

Answer 15

F6P is converted to fructose 1,6 bisphosphate (F1,6BP) with the addition of ATP and the enzyme phosphofructokinase (PFK)

this is the committing step for metabolizing glucose

Question 16

how is PFK activated?

Answer 16

PFK is regulated by AMP and F26P

Question 17

how is PFK inhibited?

Answer 17

ATP and citrate

Question 18

explain the allosteric regulation of PFK

Answer 18

in the presence of ATP, PFK1 will be in the T (tense) inactive state. this is because ATP inhibits PFK

in the presence of high AMP, thus low ATP, PFK1 will shift to the R (relax) state. the relax state will trigger the conversion of F6P to F1,6P

Question 19

is AMP or ATP more potent at regulating PFK?

Answer 19

PFK is more sensitive to AMP, as for AMP overcomes the ATP inhibition of PFK1

Question 20

what is the function of ADK (adenylate kinase)?

Answer 20

regeneration of ATP

2ADP –> ATP +AMP

ADENYLATE KINASE can keep ATP abundant for exercise, but it can also regenerate AMP in order to activate the PFK, thus stimulating glycolysis and the production of energy

Question 21

how is PFK regulated with Fructose-1,6-bisphosphate.

Answer 21

substrate cycling, where there is differential regulation

Question 22

what occurs with PFK during exercise?

Answer 22

during exercise, glycolysis will be favoured in order to generate more energy

the conversion of G6P to F6P is favoured and the conversion of F6P to F1,6BP is favoured with the addition of an ATP molecule

this in turn will also allow F1,6BP to be converted into GAP and DHAP

the ADP generated in this reaction will b e converted to ATP and AMP via ADK, thus activating PFK further

Question 23

explain F2,6 bisphosphate’s role in glycolysis?

Answer 23

F2,6P is a potent activator of PFK, but it is not a substrate of glycolysis

F2,6BP also functions to inhibit FBPase-2 (which converts F1,6BP into F2,6BP.

F2,6BP is made via PFK2

Question 24

what are the regulators of PFK2?

Answer 24

glucagon (liver) and epinephrine (heart muscle)

Question 25

what occurs in the differential hormonal regulation of PFK2 enzyme in the liver isozyme?

Answer 25

during fasting/prolonged exercise:

the sensing of low glucose by pancreatic alpha cells secretes glucagon, which increases cAMP and allows PKA activity

decrease in blood glucose, promotes gluconeogenesis by inactivating PFK2 (via phosphorylation by PKA) and activating FBPase in order to convert F2,6BP into F1,6BP and then further into F6P and then G6P

Question 26

what occurs in the differential hormonal regulation of PFK2 enzyme in the heart muscle isozyme?

Answer 26

in conditions of stress:

epinephrine levels are high, cAMP levels ar also high and PKA is active

this promotes glycolysis and activates PFK1 to form GAP + DHAP