David L. Nelson and Michael M. Cox
Lehninger Principles of
Biochemistry
Fourth Edition
Chapter 23:
Hormonal Regulation and Integration of
Mammalian Metabolism
Copyright © 2004 by W. H. Freeman & Company
Chapter Outline
• Learn the diverse structures and
functions of hormones
• Learn how different tissues divide
labor
• Learn how hormones regulate fuel
metabolism
• Learn how our body regulate body
mass
The diverse structures and
functions of hormones
The way hormone get to their target
tissues
• Endocrine: blood
• Paracrine: diffusion through extracellular
space
• Autocrine: no
Major classes of hormones (p. 886,
table 23-1)
•
•
•
•
•
•
•
•
Peptide hormone – glucacon, insulin, TSH
Catecholamine - epinephrine
Eicosanoids - prostaglandin
Steroid - cortisol
Calcitriol
Retinoid – retinoic acid
Thyroid
Nitric oxide
TSH (thyrotropin-releasing hormone)
Insulin are highly concentrated in
secretory vesicles
Catecholamines are highly
concentrated in secretory vesicles
http://images.google.com.tw/imgres?imgurl=http://courses.cm.utexas.edu/lmahal/ch310n/fall2005/Epinephrine.png&imgrefurl=http://courses.cm.utexas.edu/lmahal/ch310n/fall2005/MOTD-8.31.05.htm&h=170&w=408&sz=9&hl=zh-TW&start=2&um=1&tbnid=jouiES_HkdmRhM:&tbnh=52&tbnw=125&prev=/images%3Fq%3Depinephrine%26svnum%3D10%26um%3D1%26complete%3D1%26hl%3Dzh-TW%26sa%3DN
Eicosanoids are produced when
needed
Prostaglandin E1
http://content.answers.com/main/content/wp/en/8/8f/Prostaglandin_E1.png
They are paracrines.
Steroids act through nuclear
receptors
Vit. D activates an intestinal Ca2+
binding protein
http://home.caregroup.org/clinical/altmed/interactions/Images/Nutrients/vitD2.gif
RA regulates growth and
differentiation by nuclear retinoid
receptors
http://www.cyberlipid.org/images/pict42.gif
Thyroid hormones act through
nuclear receptors
NO is synthesized from arginine
• Arginine + 1½NADPH + 2O2  NO +
citrulline + 2H2O +1½NADP+
• This reaction is catalyzed by NO synthase,
which is found in many tissues and cell
types.
How different tissues divide
labor
Sugar
metabolism
in Liver
Between meals or
prolonged fast
Glucose-alanine cycle
Amino acid
metabolism
in liver
Phospholipids, TG
Adipose
tissue
(bound to serum albumin)
Heart & smooth muscle
excess
Membrane
synthesis
Citric
acid
cycle
Fatty acid
metabolism
in liver
Adipose tissues
• Adipose tissue typically makes up
about 15% of the mass of young
adult human, with approximately 65%
of this mass in the form of
triacylglycerols.
Adipose tissue
glucose
pyruvate
Acetyl-CoA
Fatty acids
TAG
lipase
FA
FA
epinephrine
insulin
[ATP]
Slow-twitch and Fast-twitch muscle
• Slow-twitch (red) muscle: rich in
mitochondria, very dense networks of blood
vessels; low tension but highly resistant to
fatigue
• Fast-twitch (white) muscle: fewer
mitochondria, less blood vessels; greater
tension but quicker to fatigue
• The ratio of red/white muscle in any
individual is genetically controlled.
Muscle
10-30 mM
Creatinine kinase reaction
Muscleliver
cooperation
3
Glycogen  G 6-P
 pyruvate
Spend one less ATP
Heart muscle
• Half of the volume of heart muscle is
consisted of mitochondria.
• Fuel: free FA, glucose and ketone bodies

 (blood glucose)
gluconeogenesis
muscle protein
(b-hydroxybutyrate)
Brain
How hormones regulate fuel
metabolism
Insulin
secretion in
pancreas
The well-fed state
glycogen
[Glucose]blood
Activate
-glycogen
phosphorylase
-gluconeogenesis
(FPBase-1, PEP
carboxykinase)
Inactivate
-glycogen synthase
-glycolysis (PFK-1,
pyruvate kinase)
The fasting state
Epinephrine : a stress hormone
Cortisol : another stress hormone
• Cortisol alters metabolism by changing the kinds
and amounts of certain enzymes synthesized in its
target cell.
• Cortisol restore blood glucose level and increase
glycogen stores
• Cortisol
– Increase adipose tissue fatty acids release from stored
TAGs
– Increase muscle protein breakdown and export of
amino acids
– Increase liver gluconeogenesis by stimulating PEP
carboxykinase synthesis
Diabetes mellitus
• Diabetic patients cannot take up glucose
efficiently from the blood (GLUT4)
• Excessive and incomplete oxidation of fatty
acid in the liver
• Acetyl-CoA cannot be completely oxidized
by citric acid cycle because of high
[NADH]/[NAD+] levels, and accumulation
of acetyl-CoA leads to overproduction of
ketone bodies.
Acetone is produced spontaneously
by ketone bodies in diabetic patients
• The odor of acetone is often mistaken as
alcohol.
• Ketone bodies will overwhelm the capacity
of blood’s bicarbonate buffering system 
ketoacidosis.
Obesity and the regulation of
body mass
The Lipostat theory
• A feedback signal
originating in adipose
tissue influencs the
brain centers that
control eating
behavior and activity.
• Leptin (produced by
adipocyte) and leptin
receptors (arcuate
nucleus of the
hypothalamus).
Lack of leptin make mice in a
constant state of starvation
Arcuate nucleus
fat-STATs (STATs 3,5,6)