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Glycolysis

CA Brown
General Functions
• Provide ATP energy
• Generate intermediates for other
pathways
– Hexose monophosphate pathway
– Glycogen synthesis
– Pyruvate dehydrogenase
• Fatty acid synthesis
• Krebs’ Cycle
– Glycerol-phosphate (TG synthesis)
GLYCOLYSIS
• FUNCTION
– Aerobic: To convert glucose to pyruvate and
ATP. Pyruvate can be burned for energy
(TCA) or converted to fat (fatty acid
synthesis).
• Glucose + 2 ADP + 2 Pi + 2 NAD+ - 2 pyruvate +
2 ATP + 2 NADH + 2 H+
– Anaerobic: ATP production. Recycle NADH
by making lactate.
• LOCATION
– Cytosol of all cells.
Specific tissue functions
• RBC’s
– Rely exclusively for energy
• Skeletal muscle
– Source of energy during exercise, particularly high
intensity exercise
• Adipose tissue
– Source of glycerol-P for TG synthesis
– Source of acetyl-CoA for FA synthesis
• Liver
– Source of acetyl-CoA for FA synthesis
– Source of glycerol-P for TG synthesis
• GLYCOLYSIS ATP YIELDS

• LACTATE OR PYRUVATE
– With oxygen present, pyruvate is oxidized by
the tricarboxylic acid cycle (TCA).
– Without oxygen, pyruvate is reduced to
lactate.
• In muscle, lactate is the usual product.
• Summary of glycolysis 1
Summary of glycolysis 2
CH2OH ATP ADP CH2OP
CH2OP CH2OH
O
O O
OH OH
hexokinase OH
OH OH hexose phosphate isomerase
OH OH OH OH
OH
OH ATP
glucose Glucose-6-phosphate fructose-6-phosphate

ADP
phosphofructokinase
CH2OP
dihydroxy acetone phosphate
C O CH2OP CH2OP
CH2OH O
OH
aldolase
OH
3-phosphoglycerate glyceraldehyde - phosphate dehydrogenase
ATP OH
ADP NADH NAD+ O fructose-1,6-bisphosphate
O O
OP Pi H
O C
C C
H C OH H C OH H C OH

CH2OP
phosphoglycerate kinase CH2OP CH2OP
glyceraldehyde-3-phosphate
1,3-diphosphoglycerate

phosphoglycerate mutase

ATP
H2O O ADP O
O O
O C C
O
C C OP
H C OP C O
pyruvate kinase
CH2OH CH2 CH3
enolase
2 -phosphoglycerate
phosphoenolpyruvate
pyruvate
Hexokinase reaction
CH2OH ATP ADP
CH2OP
O
O
OH
hexokinase OH
OH OH
OH OH OH
OH

glucose Glucose-6-phosphate

• Irreversible
• Kinase (phosphate transfer)
• -16.7kJ
Phosphofructokinase reaction
CH2OP CH2OP
CH2OH CH2OP
ADP
O ATP O
OH OH
OH OH
OH OH
phosphofructokinase fructose-1,6-bisphosphate

• Same as hexokinase reaction


• -14.2kJ
• Major point of regulation
– Committed step
– Stimulated by ADP and AMP
– Inhibited by ATP and fatty acids
Aldolase Reaction
CH2OP
CH2OP CH2OP
C O
O
OH CH2OH
dihydroxy acetone phosphate
OH
OH aldolase
fructose-1,6-bisphosphate
+

O
H
C
H C OH
CH2OP
glyceraldehyde-3-phosphate

• Reverse aldol condensation


• 23.8kJ
• Makes 2 3-Carbon molecules
Pyruvate kinase
ADP ATP
O O
O O
C C
C OP C O
pyruvate kinase
CH2 CH3
phosphoenolpyruvate
pyruvate

• Last reaction….
• Substrate level phosphorylation
• Stabilization of enol - keto
• -31.4kJ
Fates of pyruvate
O
CO2 NAD+ NADH NADH NAD+
O OH
H3C
O
H3C OH O H3C
lactate dehydrogenase (LDH)
pyruvate decarboxylase pyruvate O
ethanol
HSCoA lactate
pyruvate dehydrogenase

CO2
NAD+

NADH
O

H3C SCoA
acetyl CoA
Link Reaction – 2nd stage of respiration
Fates of Pyruvate
• Depend on organism and conditions
• Yeast
– Anaerobic
• Pyruvate decarboxylase
• Makes alcohol
– Aerobic
• Makes acetyl CoA --- energy or fat
• Others
– Anaerobic
• Lactate Dehydrogenase
• Makes lactate
• Sore muscles
– Aerobic
• Acetyl Co A --- energy or fat
• GLYCOLYSIS CONNECTIONS
– Glucose in, pyruvate or lactate out.
– Glucose 6-phosphate to glycogen (reversible).
– Glucose 6-phosphate to pentose phosphates
(not reversible).
– Pyruvate to TCA via acetyl-CoA (not
reversible).
– Pyruvate to fat via acetyl-CoA (not reversible).
Other sugars
• Fructose
– Comes in at fructose-6-p and immediately
phosphorylated
• Lipogenic…after branch to glycogen…makes
acetyl CoA
• Lactose
– Glucose and galactose
• Galactose
– Epimerase turns into glucose-6-P and enters there
• GLYCOLYSIS REGULATION
• Primary signals:
– Insulin turns on.
– Glucagon turns off.
– Epinephrine turns on in muscle, off in liver.
– Phosphorylation turns off in liver, on in
muscle.
Gluconeogenesis
• GLUCONEOGENESIS FUNCTION
– Gluconeogenesis makes glucose from
pyruvate to help maintain blood glucose
levels.
– Uses same enzymes as glycolysis except
where nonequilibrium reactions
– Uses NADPH instead of NADH
• GLUCONEOGENESIS LOCATION
– Liver and kidney—not muscle.
• GLUCONEOGENESIS CONNECTIONS
– Pyruvate in, glucose out.
– Lactate in, glucose out.
– Alanine in, glucose and urea out.
• GLUCONEOGENESIS ATP COSTS
– 2 lactate 6ATP (equivalents) ¡glucose
• Gluconeogenesis in the liver can be fueled by
molecules other than pyruvate or lactate.
• Alanine, a product of protein degradation,
yields pyruvate by simple transamination, and
this pyruvate can be converted to glucose by
the liver and kidney.
• Other amino acids are metabolized to
pyruvate or oxaloacetate, which can also
enter the gluconeogenic pathway.
• In addition, glycerol from the breakdown of
triglycerides in adipose tissue can be used by
the liver and kidney to make glucose
GLUCONEOGENESIS REGULATION

• : Primary signals
– Insulin turns off.
– Glucagon turns on.
– Acetyl-CoA turns on.
– Phosphorylation turns on in liver.

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