Lecture 4 - Introduction to Metabolism - Glycolysis I Flashcards
3 major purposes of metabolism:
(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
what is meant when metabolism is referred to as being “compartmentalised”?
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
Warburg Effect:
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
catabolism & anabolism:
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
metabolism:
describes the integrated set of chemical reactions occurring in the body and comprises both anabolism and catabolism
what are the three phases of glycolysis?
(1) energy investment stage
(2) the cleavage
(3) energy generation phase
Gibbs Free Energy:
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
what determines whether a reaction can occur?
the free energy change ∆G determines whether a reaction can occur
glycolysis - energy investment phase 1:
Glucose is phosphorylated by Hexokinase to form Glucose 6-phosphate
[gets shrek phosphate ears]
glycolysis - energy investment phase 2:
the atoms of glucose-6-phosphate is rearranged (isomerised) by phosphoglucose-isomerase (PGI)/Phosphohexose-isomerase to form fructose-6-phosphate
glycolysis - energy investment phase 3:
fructose-6-phosphate is phosphorylated by phosphorus-fructokinase-1 to give fructose-1,6-biphosphate
glycolysis - energy investment phase 4:
fructose-1,6-biphosphate is then cleaved in half by aldolase to give glyceraldehyde-3-phosphate and dihydroxyacetone
endergonic reactions:
chemical reaction in which the standard change in free energy is positive
the cleavage and salvage of DHA:
dihydroxyacetone is isomerised by triosephosphate isomerase (TPI) to give Glyceraldehyde-3-phosphate
energy generation phase - 1:
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
what reactions are coupled in glycolysis?
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
energy generation phase - 2:
1,3-Bisphosphoglycerate is used to phosphorylate ADP by Phosphoglycerate kinase to form 3-phosphoglycerate and ATP by substrate-level phosphorylation
energy generation phase - 3:
The position of phosphoryl group of 3-phosphoglycerate is rearranged by Phospho-glycerate mutase to give 2-phosphoglycerate
energy generation phase - 4:
2-phosphoglycerate is dehydrated by Enolase to give Phosphoenolpyruvate
energy generation phase - 5:
Phosphoenolpyruvate donates the phosphoryl group to ADP by Pyruvate kinase to give Pyruvate
exergonic reaction:
chemical reaction in which the change in free energy is negative
points to revise regarding the pathway:
•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
energy charge (EC):
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]
range of EC in most cells:
0.8-0.95
what does AMP serve as?
a signal for energy demand as it is a signal of the low energy state for this enzyme PFK1
what is Phosphofructokinase-1 (PFK-1) activity is promoted and inhibited by?
AMP - promotes PFK-1 activity through reversing the allosteric inhibition of PFK-1 (+)
ATP - allosterically inhibits PFK-1 ( - )
___ serves as an allosteric activator of PFK
AMP
what is pyruvate kinase (PK) promoted by?
fructose-1,6-biphoshate
what two activities are both allosterically inhibited by ATP?
Phosphofructokinase (PFK) and Pyruvate kinase (PK) activitY
three key regulatory steps in glycolysis:
(1) HK (Hexo Kinase)
(2) PFK (Phospho-Fructo-Kinase)
(3) PK (Pyruvate Kinase)
glycolysis regulation occurs in response to the:
energy charge of the cell and hence ATP, ADP, and AMP all serves as regulatory molecule
