Regulation of Metabolism

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Regulation of Metabolism

• The metabolic rate is influenced by physical
  activity, temperature and eating
• When caloric intake is greater than expended
  energy over a period of time, excess calories are
  primarily stored as fat
• Vitamins and metals serve primarily as cofactors
  and coenzymes
• Many water soluble vitamins are needed for the
  activity of enzymes involved in respiration
• The fat soluble vitamins, A and D, have specific
  functions but share similar mechanism of action,
  activating nuclear receptors and regulating
  genetic expression

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Continued

• The body tissues can use glucose, fatty acids,
  ketone bodies, amino acids etc for cell
  respiration
• Different organs have different preferred energy
  sources
• Eating behavior is regulated, at least in part,
  by the hypothalamus
• Lesions of the ventromedial area produce
  hyperphagia whereas lesions of the lateral
  hypothalamus produce hypophagia
• Adipocytes secrete leptin, which regulates food
  intake and metabolism and TNFa which may help to
  regulate the sensitivity of skeletal muscle to
  insulin

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Energy Fuels for Tissues

• Skeletal Muscle Glucose, fatty acid and (ketone
  bodies)
• Cardiac Muscle Fatty acids and (ketone bodies)
• Brain Glucose and (ketone bodies)

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Main Pathways of Metabolism
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Digestion of Proteins, Carbohydrates and Lipids
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Absorption in gastrointestinal tract
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Absorption of Amino Acids
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Glucose homeostasisHow glucose controls insulin
and glucagon release?
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Metabolic Effects of Insulin
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Metabolic Effects of Glucagon
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Counter Regulation of Glycolysis and
Gluconeogenesis
G? G-6-P ?
F-6-P (for gluconeogenesis) F-1,6-Bis Pase
PFK-1 (for Glycolysis)
() F-2,6-BP
F-1,6-BP F-2,6-Bis Phosphate
up-regulates PFK-1 and down regulates
F-1,6-Bpase The concentration of F-2,6-BP is
regulated by a bifunctional enzyme with two
active sites PFK-2_at__at__at__at__at__at__at__at__at__at__at__at__at_F-2,6-BisPase PFK-
2 converts F-6-P to F-2,6-BP and F-2,6-Bpase
converts F-2,6-BP to F-6P.
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Glucagon
Glucagon Receptor
G Protein
Activate Adenylate Cyclase
cAMP
ATP
Activation of protein kinase A
Phosphorylation of double headed enzyme PFK-2

F-2,6-Pase P(inactive)
(active) P
F-2,6-BP
A decrease of F-2,6-BP lowers PFK-1 activity
and increases F-1,6-BPase activity and therefore
more glucose is produced
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For Glycolysis, when glucose enters liver
cells Plasma insulin A
phosphatase is induced and PFK-2-----------------F
-2,6-BisPase is dephosphorylated. Now PFK-2 is
activated and F-2,6-BisPase is inhibited This
increases the concentration of F-2,6-BisP. This
compound activates PFK-1 and this activates
glycolysis. So phosphorylation and
dephosphorylation of double-headed enzyme by
glucagon or insulin controls the amount of
glucose produced or used