Lehninger Principles of Biochemistry Fourth Edition Chapter 23: Hormonal Regulation and Integration...
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Transcript of Lehninger Principles of Biochemistry Fourth Edition Chapter 23: Hormonal Regulation and Integration...
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
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
Amino acid metabolism
in liver
Glucose-alanine cycle
Between meals or prolonged fast
Fatty acid metabolism
in liver
excess
Phospholipids, TGAdipose tissue
(bound to serum albumin)
Heart & smooth muscle
Citric acid cycleMembrane
synthesis
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.
glucose
pyruvate
Acetyl-CoA
Fatty acids
TAG[ATP]lipase
FAFAFA
epinephrine
insulin
Adipose tissue
FA
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
3
Glycogen G 6-P pyruvateSpend one less ATP
Muscle-liver
cooperation
Heart muscle
• Half of the volume of heart muscle is consisted of mitochondria.
• Fuel: free FA, glucose and ketone bodies
(blood glucose)
Brain(-hydroxybutyrate)
muscle protein
gluconeogenesis
How hormones regulate fuel metabolism
Insulin secretion in
pancreas
glycogen
The well-fed state
The fasting state[Glucose]blood
Activate-glycogen phosphorylase-gluconeogenesis (FPBase-1, PEP carboxykinase)Inactivate-glycogen synthase-glycolysis (PFK-1, pyruvate kinase)
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)