Lecture 4 - Introduction to Metabolism - Glycolysis I

Question 1

3 major purposes of metabolism:

Answer 1

(1) performance of mechanical work in muscle contraction and cellular movements

(2) the active transport of molecules and ions (such as neurones)

(3) the synthesis of macromolecules and other biomolecules from simple precursors

Question 2

what is meant when metabolism is referred to as being “compartmentalised”?

Answer 2

each stage of metabolism takes place in a specific place (compartment) e.g: glycolysis → cytoplasm, link reaction + krebs (TCA) cycle → mitochondrial matrix, oxidative phosphorylation → mitochondrial inner-membrane

Question 3

Warburg Effect:

Answer 3

in tumours and other proliferating or developing cells, the rate of glucose uptake dramatically increases and lactate is produced, even in the presence of oxygen and fully functioning mitochondria

Question 4

catabolism & anabolism:

Answer 4

catabolism: the breakdown of energy-rich molecules (carbohydrate / lipid / protein) to simpler ones (C02 , H20 and NH3) with the energy released being “conserved” as adenosine triphosphate (ATP), for use in anabolic reactions

anabolism: the synthesis of complex molecules from simpler ones (e.g. glycogen from glucose) with the energy necessary for synthesis being usually derived from ATP

Question 5

metabolism:

Answer 5

describes the integrated set of chemical reactions occurring in the body and comprises both anabolism and catabolism

Question 6

what are the three phases of glycolysis?

Answer 6

(1) energy investment stage

(2) the cleavage

(3) energy generation phase

Question 7

Gibbs Free Energy:

Answer 7

the energy derived from the oxidation of dietary fuels (primarily carbohydrates and lipids)

this energy is transduced into useful work e.g: biosyntheses, transport of metabolites and it is converted into ATP

Question 8

what determines whether a reaction can occur?

Answer 8

the free energy change ∆G determines whether a reaction can occur

Question 9

glycolysis - energy investment phase 1:

Answer 9

Glucose is phosphorylated by Hexokinase to form Glucose 6-phosphate

[gets shrek phosphate ears]

Question 10

glycolysis - energy investment phase 2:

Answer 10

the atoms of glucose-6-phosphate is rearranged (isomerised) by phosphoglucose-isomerase (PGI)/Phosphohexose-isomerase to form fructose-6-phosphate

Question 11

glycolysis - energy investment phase 3:

Answer 11

fructose-6-phosphate is phosphorylated by phosphorus-fructokinase-1 to give fructose-1,6-biphosphate

Question 12

glycolysis - energy investment phase 4:

Answer 12

fructose-1,6-biphosphate is then cleaved in half by aldolase to give glyceraldehyde-3-phosphate and dihydroxyacetone

Question 13

endergonic reactions:

Answer 13

chemical reaction in which the standard change in free energy is positive

Question 14

the cleavage and salvage of DHA:

Answer 14

dihydroxyacetone is isomerised by triosephosphate isomerase (TPI) to give Glyceraldehyde-3-phosphate

Question 15

energy generation phase - 1:

Answer 15

glyceraldehyde-3-phosphate (GAP) is oxidised and phosphorylated by glyceraldehyde-3-phosphate-dehydrogenase to form 1,3-biphosphoglycerate

Inorganic phosphate is used instead of ATP as the substrate. NAD is reduced to NADH as the result of oxidation of GAP

Question 16

what reactions are coupled in glycolysis?

Answer 16

GAP oxidation & Acyl-phosphate formation are coupled

Oxidation of aldehyde to carboxylic acid by NAD+ and phosphorylation of the acyl group of GAP are coupled

Tow reactions are taking place NOT in succession

High-energy thioester intermediate (facilitated by the enzyme) provide energy for the latter exergonic reaction

Question 17

energy generation phase - 2:

Answer 17

1,3-Bisphosphoglycerate is used to phosphorylate ADP by Phosphoglycerate kinase to form 3-phosphoglycerate and ATP by substrate-level phosphorylation

Question 18

energy generation phase - 3:

Answer 18

The position of phosphoryl group of 3-phosphoglycerate is rearranged by Phospho-glycerate mutase to give 2-phosphoglycerate

Question 19

energy generation phase - 4:

Answer 19

2-phosphoglycerate is dehydrated by Enolase to give Phosphoenolpyruvate

Question 20

energy generation phase - 5:

Answer 20

Phosphoenolpyruvate donates the phosphoryl group to ADP by Pyruvate kinase to give Pyruvate

Question 21

exergonic reaction:

Answer 21

chemical reaction in which the change in free energy is negative

Question 22

points to revise regarding the pathway:

Answer 22

•Define the substrate and end-product of the enzymes of Glycolysis

•Link the role of enzyme and what it does – pay attention to the verb!

•Clear about if the reaction is endergonic or exergonic - overall type of reaction

Question 23

energy charge (EC):

Answer 23

an index used to measure the energy status of a cell and is related to the cellular concentrations of the adenylate nucleotides

                                  [ATP] + 0.5[ADP]
                             ——————————-  Energy charge  =    [ATP] + [ADP] + [AMP]

Question 24

range of EC in most cells:

Answer 24

0.8-0.95

Question 25

what does AMP serve as?

Answer 25

a signal for energy demand as it is a signal of the low energy state for this enzyme PFK1

Question 26

what is Phosphofructokinase-1 (PFK-1) activity is promoted and inhibited by?

Answer 26

AMP - promotes PFK-1 activity through reversing the allosteric inhibition of PFK-1 (+)

ATP - allosterically inhibits PFK-1 ( - )

Question 27

___ serves as an allosteric activator of PFK

Answer 27

AMP

Question 28

what is pyruvate kinase (PK) promoted by?

Answer 28

fructose-1,6-biphoshate

Question 29

what two activities are both allosterically inhibited by ATP?

Answer 29

Phosphofructokinase (PFK) and Pyruvate kinase (PK) activitY

Question 30

three key regulatory steps in glycolysis:

Answer 30

(1) HK (Hexo Kinase)

(2) PFK (Phospho-Fructo-Kinase)

(3) PK (Pyruvate Kinase)

Question 31

glycolysis regulation occurs in response to the:

Answer 31

energy charge of the cell and hence ATP, ADP, and AMP all serves as regulatory molecule