lecture 4 glycolysis Flashcards
glucose has 3 paths
storage-> glycogen, starch
oxidation via glycolysis->pyruvate
oxidation via pentose phosphate pathway-> Ribose 5-phosphate
glycolysis
sweet splitting
glucose catabolism
carried out by all cells in cytoplasm
ten reactions
same in all cells
products of glycolysis
pyruvate,atp,NADH
3 fates for pyruvate
aerobic oxidation (CO2+H2O)
anaerobic oxidation into lactate
anaerobic fermentation into alcohol
3 catabolic fates of pyruvate
hypoxic or anaerobic conditions -> 2 ethanol +2CO2
aerobic conditions(CO2 LEAVES)-> Acetyl CoA-> citric acid cycle-> 4 CO2+ 4 H2O
anaerobic conditions -> 2 Lactate (in muscle, erythrocytes, some microorganisms)
one molecule of glucose 6C
degrades to 2 pyruvate molecules 3C
net energy yield of glycolysis
2 ATP and 2 NADH per glucose
glucose + 2NAD+ + 2ADP + 2 Pi
2 pyruvate + 2 NADH + 2 H++ 2 ATP + 2 H2O
glucose + 2 NAD+
2 pyruvate + 2 NADH + 2H+
2ADP + 2 Pi
2 ATP + 2 H2o
overall reaction
is irreversible and exergonic but more energy remains to be extracted
- prepatory phase
4 phases
converts 6 C sugar to 2 3C sugars
USES 2 ATP
payoff phase
6 steps
Converts 2 3C sugars to 2 pyruvates
MAKES 4 ATP (2 from each 3 C sugar)
- phsophorylation of glucose to glucose 6- phosphate
(Mg2+) metal cofactor of hexokinase shields - charges
large negative delta G
priming reaction- ATP is consumed
“traps glucose as glucose 6P which does not diffuse or bind to glucose transporters
- phosphorylation of Fructose- 6P to fructose 1,6 bisphosphate
(Mg2+)
phosphofructokinase-1
phosphoryl group transfer
first committed step, fructose 1,6 P is only targeted for glycolysis
second “priming reaction”
PFK1 activity is highly regulated by ATP levels in the cell
Activity is high when [ATP] is low
Activity is low when [ATP] is high
feedback inhibition
- cleavage of fructose 1,6 bisphosphate
NO Mg
aldolase
aldol condensation
generates isomers:
DHAP and GAP
point where pyruvate formation takes parallel paths
- Conversion of DHAP to GAP
only GAP can be directly degraded to pyruvate
triose phosphate isomerase
ketone to an aldehyde
completes preparatory phase of glycolysis
the splitting of fructose 1,6 bisphosphate
DHAP is made from 1,2,3C
GAP is made from 4,5,6C
split by aldolase
DHAP to GAP done by triose phosphate isomerase
summary of phase 1
4 steps
(5 counting DHAP-GAP)
converts one 6C to two 3C sugars
uses 2 ATP
phase 2: the payoff
6. Oxidation of GAP to 1,3 bisphosphoglycerate
oxidation
payoff: NADH is made when NAD is reduced
1,3 BPG is high energy compound
NOT ATP -> inorganic phosphate
phosphoryl transfer from 1,3 BPG to ADP
phosphoglycerate kinase
transfer from carboxyl P-group
1st ATP is made
“substrate-level phosphorylation”
enzyme named for reverse reaction
(gluconeogenesis)
energy coupling of reactions
coupling processes through a common intermediate: a thioester bond formed between a cysteine in GAP DH enzyme & GAP
example: steps 6 and 7
glyceraldehyde 3P+ ADP + Pi + NAD+ (substrate, endergonic) -> 3P + ATP NADH +H+ (products, exergonic)
overall reaction is exergonic
coupling processes through a common intermediate
a thioester bond formed between a cysteine in a GAP DH enzyme & GAP
thioester intermediate
reduces the delta G of transition energy
8 Conversion of 3-phosphoglycerate to 2-phosphoglycerate
Mg2+ cofactor
phosphoglycerate mutase
