Question

A mountain climber was trapped in a high mountain ravine for five days. During that time she had no food but had plenty of water. She continued to try to find a way out so she was still moving most of the time she was trapped but was not able to find her way out. What is happening biochemically in this person in that fifth day without food?

For one of the following tissues discuss the fuels and pathways in the places in the template as indication.   

a. Skeletal muscle
         i. Fuels being utilized and why these are the major fuels being utilized in this situation (2).

          ii. Pathways of fuel metabolism, both utilization and storage, which are being activated and pathways which are being inhibited under these conditions. Also briefly explain how and why these pathways are being affected by this situation. Be sure your answers include the most highly regulated steps/enzymes of each of these mentioned pathways (show the reactions and enzymes) (5).   

Answer 1

During 5-day starvation, gluconeogenesis would occur as cells would try to make glucose from sources other than non-carbohydrate sources such as amino acids and fats. Thus fatty acid oxidation would occur along with TCA cycle and electron transport chain. Ketone oxidation would also occur.

Glycogen stores last for roughly 24 hours. The liver manufactures new glucose from amino acids in a process called “gluconeogenesis”. The low levels of insulin reached during fasting stimulate lipolysis, the breakdown of fat for energy. The storage form of fat, known as triglycerides, is broken into the glycerol backbone and three fatty acid chains. Glycerol is used for gluconeogenesis. Fatty acids cannot be used by the brain directly. Thus Ketone bodies(beta-hydroxybutyrate and acetoacetate, ), capable of crossing the blood-brain barrier, are produced from fatty acids for use by the brain. After four days of fasting, approximately 75% of the energy used by the brain is provided by ketones. Finally when all the fat stores are depleted the muscle proteins come into action to provide energy.

Fatty acids by themselves cannot be used as a direct fuel source. They must first undergo beta-oxidation in the mitochondria in skeletal muscle, cardiac muscle, and liver cells. Fatty acids are transported into the mitochondria as an acyl-carnitine via the action of the enzyme CAT-1. Ketogenesis converts long-chain fatty acids to short chain fatty acids as they are less hydrophobic and thus can pass easily into brain cells in comparison to long chain fatty acids.  The resulting ketone bodies, acetoacetate and β-hydroxybutyrate, are amphipathic and can be transported into the brain and broken down into acetyl-CoA for use in the TCA cycle. Acetoacetate breaks down spontaneously into acetone, and the acetone is released through the urine and lungs to produce the “acetone breath” that accompanies prolonged fasting.

. Acetoacetate breaks down spontaneously into acetone, and the acetone is released through the urine and lungs to produce the “acetone breath” that accompanies prolonged fasting i.e, in this case, this happens after 5 days. For example, primary gluconeogenic acid alanine comes from muscle proteins.

During starvation, gluconeogenesis is activated hence the enzymes of gluconeogenesis are activated and enzymes of glycolysis are inhibited. Also, enzymes of fatty acid oxidation are activated.