Acetoacetic acid (=acetoacetate) is a ketone body and a weak Beta-keto acid produced from acetyl-CoA in the mitochondrial matrix of hepatocytes.
When there is decreased availability of glucose or impaired glucose metabolism, such as in diabetes mellitus, the acetyl-CoA is diverted to produce more acetoacetate, from which acetone and beta-hydroxybutyrate are formed. Since acetoacetate and beta-hydroxybutyrate are water soluble, they can circulate from the liver to other tissues, where both compounds are reconverted to acetyl-CoA to produce energy through the citric acid cycle. When the rate of synthesis of acetoacetate and other ketone bodies exceeds the rate of utilization, their concentration in blood increases, a phenomenon known as ketonemia.
What are Ketones?
- Ketones or ketone bodies are byproducts of fat metabolism.
- There are three ketone bodies produced by the body: acetone, acetoacetate, and beta-hydroxybutyrate.
- Ketone bodies are constantly produced in insignificant amounts by the liver.
- Acetoacetate is created first.
- Beta-hydroxybutyrate is created from acetoacetate.
- Beta-hydroxybutyrate is the predominant ketone body present in severe diabetic ketoacidosis (DKA).
- Acetone is a spontaneously created side product of acetoacetate.
What is ketoacidosis?
Glucose (a type of sugar) is the body's main energy source. But when the body can't use glucose for fuel - like when a person has untreated diabetes - the body breaks down fat for energy instead. When fat is broken down, the body produces ketones, which appear in the blood and urine. High levels of ketones cause the blood to become more acidic. This is known as ketoacidosis (it's called diabetic ketoacidosis, or DKA, when uncontrolled diabetes is the cause).
Ketoacidosis is a severe life-threatening condition requiring immediate treatment. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, rapid breathing, and, in severe cases, unconsciousness.
What is ketonemia?
This describes the condition when abnormally high amounts of ketones are present in the blood.
What is ketonuria?
This describes the condition when abnormally high amounts of ketones are present in the urine.
Extreme accumulation of acetoacetic acid and other ketones can lead to metabolic acidosis defined as ketoacidosis. High levels of acetoacetate in blood may result from the following:
- Decreased availability of carbohydrates (eg, starvation, alcoholism)
- Abnormal use of carbohydrates storage (eg, uncontrolled diabetes, glycogen storage diseases)
Most common forms of ketoacidosis:
Diabetic ketoacidosis and alcoholic ketoacidosis are by far the most common forms of elevated acetoacetate level and ketosis.
Other common causes of elevated ketones are:
- prolonged fasting
- protein malnutrition
- high fat diet
- vitamin B12 deficiency
- severe GI Candida overgrowth
- and pulmonary infections
Ketonuria may be seen in:
- uncontrolled diabetes mellitus
- strenuous exercise
- certain inherited metabolic diseases with abnormalities of carbohydrate or lipid metabolism.
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