AssessmentsKetone body metabolism
Ketone body metabolism
USMLE® Step 1 style questions USMLE
A patient with uncontrolled diabetes mellitus is admitted to the intensive care unit for the management of diabetic ketoacidosis. One of the medical students notices that the patient's breath smells sweet, similar to the odor of fruits. Which of the following ketone bodies is responsible for this odor?
Content Reviewers:Rishi Desai, MD, MPH
In life, it’s helpful to have a plan B in case plan A doesn’t work out.
But if these main fuels aren’t readily available, then plan B is to use an alternative fuel source - ketone bodies.
Ketone bodies are a group of carbon-containing molecules produced by liver mitochondria using a 2-carbon molecule called acetyl-CoA.
Ketone bodies can be released into the circulation and get picked up by the majority of cells.
Inside the cells, they’re reconverted back into acetyl-CoA, at which point they can then enter the mitochondria and produce ATP.
The 3 primary ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone.
Alright, so let’s say you decide to go on a 5-day fast.
About 12 hours into your fast, your blood glucose levels start to dip.
Then, around 1 to 3 days into your fast, your body begins to run out of the necessary substrates to make new glucose.
So, it switches to breaking down fatty acids for energy.
Fatty acids are mobilized from fat stores and are broken down to acetyl CoA through beta oxidation in the mitochondria of most cells - except for brain cells.
This makes sense from the liver’s standpoint as well because normally, acetyl-CoA combines with oxaloacetate in the citric acid cycle to make citrate.
But since oxaloacetate is also a substrate for gluconeogenesis, so it’s levels are pretty depleted at this point in starvation.
So oxaloacetate basically leaves all that acetyl-CoA hanging out by itself. Not cool oxaloacetate, not cool.
Ketone body synthesis begins with 2 acetyl-CoA molecules getting joined together by the enzyme acetyl-CoA acyl-transferase.
The result is a 4-carbon molecule called acetoacetyl-CoA and then a free CoA molecule.
Next, the enzyme HMG-CoA synthase combines acetoacetyl-CoA and acetyl-CoA to form a 6-carbon molecule called 3-hydroxy-3-methylglutaryl CoA, or HMG-CoA - so 3 acetyls and then a free CoA molecule.
Ketone bodies like beta-hydroxybutyrate and acetoacetate are an alternative source of energy in states of prolonged starvation. Ketone body synthesis occurs in the liver in physiologic states like prolonged fasting or exercise, as well as in pathological states like type 1 diabetes mellitus or alcoholism. Once synthesized, ketone bodies can leave the liver, and enter into peripheral cells such as the brain, skeletal muscle and kidney to serve as energy sources.