Section 7 - Glycolysis and Gluconeogenesis
● Glycolysis: t he sequence of reactions that converts one molecule of glucose into two
of pyruvate while generating ATP
○ Major functions
■ Generating ATP
■ Provide building blocks for biosynthesis
● Gluconeogenesis: process to synthesize glucose
Chapter 16 - Glycolysis
● Why is glucose such a prominent fuel?
○ It’s one of several monosaccharides formed from formaldehyde under
prebiotic conditions → available as a fuel source for primitive biochemical
systems
○ It’s the most stable hexose because the hydroxyl groups and the
hydroxymethyl group are all in the equatorial position → minimizes steric
clashes
○ It has a low tendency to nonenzymatically glycosylate proteins
16.1 - Glycolysis Is an Energy-Conversion Pathway
● Eukaryotic cells → glycolysis takes place in the cytoplasm
● Glucose → 2 pyruvate + 2 ATP
● Enzymes of glycolysis are organized into complexes
○ eg. in yeast → glycolytic enzymes are associated with
the mitochondria
○ eg. in mammalian erythrocytes (red blood cells) →
glycolytic enzymes are found bound to the inner
surface of the cell membrane
○ Arrangement increases enzyme efficiency by
facilitating the movement of substrates and products
between enzymes (substrate channeling) and
prevents the release of any toxic intermediates
● Glycolysis → 2 stages
○ Stage 1: trapping and preparation
■ No ATP is generated
■ Conversion of glucose into fructose
1,6-biphosphate
● Phosphorylation → Isomerization →
phosphorylation
■ Cleavage of the fructose 1,6-biphosphate into
2 phosphorylated three-carbon fragments
○ Stage 2
■ ATP is harvested when three-carbon
fragments are oxidized to pyruvate
, ● Glucose enters the cell through specific transport proteins and has one principal fate
○ It is phosphorylated by ATP to form glucose 6-phosphate
○ Notable because:
■ Glucose 6-phosphate cannot pass through the membrane to the
extracellular side, because it is not substrate for the glucose
transporters
■ The addition of the phosphoryl group facilitates the metabolism of
glucose to the phosphorylated three-carbon compounds with high
phosphoryl-transfer potential
○ Hexokinase: catalyzes the transfer of the phosphoryl group from ATP to the
hydroxyl group on carbon 6 of glucose
○ Kinases: enzymes that catalyze the transfer of a phosphoryl group from ATP
to an acceptor
○ Hexokinase (+ other kinases) requires Mg2+ for activity
● Isomerization of glucose 6-phosphate to fructose 6-phosphate
○ Open chain glucose has an aldehyde group at carbon 1 → open-chain
fructose has a keta group at carbon 2
○ The isomerization of glucose 6-phosphate to fructose 6- phosphate is a
conversion of an aldose into a ketose
○ Catalyzed by phosphoglucose isomerase
○ Only three-carbon molecules are metabolized in the later stages of glycolysis
● Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6-biphosphate
○ Catalyzed by phosphofructokinase (PFK)
● Glycolysis: t he sequence of reactions that converts one molecule of glucose into two
of pyruvate while generating ATP
○ Major functions
■ Generating ATP
■ Provide building blocks for biosynthesis
● Gluconeogenesis: process to synthesize glucose
Chapter 16 - Glycolysis
● Why is glucose such a prominent fuel?
○ It’s one of several monosaccharides formed from formaldehyde under
prebiotic conditions → available as a fuel source for primitive biochemical
systems
○ It’s the most stable hexose because the hydroxyl groups and the
hydroxymethyl group are all in the equatorial position → minimizes steric
clashes
○ It has a low tendency to nonenzymatically glycosylate proteins
16.1 - Glycolysis Is an Energy-Conversion Pathway
● Eukaryotic cells → glycolysis takes place in the cytoplasm
● Glucose → 2 pyruvate + 2 ATP
● Enzymes of glycolysis are organized into complexes
○ eg. in yeast → glycolytic enzymes are associated with
the mitochondria
○ eg. in mammalian erythrocytes (red blood cells) →
glycolytic enzymes are found bound to the inner
surface of the cell membrane
○ Arrangement increases enzyme efficiency by
facilitating the movement of substrates and products
between enzymes (substrate channeling) and
prevents the release of any toxic intermediates
● Glycolysis → 2 stages
○ Stage 1: trapping and preparation
■ No ATP is generated
■ Conversion of glucose into fructose
1,6-biphosphate
● Phosphorylation → Isomerization →
phosphorylation
■ Cleavage of the fructose 1,6-biphosphate into
2 phosphorylated three-carbon fragments
○ Stage 2
■ ATP is harvested when three-carbon
fragments are oxidized to pyruvate
, ● Glucose enters the cell through specific transport proteins and has one principal fate
○ It is phosphorylated by ATP to form glucose 6-phosphate
○ Notable because:
■ Glucose 6-phosphate cannot pass through the membrane to the
extracellular side, because it is not substrate for the glucose
transporters
■ The addition of the phosphoryl group facilitates the metabolism of
glucose to the phosphorylated three-carbon compounds with high
phosphoryl-transfer potential
○ Hexokinase: catalyzes the transfer of the phosphoryl group from ATP to the
hydroxyl group on carbon 6 of glucose
○ Kinases: enzymes that catalyze the transfer of a phosphoryl group from ATP
to an acceptor
○ Hexokinase (+ other kinases) requires Mg2+ for activity
● Isomerization of glucose 6-phosphate to fructose 6-phosphate
○ Open chain glucose has an aldehyde group at carbon 1 → open-chain
fructose has a keta group at carbon 2
○ The isomerization of glucose 6-phosphate to fructose 6- phosphate is a
conversion of an aldose into a ketose
○ Catalyzed by phosphoglucose isomerase
○ Only three-carbon molecules are metabolized in the later stages of glycolysis
● Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6-biphosphate
○ Catalyzed by phosphofructokinase (PFK)
