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)