MCB Exam 4

1. fed state: increases glycolysis
2. Fasted state: glycolysis is not increased
-glucose levels are low
-brain needs glucose, other tissues can use fat for fuel
3. Glycolysis and gluconeogenesis share 7 reactions
-can't happen at the same time or the same rate
-equilibrium reactions (use same enzyme to go back and forth)
4. Oxidation-reduction reactions
5. main point of energy transformation is to transform bond energy into ATP

*Function: to produce ATP and other intermediates
*ATP invested, need to put ATP into reactions
-recover ATP later
*ATP and NADH is generated

*Glucose + 2ADP + 2Pi + 2NAD+ -> (10 reactions) -> 2 pyruvate + 2ATP (net) + 2NADH + 2H+ + 2H20
*glucose oxidized to pyruvated
-pyruvate has 3 carbons
-energy released = -96 KJ/mol (-23 kcal/mol)
*NAD+ reduced to NADH (potential energy)
- NAD+ is capturing electrons as glucose is oxidized
-reaction is in equilibrium and reversible
*ALL ENERGY TRANSFORMATIONS ARE OXI/RED REACTIONS

*Each reaction releases little energy instead of a lot
-less energy is lost as heat
*energy can be captured in a way that the cell can use it
*hierarchy of control in terms of energy released

*initial step of multiple pathways using gluco and hexokinase (found in liver)
**REMEMBER: glucokinase is a high Km enzyme, Hexokinase has a low Km
-glucokinase predominate in fed state when [glucose] is high (5-10mM), hexokinase already saturated at lower concentrations
*facilitated transport, concentration dependent
-transporter can work in both directions
*purpose of phosphorylation is to trap glucose inside the cell by adding a negative charge, so transporter cant be transported back outside of cell
-commits glucose to be metabolized in fed state (glycolysis, pentose phosphate pathway, glycogen synthesis)

*phosphorylation to glucose-6-phosphate
-Hexokinase/Glucokinase: important regulated step
-reaction is favorable because ATP is hydrolyzed
*investment reaction (ATP ---> ADP)
-provides phosphate and driving force for reaction to go forward
-coupled reaction
*energy released = -16.7 KJ/mol
-only negative because ATP was utilized
-1st of the 3 regulated steps

*Isomerization: Aldose ----> Ketose
-both have 6 carbons
- Isomerizations = reversible with the same enzyme
*prepare intermediate for another step
-want to get intermediate into chemical form where it can be acted on

*phosphorylation: rate-limiting step - commits glucose to glycolysis
*Highly regulated
*phosphorylate fructose -6- phosphate ---> Fructose-1,6-biphosphate
-catalyzed by PFK-1
*rate-controlling step that controls speed of all succeeding reactions, highly regulated by energy charge
-If AMP increases, low energy charge, PFK speeds up
-if ATP increases, high energy charge, PFK slows down

*Cleavage: everything is double from this point on
- Dihidroxyacetone phosphate (1st 3 carbons from F-1,6-BP) is present at 96% @ equilibrium
-Glyceraldehyde-3-phosphate (2nd 3 carbons): isomer of DAP
*although DAP is more produced, GAP is what is used and results in further conversion of DAP to GAP

*Isomerization
-Dihydroxyacetone ---> Glyceraldehyde-3-phosphate
-so far have not gained/generated any energy
-invested 2 ATP molecules so far

*Oxidation/reduction: occur in pairs
-an aldehyde is oxidized to a carboxylic acid and NAD+ is reduced to NADH with transfer of 2 electrons
-catalyzed by GAP-DH
*energy of carbon oxidation is captured as high phosphoryl transfer potential
-1,3-BPG has high phosphoryl transfer portential, has more energy than ATP so it can synthesize ATP
-NAD+ ---> NADH in oxidation of aldehyde = favorable
*acyl phosphate intermediate formation (dehydration) binds to enzyme GAPDH with thioester bond = not favorable
-enzyme GAPDH cleaves bond to release energy to drive reaction
*S comes from cysteine in GAPDH
*Very important step: begin to harvest energy

*from generated 1,3-bisphosphoglycerate intermediate
* 2 high-energy bonds : 1,3bisphosphoglycerate and thioester bond
*Nicaotinamide is derived from the B vitamin, niacin
-B vitamins generate NAD and FADH

*Substrate-level phosphorylation
-use 1,3-bisphosphoglycerate to phosphorylate ADP --> ATP + 3-phosphoglycerate
*2 ATP produced per glucose
-balances 2 ATP output
-at this point, ATP has been recovered
-everything is doubled because of step 4 (cleavage)

*Any bond that can be hydrolyzed with the release of greater than or the equivalent energy as ATP
*PEP: uses energy to phosphorylate ADP --> ATP
-used in last step of glycolysis
-synthesis of ATP from high-energy intermediates = substrate-level phosphorylation (happens without O2)

*1,3-bisphosphoglycerate
*phosphoenolpyruvate (PEP)