Biochemistry Notes: Glycolysis, Krebs Cycle, Gluconeogenesis

Chapter 12
• Glucose
o Early prebiotic conversion of HCHO to glucose
o In ring form, glucose has low tendency to glycosylate proteins
§ As opposed to galactose or mannose
• Cellular Respiration
o Goal is to make ATP
o Aerobic
§ Glycolysis
• First step in aerobic respiration
• CO2 not released
• Otto Meyerhof and Jakub Parnas
o EMP Pathway
• Energy investment phase and energy generation phase
• 1 x glucose à 2 x pyruvate
• No activators or inhibitors if reversible
• Series of 10 reactions
o 1: Glucose + Hexokinase + ATP à Glucose 6-phosphate +
ADP + H+




§
§ Hexokinase = transferase
§ Glucose 6-phosphate = inhibitor
§ Traps glucose inside the cell
§ Irreversible reaction
• Negative DG
§ Glucose 6-phosphate is an important compound at
the junction of metabolic pathways
• Glucose à Glucose 6-phosphate à
glycolysis
• Glucose à Glucose 6-phosphate à
glycogen synthesis
• Glucose à Glucose 6-phosphate à pentose
phosphate pathway
§ Overall: glucose phosphorylated twice, cleaved to
form two trioses, 2 ATP consumed, hexose cleaved
to form two trioses

,o 2: Glucose 6-phosphate + phosphoglucose isomerase <->
fructose 6-phosphate




§
§ Phosphoglucose isomerase = isomerase
§ Reversible
§ Substrate-level phosphorylation
• Direct phosphorylation of ADPàATP
happens on an enzyme
§ Overall: DHAP converted to Gald-3P, two Gald-3P
oxidized to pyruvate, 2 NADH and 4 ATP produced,
substrate-level phosphorylation
o 3: Fructose 6-phosphate + ATP + phosphofructokinase à
fructose 1,6-Bisphosphate + ADP + H+




§
§ Phosphofructokinase = transferase
• Inhibited by ATP binding to the enzyme at
its regulatory site
• Increased by insulin
§ Fructose 2,6-bisphosphate regulates glycolysis in
the liver
• Produced by phosphofructokinase-2
o Fructose 6-phosphate to Fructose
2,6-bisphosphate regulated by PFK-
2
• Allosteric activator of phosphofructokinase-
1
o Inhibited by substrate

, o PFK-1 converts Fructose 6-
phosphate to Fructose 1,6-
bisphosphate
• Happens with high levels of metabolism
• Enzyme activated by glucagon
o High glucagon = low glucose
§ Activates phosphatase
§ Lowers Fructose 2,6-
bisphosphate
o Release of glucagon will stop
glycolysis
• High glucose = high insulin
o Activates phosphofructokinase-2
o Raises Fructose 2,6-bisphosphate
o Insulin and glucagon are never
directly binding
• Reduces Km for Fructose 6-phosphate
• Overcomes inhibition by ATP
§ Irreversible reaction
• Negative DG
§ Activators: AMP, ADP, fructose 2,6-bisphosphate,
insulin
• Insulin is allosteric
§ Inhibitors: ATP, citrate, glucagon
o 4: Fructose 1,6-bisphosphate + aldolase <->
dihydroxyacetone phosphate + glyceraldehyde 3-
phosphate




§
§ Happens in the open-chain form
§ Aldolase = Lyase
§ Reversible reaction
§ Splitting of a 6C compound into two 3C compounds
o 5: Dihydroxyacetone phosphate + triose phosphate
isomerase <-> Glyceraldehyde 3-phosphate

, §
§ Triose phosphate isomerase = isomerase
§ Reversible reaction
o Reactions 6-10 all happen twice
o 6: Glyceraldehyde 3-phosphate + NAD+ + Phosphate +
Glyceraldehyde 3-phosphate dehydrogenase <-> 1,3-
Bisphosphoglycerate + NADH + H+




§
§ Glyceraldehyde 3-phosphate dehydrogenase =
oxidoreductase
• Catalyzes oxidation and phosphorylation at
the same time
§ Generation of NADH
• 2 NADH produced
§ NAD+ + H+ + 2 electrons <-> NADH




•
• Low potential energy goes to high potential
energy
o Reduction of electron carriers
• Reduction of NAD+ to NADH
o Oxidation of NADH to NAD+
• Reversible reaction