Professional Documents
Culture Documents
• Introduction
• Basic mechanisms – intersections of pathways
• Physiological questions
• Major sites of regulation
• Regulation in liver
• Regulation in cardiac muscle
• Alcohol metabolism
• Pathways
• Clinical correlations
• Clinical scenario: Chronic alcohol consumption
All images are from “Marks et al., 2nd Edition, Copyright © 2005 Lippincott &
Williams, A Wolters Kluwer Co., All rights reserved” unless otherwise noted.
• Catabolic reactions:
•Source of ATP
• Anabolic reactions:
Complex Glycolysis •Pyruvate is precursor for
carbohydrates fatty acid biosynthesis
NADPH
and alanine
ATP •Pentose phosphates
precursor of nucleotides.
TCA Cycle
Figure 2 of the Section Five Introduction, Mark’s et al.
Major pathways of glucose metabolism
(storage)
Glucose-6-P
Complex Glycolysis
carbohydrates NADPH
ATP
TCA Cycle
Figure 2 of the Section Five Introduction, Mark’s et al.
Glucose
Anaerobic
Glycolysis
Lactate
Alternate fates of pyruvate
Glucose + 2 ADP + 2 Pi →
2 Lacate + 2 ATP + 2 H2O + 2 H+
Fig. 22.8: Malate - aspartate shuttle Fig. 22.7: Glycerol 3-phosphate shuttle
Review of Unit 4…
Product inhibition
Pi
Glucose 6-
phosphatase
• Allosteric regulation
of PFK-1 by AMP to
a lower Km (higher
affinity) +AMP
Regulation of Rest
glycolysis in ~ 20%
Exercise
cardiac muscle
by AMP
adenylate
kinase
2 ADP ←⎯⎯→ AMP + ATP
~ 300%
• Allosteric regulation of
PFK-1 by F2,6-BP to
a lower Km (higher
affinity)
• F2,6-BP is more
effective activator of
PFK-1, mole for mole,
than AMP
PFK-2
has both
of these
activities
↑ cAMP
Higher PFK-2
Higher PFK-2
phosphatase
kinase activity
activity
results in results in less
more F 2,6-BP F 2,6-BP
Activation of glycolysis by Fructose 2,6-Bisphosphate
Liver
PFK-2
Liver phosphoryation favors phosphatase activity
Cardiac
Muscle
PFK-2 Muscle phosphoryation favors kinase activity
Liver:
Pyruvate kinase
Alcohol (Ethanol) is a fuel
(Toxic)
Fig. 25.1
Aldehyde dehydrogenase
(Mitochondrial enzyme)
(Nontoxic)
Fig. 25.2
Alcohol metabolism
TCA cycle
Fatty Acid Synthesis
Clinical scenario: Metabolic effects of
chronic ethanol consumption
• Summary of metabolic pathways
• Ethanol is both lipid and water soluble and thus is
readily absorbed by passive diffusion
• Ethanol is principally metabolized in the liver with as
many as 13 ATP synthesized per molecule
• Products are acetaldehyde, acetate and acetyl CoA
• Acetyl CoA →TCA cycle or fatty acid synthesis in the liver
• Acetaldehyde is toxic
• Reducing equivalent NADH and H+ produced
• Nutritional Effects
• Chronic alcohol consumption results in decreased
adsorption of vitamins B1 (thiamin) and B12
• Behavioral Effects – (Acetaldehyde)
Nutritional effects?
?
Source: Carlsberg brewery website
• The enzymes of alcohol metabolism are
a family of isozymes
• Variation in the isozyme proportions affects
• rate of alcohol clearance,
• degree of inebriation,
• side effects of alcohol consumption and
• susceptibility to alcohol-induced liver disease
• Points 2 – 4 are directly related to the
concentration of the acetaldehyde
intermediate