week 8: glycolysis regulation, pyruvate dehydrogenase, and citric acid cycle Flashcards
what happens to fructose-6-phosphate in the liver at higher glucose concentration? (enzyme, energy changes, final product)
converted to fructose-2,6-bisphosphate by liver PFK2 (dephosphoenzyme) and converts and ATP to an ADp
what happens to fructose-2,6-bisphosphate in the liver at lower glucose concentrations? (enzyme, energy changes, final product)
converted by liver FBPase-2 (phosphoenzyme) to fructose-6-phosphate and forms Pi from H2O
is fructose-2,6-bisphosphate a part of glycolysis
no
what intermediate from glycolysis does fructose-2,6-bisphosphate come from?
fructose-6-phosphate
what enzyme is the main control point in glycolysis
phosphofructokinase
how does fructose-2,6-bisphosphate regulate phosphofructokinase
activates it – inhibits corresponding enzyme in gluconeogenesis
which enzymes are the three irreversible steps in glycolysis catalyzed by?
hexokinase
phosphofructose kinase
pyruvate kinase
why would we need to reverse glycolysis
the brain, nervous system, and red blood cells only use glucose for ATP synthesis, so need gluconeogenesis after vigorous exercise or prolonged fasting to quickly regenerate glucose levels
characteristics of hexokinase
hexokinase can catalyze a variety of reactions (nonspecific), lower km, inhibited by G6P
characteristics of glucokinase
glucokinase is hexokinase of liver and only works on glucose – much higher km (only works at high [glucose]), not inhibited by G6P
how are hexokinase and glucokinase related and when is one used over the other
they are isozymes and can catalyze the same reaction
glucokinase is enzyme in the liver and because of high km only works at higher [glucose]
why do most tissues use hexokinase (over glucokinase)
metabolize blood glucose for energy, the G6P is trapped in the cell, so there is only product inhibition once you have enough glucose for energy
why does the liver use glucokinase over hexokinase?
it must maintain blood glucose, so when there is high blood glucose is uses glucokinase to store it as glycogen, and it is not inhibited by G6P so it can take up excess glucose and store it
when would the liver use hexokinase? (in addition to glucokinase)
keeps a little hexokinase around to do glycolysis for energy when glucose levels are normal/low
how are glucokinase and hexokinase regulated by substrate availability?
glucokinase is highly regulated by substrate availability due to Km being nearer to normal glucose levels while hexokinaase has a lower km than normal levels so it’s not really affected by substrate availability
how does the cell know when it needs ATP? how is glycolysis regulated to respond to this condition?
high ADP/AMP concentrations tell the cell it needs ATP and will activate PFK-1 and pyruvate kinase
which of the three regulated enzymes in glycolysis is the main control point
phosphofructokinase
what enzyme is considered the secondary control point in glycolysis?
pyruvate kinase
how is pyruvate kinase regulated by the need for glycolysis
fructose 1,6 bisphosphate activates (strongest regulator); Acetyl-coA and NADH inhibits
how is pyruvate kinase regulated by ATP
ATP inhibits, and ADP/AMP activate
what inhibits phosphofructokinase
citrate
what inhibits pyruvate kinase
acetyl coA and NADH
what activates phosphofructokinase (PFK)
AMP/ADP, fructose-2,6-bisphosphate
what inhibits PFK
ATP, citrate
anaerobic glycolysis substrate/product summary
glucose + 2ADP + 2pi –> 2 lactacte + 2 ATP + 2H2O
process of alcoholic fermentation in yeast
pyruvate –pyruvate carboxylase–> acetaldehyde –alcohol dehydrogenase–> ethanol
what are the 2 primary sources of energy for cancer cells?
glucose and glutamate (but can use any of intermediates of glycolysis as well)
how do cells get energy
from C atom oxidation
where does the TCA cycle occur?
mitochindrion
what are semipermeable membranes permeable to and what is mechanism
hydrophobic (nonpolar) molecules (O2, CO2), small, uncharged molecules (H2O) get in by diffusion
what are semipermable membranes impermable to and how do those get across?
large, polar, charged molecules get across via mediated transport system
what are 2 types of mediated transport
passive: facilitates diffusion
active: uses energy to go against concentration gradient
what is a uniport
single channel allows single molecule to go one direction
what is a symport
single channel which allows 2 substrates to go in same direction
what us an antiport
single channel which allows 2 substrates to go in opposite direction
what/how/why is the mitochondrial outer membrane permeable to?
has a protein called porin which punches holes in it so permeable to molecules smaller than 5Kd by diffusion
feature of mitochondrial inner membrane
larger surface area due to folds (cristae)
what do the cristae due
increase surface area, allow for localized buildup of concentration to control contents of matrix, provides scaffold for ETC to occur
how is pyruvate imported into the mitochondria
a symport with H+
where does the citric acid cycle occur in eukaryotes
the mitochondrial matrix
how do cristae relate to respiratory activity of cell
more cristae = more surface area = more e- transport chain complexes which give more respiration
what is oxidative carboxylation
synthesis of acetyl coa from pyruvate
what is the use of acetyl coa
its a high energy compound, so cleavage can provide energy to drive the TCA cycle
what are sources of acetyl coa and how are these used
amino acids (proteins), fatty acids (lipids), glycolysis (carbohydrates) are all used as sources for acetyl coa in the first stage of cellular respiration
what components make up pyruvate dehydrogenase; what kind of enzyme is this
E1, E2, and E3 – a multienzyme complex
what is E1 (in pyruvate dehydrogenase)
pyruvate decarboxylase
what is E2 in pyruvate dehydrogenase)
dihydrolipoyl transacetylase
what is E3 in pyruvate dehydrogenase)
dihydrolipoyl dehydrogenase
what are 2 benefits of multienzyme complexes?
- enhanced reaction rates due to channeling of intermediates and limited side reactions
- coordinated regulation
how does thiamine pyrophosphate (TPP) work in pyruvate dehydrogenase
a cofactor bound to E1 which decarboxylates pyruvate yielding a hydroxyethyl-TPP carbanion – has an acidic proton
