Energy Reserves

 Liver/muscle glycogen are sufficient for brief period (<24hr) of fasting – mostly used for emergencies
(vigorous exercise)
o Liver can release glucose into blood via Glucose-6-Pase; Muscle must consume its own glycogen
 Muscle protein is another possible source but is unfavorable since you would in effect digest your
muscles
 Adipose TG’s provide the major storage form of readily-available energy – provides FFA’s to liver which
makes ketones that are necessary for prolonged starvation
 Fuel homeostasis principally regulates the needs of brain and muscle (major consumers of fuel)
o brain – glucose exclusively (120g/d) until prolonged starvation (~2 days) then switches to ketones
(fuel sparing)

Metabolic Changes during Starvation

 Mechanisms of Protein Conservation
o Muscle protein breakdown during starvation provides liver (for gluconeogenesis) and kidney (for
ammoniagenesis)
o During 1st days of starvation, amino acids (Ala, Gln) are synthesized and released from muscle
 Ala goes to liver for gluconeogenesis
 Gln goes to kidney for ammoniagenesis (also yields glucose); or goes to gut and
converted to Ala which goes to liver
o As starvation progresses, ammoniagenesis required to maintain acid-base homeostasis rises in
kidney (due to increased FFA’s and circulating ketones) which secondarily yields more glucose
thus kidney becomes major source of gluconeogen
 By 3 days starvation, brain begins utilizing ketones and skeletal muscle relies on ketones
for 50% of its energy
 The switch from glucose to ketone usage aids in reducing the rate of muscle protein
degradation needed for gluconeogenesis – if this did not occur, the body would lose >½ of
its muscle protein within 17 days leading to death
 By 24 days starvation, ketone synthesis, nitrogen excretion, and gluconeogen (from
lactate, glycerol, Gln) reach a steady state allowing starvation to persist for 2 – 3 months
 Ketone Body Metabolism
o Increased availability of FFA’s during starvation provides liver with increased levels of acetyl CoA
and eventually exceeds the oxidative capacity of the liver, thus acetyl CoA is shifted from the TCA
cycle towards ketone synthesis
o Acetyl CoA is made into HMG-CoA via HMG-CoA Synthase (rate-limiting enzyme – only found in
liver); HMG-CoA is then made into acetoacetate, b-hydroxybutyrate, and acetone (minor) and
released into blood since liver cannot utilize them
o Ketones are used by skeletal and cardiac muscle, the renal cortex, and other tissues (brain only
uses during starvation)
 Role of the Kidney
o Kidney, like liver, possesses the complete enzymatic apparatus for gluconeogenesis
o During brief periods of starvation, kidney’s rate of gluconeogenesis is 10% to that of the liver
o During prolonged starvation, ammoniagenesis increases due to increased acid load which
accelerates its rate of gluconeo
o The principle gluconeogenic substrate is Gln which also provides the free NH 3 (used to titrate
excess H+ ions)
 Hormonal Control During Starvation
o Insulin levels decrease (aids FA mobilization, gluconeogenesis and ketone production)
o Growth hormone increases (stimulates lypolysis) with a reduction in thyroid hormone (major
energy conserving adaptation by decreasing basal metabolic rate and limiting muscle protein
breakdown)
o Glucagon (stimulates gluconeogenesis)

 , then returns to postabsorptive levels concurrent with reduced glucose demand