Lecture 10: Glycolosis Flashcards
Feedback inhibition
- regulated the whole metabolic pathway (production of amino acids)
• Metabolic pathway includes:
1. threonine
2. alpha-ketobutyrate
3. Isoleucine - each rxn there there is an enzyme
- Isoleucine will bind to the first enzyme in order to inhibit it
Multiple Feedback Control
- allows cells to adjust the ratio of different compounds (e.g amino acids)
Enzyme Regulation
a) Competitive Inhibition
b) Allosteric Regulation
Competitive inhibition
- The substrates cannot
bind when a regulatory
molecule binds to the
enzyme’s active site.
Allosteric Regulation
• Allosteric Activation: - The active site becomes available to the substrates when a regulatory molecule binds to a different site on the enzyme. or: • Allosteric Inhibition: - The active site becomes unavailable to the substrates when a regulatory molecule binds to a different site on the enzyme. *each time, the shape of the enzyme changes* *most common type of regulation*
How is Allosteric Inhibition more efficient?
- comes down to number of regulator molecules that you need
- Competitive inhibition you need 10 million molecules and maybe 1 million regulators
- Allosteric regulator you have 1 regulator: 10 molecules (therefore, less energy)
Cooperative Allosteric Transition
- occurs with two or more subunits
- inhibitor can bind to the enzyme in the place of a substrate.
- It is a difficult transition for the inhibitor to be added, when the enzymes already binded
- it is an easy transition when one inhibitor and one substrate are in and the inhibitor can be added.
Cooperative Allostery
• when multiple subunits bind together
- results in different reaction curve
- the more subunits, the steeper the slope meaning that the enzyme activity lowers a lot faster with more subunits
- some delay at the beginning because it takes a while to bind (first is hardest, then gets easier)
Firs step in Metabolic Pathway
- nearly always a multisubunit enzyme negatively regulated by cooperative allostery
Glycolosis
- when glucose is broken down, it produces energy - must be done in little steps to minimize the amount of energy lost
- complete oxidation of glucose is exergonic
- about half of the energy from glucose is collected in ATP (endergonic)
Energy for Life
- sun allows photosynthesis which allows for stored chemical energy which allows for glycolysis
- glycolysis can be aerobic or anaerobic
Aerobic Glycolysis: Cellular Respiration
- complete oxidation
- waste products: H2O, CO2
- net energy trapped: 29 ATP
Anaerobic Glycolysis: Fermentation
- incomplete oxidation
- waste products: organic compound
- net energy trapped: 2 ATP
Redox Reactions
• Transfer electrons
• Made up of 2 half reactions/redox pairs . (meaning one side electrons are collected, then transferred)
- A gain of electrons or hydrogen atoms is called reduction.
- The loss of electrons or hydrogen atoms is called oxidation.
How do you recognize oxidations?
- Fe+2 to Fe+3
- adding a hydrogen meaning you are oxidization (removing an electron, thus increasing the hydrogens)
Oxidation of Organic Molecules
- decreases the number of C-H bonds
- due to the attraction the electrons have to oxygen atoms, more than carbon.
NAD
- cofactor
- essential electron carrier in cellular redox reactions
- intermediate within the reaction
NAD+
- gives up electrons (from glucose) to oxygen (electronegative acceptor)
- Has alternating double bonds that are energetically favoured because of the electrons of all 3 electron pairs form a common electron cloud. This makes it very stable
- forms into NAHH by breaking down glucose and accepting electrons (i.e getting reduced)
Oxidation of NADH with O2 as electron accepter
- exergonic NADH + H+ + 1/2 O2 → NAD+ + H2O • Two half reactions or redox pairs: 1. NADH NAD+ + H+ + 2e- (oxidation) 2. 1/2 O2 + 2H+ + 2e- H2O (reduction) - NADH gives up electrons, oxygen takes those and becomes water.
Redox potential
- the tendency to lose or gain electrons
- a positive redox potential means that thy will have a tendency to gain electrons (become reduced)
- a negative redox potential means they will have a tendency to loose electrons (become oxidized)
Stages of Glycolysis
- Investment of ATP to activate the sugar followed by splitting of C6 into 2x C3
- Oxidation of C3 giving NADH + H+ and ATP followed by recovery of initial ATP investment (investment is required to rearrange the sugar to be oxidized)
Glycolysis coverts glucose to pyruvate (Part 1)
- First reaction is catalyzed by HEXOKINASE - forms G6P (adds a phosphate bond)
- Second reaction is catalyzed by PHOSPHOHEXOSE ISOMERASE (creates symmetry for breakup into two 3-C molecules- forms F6P)
- Third reaction is catalyzed by PHOSPHOFRUCTOKINASE (catalyses based on energy levels in cells) (adds another phosphate group to the molecules to make it more symmetrical- forms FBP)
Glycolysis coverts glucose to pyruvate (Part 2)
- takes FBP and splits into 2 3-C molecules called G3P
Glycolysis coverts glucose to pyruvate (Part3)
- G3P is oxidized
- NAD+ is reduced to NADH +H+
- this exergonic reaction releases enough energy to phosphorylate the molecules, forming BPG
- 1,3-bisphosphoglycerate donates one of its phosphate groups to ADP making a molecule of ATP and turning into 3-
phosphoglycerate in the process.
Glycolysis coverts glucose to pyruvate (Part 4)
- 3- phosphoglycerate is converted into its isomer, 2-phosphoglycerate.
- 2-phosphoglycerate loses 2 molecules of water, becoming phosphoenolpyruvate (PEP). PEP is an unstable molecule, poised to lose its phosphate group in the final step of glycolysis.
- PEPP, readily donates its phosphate group to ADP, making a second molecule ATP. As it loses its phosphate, PEP is converted pyruvate; the end product of glycolysis. (overall there are 2 pyruvate)
Substrate- level phosphorylation
- results in the formation of ATP or GTP by the direct transfer of a phosphoryl (PO3) group to ADP or GDP
Unfavourable reactions
- Have positive ∆G
* can be directly coupled to favourable ones (hydrolysis of ATP) or indirectly by sequential coupling.
Where does pyruvate Oxidation occur?
• In mitochondria
- carboxyl group is removed (released as CO2)
- NADH is released
- NAD+ is added along with Coenzyme A
- this results in Acetyl Coenzyme A
