Transcript Lecture 9-lea

Dental Biochemistry 2015
Lecture 9 - Glycolysis
Michael Lea
Lecture Outline
•
•
•
•
Function of glycolysis
Metabolic sequence
Rate limiting steps
Distinction between anaerobic and
aerobic glycolysis
Suggested Reading
• Meisenberg and Simmons. Principles of
Medical Biochemistry, 3rd edition,
pages 347-353, 374-379
Function of Glycolysis
• The function of glycolysis is to convert
glucose to three carbon compounds
with the formation of ATP
• Glycolysis occurs in all the cells of the
body and the enzymes are located
mainly in the cytosol.
Metabolic Sequence
• Glycolysis is a sequence of ten
reactions in which glucose is converted
to pyruvate.
• There is an initial requirement for ATP
but glycolysis results in a net production
of ATP.
• There is one oxidative step in which
NAD is reduced to NADH.
Hexokinases
• The phosphorylation of glucose is catalyzed by
hexokinases.
• The predominant hexokinases in most tissues have a
high affinity for glucose and will be saturated at
circulating glucose concentrations
• In liver and pancreatic islets there is a hexokinase
with a high Km value (low affinity). This enzyme is
called glucokinase. Fluctuations in circulating glucose
concentration will affect the velocity of the reaction
catalyzed by glucokinase.
Inhibition of Glycolysis by Fluoride
• Fluoride inhibits the enzyme enolase and thereby
decreases the production of lactic acid by glycolysis.
• Note that fluoride also makes the calcium phosphate
in teeth more resistant to solubilization at low pH.
Rate-limiting Steps
• Regulation is mainly exerted at the 3 essentially
irreversible reactions catalyzed by hexokinase,
phosphofructokinase and pyruvate kinase.
• The most important rate-limiting step is that catalyzed
by phosphofructokinase.
• Phosphofructokinase is inhibited by high
concentrations of ATP.
• Note that the activity of glucose transporters (GLUTs)
can affect the intracellular glucose concentration.
Insulin increases the activity of GLUT4 and this is
particularly important for muscle and adipose tissue.
Distinction between anaerobic and
aerobic glycolysis
• Under anaerobic conditions in
mammalian cells, pyruvate is reduced to
lactate using NADH as the coenzyme.
• Under aerobic conditions, pyruvate is
oxidized to form acetyl coenzyme A
which can be oxidized to yield carbon
dioxide in the citric acid cycle.
Pasteur and Warburg Effects
• The rate of glycolysis is usually greater under
anaerobic conditions than aerobic conditions. The
inhibition of glycolysis by oxygen is known as the
Pasteur effect.
• Cancer cells tend to have high rates of glycolysis and
a decreased Pasteur effect. This common feature of
cancer cells is known as the Warburg effect.
Lecture Objectives
• After studying this lecture material you should be able
to
• Describe where glycolysis occurs
• Explain the importance of glycolysis
• Describe all the reactions of glycolysis particularly the
3 irreversible reactions, the formation of ATP and the
NAD requiring reaction.
• Identify the key regulated step
• Explain the distinction between anaerobic and
aerobic glycolysis