26 April 2009

Biochem of starvation

Humans didn’t always have restaurants and grocery stores to visit on every corner. As part of human evolution, in fact, most of the time it’s likely our ancestors were starving quite often and got pretty good at it while foraging and hunting.

It took the agricultural revolution to really make a shift to food aplenty. But starvation hasn’t gone away by any stretch. It’s a daily reality for much of the underdeveloped world.
And, a bit closer to my reality, my own great grandmother often shared stories with me about how she’d go for weeks without meals as a little girl.

To be able to survive from meal to meal, we depend on a starve-feed cycle. It refers to the changes in metabolism that allows variable fuel and nitrogen consumption to meet variable metabolic and anabolic demand (1). In plain English, it is what gives humans capacity to eat food well beyond caloric requirements and store it as glycogen and triacylglycerol to utilize when needed (1).

This is what happens to someone biochemically as they enter starvation.

Early Starvation State (about two-five days after last meal)

About two days after a last meal with insulin low and glycagon on the rise, glycogen is depleted and muscle proteolysis is predominating (1). The protein catabolism would release of a mix of amino acids high in alanine and glutamine into the blood (1p246).

The alanine stimulates glycogen and is taken up from the liver where it's deaminated for conversion to urea and where pyruvate can be used for gluconeogenesis (1p246). Gluconeogenesis is also made from recycled lactate, pyruvate and from glycerol from fat tissue lipolysis (1p245). Blood glucose levels are successfully kept normal (1p246).

Prolonged Starvation State (one week or longer after last meal)

As starvation becomes prolonged, the body enters a metabolic shift. The shift is away from the glycogen-depleting and muscle-protein-breakdown fasting state (1). The body now intends to conserve vital body proteins to preserve vital functions such as antibodies fighting infection, enzymes catalyzing reactions and hemoglobin transporting oxygen (1).

For energy, the body begins using fat conveniently stored in adipose tissue during a time when more calories were consumed than expended (1). Thus, the blood’s level of fatty acids increases as those fatty acids become fuel (1). The heart, liver and muscle all oxidize them, but not the brain because fatty acids can’t cross the blood-brain barrier (1). The brain can use glycerol backbones, however, and these largely replace amino acids and glucose as its fuel (1).

TCA cycle intermediates for gluconeogenesis eventually become depleted and low levels of oxaloacetate coupled with rapid production of acetyl CoA from fatty acid catabolism create accumulation favoring ketone bodies (1). The ketone bodies are valuable as an energy source for sparing protein (1).

To survive in a starvation state generally depends on stored fat before starvation, although ketosis can cause significant physiological damage and even death (1). The ketosis is kept in check as long as possible by directing glutamine to kidneys, but acidosis increases as ketone production accelerates (1). Once fat stores are used up the body starts on essential protein leading to liver and muscle function loss that ultimately leads to death (1).

Reintroducing Food

As a starved person begins to eat again, there are metabolic interrelationships between the liver, muscle and fat tissue. Triaylglycerol is metabolized normally, but glucose metabolism must be slowly re-established (1). The reason is because the liver extracts glucose poorly and ends up staying in a gluconeogenec mode for awhile after feeding (1).

But the hepatic gluconeogenesis is not producing blood glucose (1). It's providing glucose 6-phosphate for glycogenesis (1). It's an indirect pathway for glycogen synthesis because glucose is catabolized in other tissues (muscle, fat) and then sent to the liver to be converted to the glycogen (1).

Finally, after a few hours, gluconeogenesis declines and glycolysis predominates (1). The liver glycogen then can be sustained again by direct synthesis from blood glucose (1).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.


Johnstone AM. Fasting - the ultimate diet? Obes Rev 2007;8:211-22.
Cahill GF, Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006;26:1-22.

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