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Chapter 23, Hormonal Regulation and Integration of Mammalian Metabolism

. 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. Metabolismof sugars in Liver.. Glucokinase (Km =10mM). (4 mM). Occurs when the carbohydrateintake is in excess..

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Chapter 23, Hormonal Regulation and Integration of Mammalian Metabolism

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    1. 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.

    12. Metabolism is regulated at different levels At the level of the individual cells: Regulation of enzyme activities by substrate availability, allosteric mechanisms, covalent modifications. At the level of the whole organism: Chemical messengers of the neuroendocrine system, neurotransmitters and hormones.

    14. Fuel metabolism of different organs is coordinated through various hormones 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).

    17. 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.

    19. Hormones are chemical messengers secreted by certain tissues into the blood or institial fluid, serving to regulate the activity of other tissues.

    20. 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).

    22. Radioimmunoassya (RIA) was an extremely sensitive quantitative method developed to assay peptide hormones (Yalow, 1970s) Antibodies binding to a hormone specifically and with high affinity are used. A constant amount of antibody is incubated with a fixed amount of radioactively labeled hormone. Unlabeled hormone in samples will compete with the labeled ones to bind to the antibodies.

    26. Peptide hormones are usually generated as larger precursors.

    32. The adipose tissue was found to produce a protein hormone, leptin, that act on the hypothalamus to regulate the feeding behavior and energy expenditure of a mammal to maintain a constant body mass (homeostasis).

    34. Summary Each organ/tissue in a mammal has specialized roles in metabolism. Liver has remarkable metabolic flexibility and works for other tissues in providing appropriate fuels. The working of all organs/tissues is highly coordinated/integrated via the hormones, a group of chemically diverse molecules.

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