北大生化课件chapter23

The Nobel Prize in Physiology or Medicine 1923
"for the discovery of insulin"
Frederick Grant Banting b. 1891 d. 1941
John James Richard Macleod b. 1876 (in Cluny, Scotland) d. 1935
and with high affinity are used. A constant amount of antibody is incubated with a fixed amount of radioactively labeled hormone. hormone. Unlabeled hormone in samples will compete with the labeled ones to bind to the antibodies.
•
Coordination of metabolism in separate organs is achieved by the neuroendocrine system.
Over short distance
Over long distance
Fuel metabolism of different organs is coordinated through various hormones
Metabolism of sugars in Liver.
GLUT2 Glucokinase (Km =10mM)
Blood Glc (4 mM)
(then transported to other tissues)
Occurs when the carbohydrate intake is in excess.
Active fatty acid mobilization Active synthesis of ketone bodies.
Active protein degradation.
Fuel metabolism in liver during prolonged fasting or uncontrolled diabetes mellitus.
Phosphorylated Glc
Muscles lack glucose 6-phosphatase.
Fermentation
Aerobic oxidation
Metabolic cooperation between the skeletal muscle and liver.
The Cori Cycle
• Insulin, glucagon, and epinepherine have
been found to interplay in coordinating fuel metabolism in muscle, liver, and adipose tissue, thus keeping the blood glucose level near 4.5 mM. Insulin signals high blood glucose (acts mainly on liver, muscle and adipose tissues). Glucagon signals low blood glucose (acts mainly on liver and adipose tissues). Epinepherine signals impending activity (acts on muscle, liver and adipose tissues).
– Regulation of enzyme activities by substrate availability, allosteric mechanisms, covalent modifications. At the level of the whole organism: organism: – Chemical messengers of the neuroendocrine system, neurotransmitters and hormones.
Mitochondria make up about half of the volume of the heart Muscle cells.
The heart completely depends on aerobic oxidation to obtain energy, i.e., O2 is absolutely needed for heart to work!
Fatty acids are the preferred fuel for energy production in heptocytes.
Metabolism of amino acids in liver.
Glucose-Alanine cycle smoothes out fluctuations of blood glucose level during meals.
Brain is a major glucose consumer
The most fastidious, one of the most voracious of all the organs! O2 and glucose cannot be interrupted!
Fatty acids do not serve as a fuel!
Each organ has a specialized function: The division of labor.
Issues: which fuels they use, which fuels they generate, how they adjust their metabolism at different physiological conditions
Metabolism of fatty acids in liver.
Excess carbohydrates are converted into lipids in liver and transported to adipose tissue for storage.
Adipose tissue stores and supplies fatty acids
Dr. Zengyi Chang’s Lecture notes for Dec. 26, 2007 (Biochemistry II)
Chapter 23, Hormonal Regulation and Integration of Mammalian Metabolism
★Specialized metabolism of major organs and tissues: the division of labor; ★Coordination of metabolism for different organs via hormones. ★ Responding to changing external conditions. ★ Meeting the demands of growth and reproduction.
Hormones, extremely potent, are often present in extremely low concentrations and a bioassay must be established before their discovery and characterization.
• For instance, insulin was discovered as
a substance affecting the volume and composition of urine produced by a dog (Banting, Macleod and Collip, 1920s).
Activemones are chemical messengers secreted by certain tissues into the blood or institial fluid, serving to regulate the activity of other tissues.
• • •
The well-fed state:
Stimulated by an increase in blood glucose level.
Insulin stimulates glucose consumption and storage in muscle and liver.
Stored as glycogen or triacyglycerol.
Consumes about 120 g glucose daily.
Blood mediates the metabolic interactions among all tissues.
Blood
Metabolism is regulated at different levels
• At the level of the individual cells: cells:
The fasting state:
Glucagon stimulates glucose production and release in liver.
Also mobilizes the fatty acids (sparing glucose for the brain)
In untreated diabetes, insulin is either not produced (Type I or IDDM) or is not recognized by the tissues (Type II or NIDDM), and the uptake of blood glucose is compromised. High level of glucose in blood and urine; production and excretion of ketone bodies.