BIOCHEMISTRY – LECTURE SEVEN
glycolysis and gluconeogenesis
The catabolism of glucose to form 2 molecules of pyruvate occurs in the cytosol
and is anaerobic. 10 steps are involved, most are reversible. The direction these
reactions happen in is dependent on the relative concentration of substrate and
product. There are 3 irreversible steps. It can be looked at in 3 stages:
The double phosphorylation of glucose. This requires an investment of
ATP.
The cleavage of glucose into two 3-carbon molecules. This allows the
subsequent stage.
The conversion of these molecules to pyruvate. This generates energy
molecules and provide pyruvate, from which more energy can be
extracted.
Glycolysis:
1. This first step is catalysed by the enzyme hexokinase and ATP is used. It
provides the phosphate and the energy to drive the reaction. The
phosphorylation of the glucose molecule prevents it from leaving the cell.
This is one of the 3 irreversible steps in glycolysis. Kinase enzymes are
enzymes that catalyse the transfer of phosphate groups between an ATP
molecule and another molecule. In liver cells this reaction is catalysed by
glucokinase. Although the reaction is the same, glucokinase has slightly
different properties that make it perfectly suited to the livers function in
carbohydrate metabolism. Glucokinase has a higher Km than hexokinase
and glucokinase is not inhibited by high concentrations of glucose 6-
phosphate.
2. This step is catalysed by phosphoglucose isomerase, the ring form of
glucose 6-phosphate is converted to the chain form to allow for the
rearrangement of the 5-carbon ring into a 4-carbon ring. There is no
addition or loss from the molecule, just rearrangement. An isomerase
enzyme catalyses the isomerisation of a molecule, the product will have
the same number and type of atoms, but in a different arrangement. In
this case, the carbonyl oxygen is moved from carbon 1 to carbon 2 prior to
the new ring structure being formed.
3. This step is catalysed by phosphofructokinase (PFK), carbon 1 is
phosphorylated. Again, ATP is used to provide the phosphate and the
energy to drive the reaction. The molecule created, fructose 1,6-
bisphosphate, is nearly symmetrical, ready for the next cleavage step to
form two 3 carbon molecules. This is a key control point for glycolysis. Like
most metabolic pathways, glycolysis is controlled by controlling the
activity of one or two key steps. For glycolysis, the pathway is largely
controlled by regulating the activity of PFK. This step is the 2 nd irreversible
step.
4. This step is catalysed by aldolase, the 6-carbon sugar fructose 1,6-
bisphosphate is cleaved to form two similar 3 carbon molecules,
dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Only
glyceraldehyde 3-phosphate progresses on to form pyruvate directly, the
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