Glycolysis and the Citric Acid Cycle

by / Tuesday, 31 August 2010 / Published in Biochemistry


Glycolysis is the process whereby glucose is converted to pyruvate.  Glycolysis consists of ten reactions with FOUR irreversible steps/enzymes.

The Prepatory Phase – Consists of the first five steps, also known as the investment phase.  This phase consumes energy that is used to convert glucose into two 3-C sugar phosphates (G3P).  In this phase, the net ATP is (-2).

The Pay-Off Phase – Consists of five steps that produce a net gain of 2 ATP and 2 NADH molecules (per glucose molecule that goes through the pathway).  Pyruvate is also the end product of the glycolytic pathway.

The total ATP generated from anaerobic glycolysis is 2 ATP’s.  When compared to ATP produced with the malate shuttle and glucose-3-phosphate shuttle, which create 38 ATP’s and 36 ATP’s respectively.


There are FOUR steps in glycolyisis that are considered to be irreversible, thus once they have occurred, glycolysis must progress in the forward direction.  The four regulatory enzymes are:

  1. Hexokinase
  2. Phosphofructokinase
  3. Pyruvate kinase
  4. Pyruvate dehydrogenase


–       Hexokinase is responsible for the first step of glycolysis in the muscles and brain.

–       It is inhibited by the presence of glucose-6-phosphate, which is the product of its activity.

–       This step is important because it prevents the consumption of too much cellular ATP in the formation of glucose–6–phosphate when glucose is not limiting.

–       Hexokinase has a low affinity to glucose, thus it permits glycolysis initiation even if blood glucose levels are low.


–       PFK is the rate-limiting step of glycolysis, thus it is the most important control point throughout the whole process.

–       Regulation is by both alloesteric effectors and by covalent modifications (ie phosphorylation).

–       It is stimulated by the presence of AMP and fructose-2,6-bisphosphate.

–       Even if ATP is high, the presence of AMP can overcome its inhibitory effects due to the ability to allosterically activate PFK.

–       It is inhibited by the presence of ATP and citrate

Pyruvate Kinase:

–       Similar to PFK, is regulated by allosteric effectors and by phosphorylation.

–       PK is activated by fructose-1,6-bisphosphate and inhibited by ATP and alanine.


The citric acid cycle is an essential metabolic process that is essential for completing the oxidative degredation of monosaccharides, fatty acids, and amino acids.

Serves 2 main purpose:

  1. To increase the cell’s ATP producing potential by generating reduced electron carriers such as NADH and reduced ubiquinone. ( QH2).
  2. To provide the cell with precursors that can be used to build a variety of molecules, depending on the cell’s needs.

Under aerobic conditions, the following quantities of ATP are generated:

Glycolysis = 2 ATP (net), 2 NADH (equaling 6 ATP)

Pyruvate to ACoA = 2 NADH = 6ATP

Citric Acid Cycle = 2 GTP (2 ATP), 6 NADH (~ 18 ATP), 2 QH2 (4 ATP)

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