Glycolysis

Glycolysis
Definition(s)
• Glycolysis means "splitting sugars." Glucose, a six carbon sugar, is split into two molecules
of a three carbon sugar. In the process, two molecules of ATP, two molecules of pyruvic
acid and two "high energy" electron carrying molecules of NADH are produced.
• A set of enzymatic reactions that breakdown 6-carbon glucose to two 3-carbon pyruvate
molecules with generation of energy
• An ATP-generating metabolic process that occurs in nearly all living cells in which 6-C
glucose is converted in a series of steps to 3 C-pyruvate.
• The metabolic breakdown of glucose and other sugars that releases energy in the form of
ATP.
• etc
1
Biomedical Importance of Glycolysis
• Most tissues have at least some requirement for glucose.
• In brain, the requirement is substantial.
• Glycolysis, the major pathway for glucose metabolism, occurs in the cytosol of all
cells.
• It is unique in that it can function either aerobically or anaerobically.
• In the presence of oxygen, glycolysis is the first stage of cellular respiration.
Without oxygen, glycolysis allows cells to make small amounts of ATP. This
process is called fermentation.
• Erythrocytes, which lack mitochondria, are completely reliant on glucose as their
metabolic fuel and metabolize it by anaerobic glycolysis.
• In addition some of the intermediates formed as a result of glycolysis are
important building blocks for other complex molecules.
2
• From glucose to pyruvate there are 10 enzymatic steps
• The first 5 steps constitute the preparatory phase when energy in the form of 2
ATP molecules is spent per glucose molecule.
• The last 5 steps constitute the payoff phase where the energy generated is used
to form 4 ATP molecules on one carrier of high potential electrons i.e. NADH per
glucose molecule.
• Therefore glycolysis of a glucose molecule leads to a net gain of 2 ATP molecules
within the cytosol.
3
4
• There are 3 irreversible reactions
– The first reaction catalyzed by hexokinase/glucokinase
– The third reaction catalyzed by phosphofructokinase-1
– The tenth reaction catalyzed by pyruvate kinase
• The third reaction catalyzed by phosphofructokinase -1 is the most important control
point in glycolysis.
• The only oxidation in glycolysis is catalyzed by glyceraldehyde 3-phosphate
dehydrogenase which forms 1,3-bisphosphoglycerate from glyceraldehyde 3-
phosphate
– Electrons are collected by NADH + H+
• Two molecules of glyceraldehyde 3-phosphate are formed from one molecule of
glucose during glycolysis.
• Therefore from glyceraldehyde 3-phosphate to pyruvate there are 2 sets of identical
reaction.
5
• ATP is formed at 2 points on each arm of the two sets of reactions from glyceraldehyde 3-
phosphate
1. When 1,3-bisphosphoglycerate is converted to 3 phosphoglycerate (Catalyzed by
phosphoglycerate kinase)
2. When phosphoenolpyruvate is converted to pyruvate (Catalyzed by pyruvate kinase)
• In the presence of oxygen
– Pyruvate enters the mitochondria for further oxidation
– The electron carrier NADH + H+ is oxidized to NAD+.
– The formed NAD+ becomes available to support oxidation of glyceraldehyde 3-phosphate
• In the absence of oxygen
– Pyruvate does not enter the mitochondria for further oxidation
– The electron carrier NADH + H+ is not oxidized to NAD+.
– Because no NAD+ is regenerated to support oxidation of glyceraldehyde 3-phosphate glycolysis can
not be sustained
– The only way to regenerate oxidized NAD+ to support glycolysis under anaerobic conditions is to
reduce pyruvate to lactate
6
• Formation of lactate from pyruvate (lactate fermentation) is
the only way glycolysis can be sustained under anaerobic in
vigorously contracting muscles to generate energy.
• Red blood cells without mitochondria also rely mainly on
anaerobic glycolysis as a source of energy
• Monosaccharides like mannose, galactose and fructose can
also like link-up with glycolysis at various points.
7
Fermentation
- starts with glycolysis
- does not make ATP but allows
glycolysis to continue)
Overview of Respiration
Organic Compounds
Glycolysis
Oxygen Present Oxygen Absent
Cellular Respiration Fermentation

(aerobic) (anaerobic)
Fermentation (cont)
Types
1) Lactic Acid Fermentation
- occurs in your muscle cells
- produces lactic acid, results in muscle
fatigue and cramps
- produces NAD+ that goes back to glycolysis
Lactic Acid Fermentation
Fermentation (cont)
2) Alcoholic Fermentation
- produces alcohol (ethyl) and carbon dioxide
- produces NAD+ that goes back to glycolysis
Alcoholic Fermentation
Importance of Fermentation
- produces food products we use
(bread, cheese, yogurt)
- allows glycolysis to continue
-
Rate of glycolysis is regulated to meet two requirements
– Degradation of glucose for ATP generation
– Provides building blocks for synthetic reactions like formation of long-chain
fatty acids
• Control is at irreversible reactions
• The enzyme which controls the most important step phosphofructokinase 1
– Is inhibited by
• High ATP
• Drop in pH
• High citrate concentration
– Is activated by high ADP, high AMP and fructose 2,6-bisphosphate
• Hexokinase (muscle, CNS, etc) is inhibited by glucose 6-phosphate
• Glucokinase (liver)is not inhibited by glucose 6-phosphate
16
1. In which cellular component does glycolysis occur?
2. How many enzymatic steps are there from glucose to to pyruvate in
glycolysis?
3. Which are the two high energy intermediates formed in glycolysis?
4. Which enzymes catalyze irreversible steps in glycolysis?
5. The most important control step in glycolysis is catalyzed by which enzyme?
6. Why does lactate form in strenuously exercising skeletal muscles?
7. Give an example of cells which rely almost entirely on glucose as a source of
energy.
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Glycolysis

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Cellular Respiration Fermentation

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