Glycolysis Flashcards
overview of glycolysis
involves a sequence of rxns that metabolize 1 molecule of glucose to 2 molecules of pyruvate and generates 2 ATP
(Anaerobic)
Under aerobic conditions can produce more ATP
Fates of Glucose
pyruvate-> ethanol, lactate, complete oxidation (CO2, H2O)
__ is the only fuel the brain can use under conditions of nonstarvation and RBCs can use at all.
glucose
What process can salvage and resynthesize glucose from pyruvate and lactate?
gluconeogenesis
Sources of glucose in diet
disaccharides (sucrose/lactose)
starch
gylcogen
Glucose uptake occurs via what protein carrier?
Glucose transporters (GLUTs)
GLUT1
ubiquitous but expressed highly in brain and RBCs
High affinity
unregulated
GLUT2
Main transporter in liver
low affinity
unregulated
GLUT3
main transporter in neurons
high affinity
unregulated
GLUT4
present in skeletal muscle, heart and adipose tissue
insulin dependent
regulated by insulin
Two stages of Glycolysis
- trapping of glucose and its cleavage into 2 interconvertible 3-carbon molecules
- generation of ATP
first stage of glycolysis
begins with the phosphorylation of glucose by hexokinase and ends with the isomerization of dihydroxyacetone phosphate to glyceraldehyde 3-phosphate (GAP)
5 steps, 3 rxns, no ATP generation, 2 ATP used
Step 1
Glucose phosphorylated to glucose-6-phosphate (G6P). ATP consumed. Enzyme hexokinase (in all tissues) and glucokinase (in liver)
Step 2
G6P isomerized to fructose-6-phosphate (F6P). Enzyme phosphoglucoisomerase
Step 3
F6P phosphorylated to fructose-1,6-bisphosphate (F1,6BP). ATP consumed. Enzyme phosphofructokinase (rate limiting enzyme of glycolysis)
Step 4
F1,6BP broken down to glyceraldehyde-3phosphate (G3P) and dihydroxyacetone phosphate (DHAP). Enzyme is aldolase
Step 5
DHAP isomerized to G3P. Enzyme triose phosphate isomerase
Second stage of glycolysis
Energy harnessed in GAP used to form ATP
GAPDH step
Oxidative phosphorylation of GAP to form 1,3-BPG Reduce NAD+ to NADH 1,3-BPG has high phosphoryl- transfer potential NADH contains a pair of “high energy” electrons Sent to electron transport chain (ETC), play role in oxidative phosphorylation (OXPHOS)
Phosphoglycerate kinase/mutase step
The kinase converts 1,3 BPG to 3-PG ADP is phosphorylated to form ATP and 3-PG Via substrate transfer The mutase moves phosphate from 3rd to 2nd position (2-PG)
Enolase/Pyruvate kinase step
Dehydration of 2-PG by enolase forms PEP, an enol with high phosphoryl-transfer potential (unstable) Then, Pyruvate kinase transfers phosphoryl group from PEP to ADP to form ATP PEP is converted from unstable enol to pyruvate, a stable ketone This step is irreversible
Fates of Pyruvate
Pyruvate can be reduced to lactate, with the regeneration of NAD+ Pyruvate can be oxidized aerobically via the citric acid cycle after first undergoing an oxidative decarboxylation to form acetyl CoA Yeast and some other microorganisms can convert pyruvate to ethanol – maintain redox balance
Regeneration of NAD+
when pyruvate is converted to lactate, NADH is converted to NAD+. this NAD+ goes back and works in the reaction with GAP.
Sucrose
disaccharide of glucose and fructose
Lactose
disaccharide of glucose and galactose
Fructose and galactose are converted into
glycolytic intermediates
Fructose
quickly turned to fat in times of high energy
Major regulatory enzymes of Glycolysis
– Hexokinase
– Phosphofructokinase
– Pyruvate kinase
Regulation of Glycolysis in Muscle
Goal: To generate ATP during activity ATP levels regulate glycolysis
at rest glyc is inhibited and during exercise it is stimulated (contraction)
Regulation of Glycolysis in Liver
Goal: To maintain blood glucose levels To provide building blocks for other pathways (in response to biochemical diversity and need)
Enzymes: phosphofructokinase, glucokinase, pyruvate kinase
Phosphofructokinase
Activated by F-2,6-BP Inhibited by citrate
Glucokinase
No hexokinase in liver Glucokinase is not inhibited by glucose 6-phosphate – Glucose permanently trapped
Pyruvate kinase
regulated by allosteric effectors and covalent modification
Excessive fructose consumption
can lead to pathological conditions
