lehninger principles of biochemistry fourth edition chapter 23: hormonal regulation and integration...
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Lehninger Principles of Biochemistry
Fourth Edition
Chapter 23:Hormonal Regulation and Integration of
Mammalian Metabolism
Copyright © 2004 by W. H. Freeman & Company
David L. Nelson and Michael M. Cox
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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
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The diverse structures and functions of hormones
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The way hormone get to their target tissues
• Endocrine: blood
• Paracrine: diffusion through extracellular space
• Autocrine: no
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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
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TSH (thyrotropin-releasing hormone)
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Insulin are highly concentrated in secretory vesicles
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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
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Eicosanoids are produced when needed
Prostaglandin E1
http://content.answers.com/main/content/wp/en/8/8f/Prostaglandin_E1.png
They are paracrines.
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Steroids act through nuclear receptors
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Vit. D activates an intestinal Ca2+ binding protein
http://home.caregroup.org/clinical/altmed/interactions/Images/Nutrients/vitD2.gif
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RA regulates growth and differentiation by nuclear retinoid
receptors
http://www.cyberlipid.org/images/pict42.gif
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Thyroid hormones act through nuclear receptors
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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.
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How different tissues divide labor
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Sugar metabolism
in Liver
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Amino acid metabolism
in liver
Glucose-alanine cycle
Between meals or prolonged fast
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Fatty acid metabolism
in liver
excess
Phospholipids, TGAdipose tissue
(bound to serum albumin)
Heart & smooth muscle
Citric acid cycleMembrane
synthesis
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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.
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glucose
pyruvate
Acetyl-CoA
Fatty acids
TAG[ATP]lipase
FAFAFA
epinephrine
insulin
Adipose tissue
FA
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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.
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Muscle
10-30 mM
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Creatinine kinase reaction
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3
Glycogen G 6-P pyruvateSpend one less ATP
Muscle-liver
cooperation
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Heart muscle
• Half of the volume of heart muscle is consisted of mitochondria.
• Fuel: free FA, glucose and ketone bodies
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(blood glucose)
Brain(-hydroxybutyrate)
muscle protein
gluconeogenesis
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How hormones regulate fuel metabolism
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Insulin secretion in
pancreas
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glycogen
The well-fed state
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The fasting state[Glucose]blood
Activate-glycogen phosphorylase-gluconeogenesis (FPBase-1, PEP carboxykinase)Inactivate-glycogen synthase-glycolysis (PFK-1, pyruvate kinase)
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Epinephrine : a stress hormone
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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
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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.
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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.
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Obesity and the regulation of body mass
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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).
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Lack of leptin make mice in a constant state of starvation
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Arcuate nucleus
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fat-STATs (STATs 3,5,6)
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