Starvation: Metabolic Changes

Malcolm Watford, Rutgers University, New Brunswick, New Jersey, USA

Published online: April 2015

DOI: 10.1002/9780470015902.a0000642.pub2

Abstract

Animals, including humans, invoke a comprehensive programme of hormonal and metabolic adaptations that enable them to withstand prolonged periods of starvation. The brain is only capable of using glucose or ketone bodies as respiratory fuel. During prolonged starvation, the primary source of glucose is gluconeogenesis from amino acids arising from muscle proteolysis. To spare glucose use (and thus spare muscle protein) most tissues of the body utilise fat‐derived fuels (fatty acid and ketone bodies). As starvation progresses ketone bodies also become the major fuel of the brain, again reducing the need for glucose. High concentrations of ketone bodies result in significant ketonuria with ketones excreted as ammonium salts. The ammonia is derived from the catabolism of glutamine in the kidney with the carbon skeleton being recovered as glucose. This well‐orchestrated pattern of metabolism allows a consistent fuel supply to the brain and other tissues during prolonged starvation.

Key Concepts

  • Circulating glucose concentrations do not drop below 3.5 mmol L−1 even in prolonged starvation.
  • During starvation, the brain must be supplied with fuel in the form of glucose or ketone bodies.
  • Carbohydrate reserves are depleted after 24 h of starvation.
  • In prolonged starvation, gluconeogenesis provides the glucose oxidised by the brain.
  • The major substrates for gluconeogenesis are amino acids derived from skeletal muscle protein breakdown.
  • Circulating ketone body concentrations rise during prolonged starvation.
  • During starvation, most tissues utilise fatty acids and/or ketone bodies to spare glucose for the brain.
  • Glucose utilisation by the brain is decreased during prolonged starvation as the brain utilises ketone bodies as the major fuel.
  • High concentrations of ketone bodies result in significant excretion of ketones.
  • Urinary ketones are excreted as ammonium salts derived from the renal metabolism of glutamine with the carbon skeleton being recovered through renal gluconeogenesis.

Keywords: glucose; fatty acids; ketones; brain metabolism; insulin; amino acids

Figure 1. Origin of blood glucose and rates of whole body glucose utilisation during the five phases of glucose homeostasis.
Figure 2. Plasma fuel concentrations during prolonged starvation.
Figure 3. Interorgan fuel metabolism during prolonged starvation.
Figure 4. Daily urinary nitrogen excretion in a male subject who fasted for 38 days.
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References

Brownsey RW, Boone AN, Elliott JE, Kulpa JE and Lee WM (2006) Regulation of acetyl‐CoA carboxylase. Biochemical Society Transactions 34: 223–227.

Benedict FG (1915) A Study of Prolonged Fasting. Washington: Carnegie Institute.

Cahill GF Jr (1970) Starvation in man. New England Journal of Medicine 282: 668–675.

Cahill GF Jr (2006) Fuel metabolism in starvation. Annual Review of Nutrition 26: 1–22.

Cheryl Y and LeMaho Y (1985) Five months of fasting in king penguin chicks: body mass loss and fuel metabolism. American Journal of Physiology 249: R387–R392.

Elia M, Stubbs RJ and Henry CJ (1999) Differences in fat, carbohydrate and protein metabolism between lean and obese subjects undergoing total starvation. Obesity Research 7: 597–604.

Felig P, Owen OE, Wahren J and Cahill GF Jr (1969) Amino acid metabolism during starvation. Journal of Clinical Investigation 48: 584–594.

Felig P (1973) Amino acid metabolism in man. Annual Review of Biochemistry 44: 933–955.

Fery F and Balasse EO (1980) Differential effects of sodium acetate and acetoacetic acid infusions on alanine and glutamine metabolism in man. Journal of Clinical Investigation 66: 232–331.

Flatt JP (1972) On the maximal possible rate of ketogenesis. Diabetes 21: 50–53.

Hannaford MC, Leites LA, Josse RG, Goldstein MB and Halperin ML (1982) Protein wasting due to acidosis of prolonged fasting. American Journal of Physiology 243: E251–E256.