a mutase catalyzes the transfer of function group from one position to another on a molecule
(in this case phosphoryl from C3 to C2)
unique phosphorylated His
- Dehydration of 2-phosphoglycerate to phosphoenolpyruvate
Enolase catalyzes the conversion of 2PG to a form from which more energy can be released
standard free energy for the hydrolysis of 2PG is only ~16 kJ / mol
-30 kJ/ mol necessary to drive ATP formation
dehydration of 2 PG to PEP by enolase creates a compound of driving synthesis of ATP
10 phosphoryl transfer from PEP to ADP
final step
substrate level phosphorylation
2nd atp made
pyruvate is made
enzyme named for reverse reaction
summary of phase 2
5 steps
converts GAP to pyruvate
makes 2 ATP (per GAP)
Makes 1 NADH (per GAP)
overall glycolysis summary
overall net reaction of glycolysis is:
glucose +2NAD+ + 2 ADP +2 Pi -> 2 pyruvate + 2 NADH + 2ATP + 2 H2O +2 H+
there is a net gain of 2 ATP per glucose molecule ( actually make 4 , but use 2 )
as glucose is oxidized, 2 NAD + are reduced to 2 NADH
Aerobic - O2 is available
- NADH is reoxidized in the electron transport pathway making ATP in oxidative phosphorylation
- Pyruvate enters the citric acid cycle
Anaerobic conditions
-NADH is re-oxidized to NAD+ providing additional NAD+ for more glycolysis
-pyruvate converted to lactate ( lactic acid fermentation: muscles)
-Pyruvate converted to ethanol( ethanol fermentation yeast)
Fermentation
energy extraction ( i.e. ATP formation via substrate- level phosphorylation) without consumption of oxygen
no net change in concs of NAD+ or NADH
fate of NADH & pyruvate
lactic acid fermentation ( ie muscle contraction)
Conversion of glucose to lactate:
includes two redox reactions, although no net change in oxidation state of carbons in glucose (C6H12O6) vs. lactate (C3H6O3)
no net change in oxidation; H:C ratios the same for glucose & lactate
even so, enough energy ( 2 ATP/ glucose) extracted in conversion of glucose to lactate
fate of NADH & pyruvate
glucose makes 2 pyruvate and reduces 2 NAD to NADH
the 2 NADH oxidize when 2 pyruvate make 2 lactate
fermentation allows for regen of NAD+ in order to extract energy (ATP) from glucose under anaerobic conditions no net change in [NAD+] or [NADH]
ethanol fermentation (ie yeast)
pyruvate loses CO2 from pyruvate decarboxylase to become acetaldehyde
acetaldehyde oxidizes NADH to NAD+ and makes ethanol with alcohol dehyrogenase
Anaerobic fermentation vs oxidative phosphorylation
anaerobic fermentation results in the production of 2 ATP/ glucose
oxidative phosphorylation
can yield up to 38 ATP/glucose
pasteur effect
yeast consume more sugar when grown under anaerobic conditions
hexokinase deficiency
Reduced glucose breakdown
Reduced ATP production
Reduced BPG production
Not as easy for Hb to
assume T-state
PK deficiency
Reduced ATP production
RBCs become deformed/lyse
Hb carries less O2
tumors
have enhanced glucose uptake and glycolysis rates
glucose uptake correlates with tumor aggressiveness and poor prognosis
cancer cells grow more rapidly than blood vessels that nourish them
-They become starved for oxygen (hypoxia)
-Need ATP
hypoxic tumors produce HIF-1
- hypoxia inducible transcription factor
HIF-1 increases gene expression
- glycolytic enzymes
- GLUT 1 and 3
HIF-1 stimulates the growth of vasculature
- expression of signal molecules- vascular endothelial growth factor (VEGF)
- another anti-cancer drug target