Harris RA, Bowker‐Kinley MM, Huang B and Wu P (2002) Regulation of the activity of the pyruvate dehydrogenase complex. Advances in Enzyme Regulation 42: 249–259.

Joeung NH and Harris RA (2010) Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels. Korean Diabetes Journal 34: 274–283.

Jungas RL, Halperin ML and Brosnan JT (1992) Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiological Reviews 72: 419–448.

Lass A, Zimmerman R, Oberer M and Zechner R (2011) Lipolysis – a highly regulated multi‐enzyme complex mediates the catabolism of cellular fat stores. Progress in Lipid Research 50: 14–27.

Marliss EB, Aoki TT, Pozefsky T, Most AS and Cahill GF Jr (1971) Muscle and splanchnic glutamine and glutamate metabolism in postabsorptive and starved man. Journal of Clinical Investigation 50: 814–817.

Owen OE, Morgan AP, Kemp HG, et al. (1967) Brain metabolism during fasting. Journal of Clinical Investigation 46: 1589–1595.

Owen OE, Felig P, Morgan AP, Wahren J and Cahill GF Jr (1969) Liver and kidney metabolism during prolonged starvation. Journal of Clinical Investigation 48: 574–583.

Owen OE and Reichard GA (1971) Human forearm metabolism during progressive starvation. Journal of Clinical Investigation 50: 1536–1545.

Owen OE (1989) Starvation. In: de Groot LJ, (ed). Endocrinology. Vol. 3, pp. 2282–2293. Philadelphia: WB Saunders.

Randle PJ, Garland PB, Hales CN and Newsholme EA (1963) The glucose‐fatty acid cycle. It's role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 281: 785–789.

Ruderman NB, Aoki TT and Cahill GF Jr (1976) Gluconeogenesis and its disorders in man. In: Hanson RW and Mehlman MA, (eds). Gluconeogenesis: Its Regulation in Mammalian Species, pp. 515–532. New York: John Wiley.

Ruderman NB, Saha AK, Vavvas D and Witters LA (1999) Malonyl‐CoA, fuel sensing, and insulin resistance. American Journal of Physiology 276: E1–E18.

Saggerson ED (2008) Malonyl‐CoA, a key signaling molecule in mammalian cells. Annual Review of Nutrition 28: 253–272.

Sapir DG and Owen OE (1975) Renal conservation of ketone bodies during starvation. Metabolism 24: 23–33.

Watford M (1994) Glutamine metabolism in rat small intestine: synthesis of three‐carbon products in isolated enteroyctes. Biochimica Biophysica Acta 1200: 73–78.

Zechner R, Zimmerman R, Eichmann TO, et al. (2012) Fat signals – lipases and lipolsis in lipid metabolism and signalling. Cell Metabolism 15: 279–291.

Further Reading

Benedict FG (1915) A Study of Prolonged Fasting. Washington: Carnegie Institute.

Cahill GF Jr (1970) Starvation in man. New England Journal of Medicine 282: 668–675.

Cahill GF Jr (2006) Fuel metabolism in starvation. Annual Review of Nutrition 26: 1–22.

Keys A, Brozek J, Henschel A, Mickelsen O and Taylor HL (1950) The Biology of Human Starvation. Minneapolis: University of Minnesota Press.

Ruderman NB, Aoki TT and Cahill GF Jr (1976) Gluconeogenesis and its disorders in man. In: Hanson RW and Mehlman MA, (eds). Gluconeogenesis: Its Regulation in Mammalian Species, pp. 515–532. New York: John Wiley.

Wahren J and Ekberg K (2007) Splanchnic Regulation of Glucose Production. Annual Review of Nutrition 27: 329–345.

Winick M (1979) Hunger Disease: Studies by the Jewish Physicians in the Warsaw Ghetto. New York: John Wiley.

Related Sub-Topics:

Proteins: Structure, Function, Metabolism | Other Biomolecules: Structure, Function, Metabolism | Lipids: Structure, Function, Metabolism | Bioenergetics
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Article Title: Starvation: Metabolic Changes
 
How to Cite close
Watford, Malcolm(Apr 2015) Starvation: Metabolic Changes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000642.pub2]