Niara Baksh and Selina Beharry - Ketoacidosis Project
Niara Baksh and Selina Beharry - Ketoacidosis Project
Niara Baksh and Selina Beharry - Ketoacidosis Project
SEMESTER: Semester II
This project will highlight the structural formula of the three ketone bodies, define ketoacidosis
and provide information on how diabetics could suffer from ketoacidosis (Using glycolysis and
the TCA cycle to explain).
Ketone bodies are known as molecules that are soluble in water due to its ability to form
hydrogen bonds with water. They contain the ketone group (R2C=O). Ketone bodies are made in
the liver and are mainly used as a backup source of energy when glucose is not available. As the
ketone bodies leave the liver and enter the tissue, they are converted into acetyl CoA which is
used to produce ATP which is used in the citric/kreb cycle as a source of energy. Factors that
may affect the production of ketone bodies include starvation, intense exercising, alcoholism or
type 1 diabetes mellitus. Acetoacetate is the first ketone body made by the excess breakdown of
fatty acids in the liver cells. Acetoacetate is synthesized by two acetyl CoA molecules (main
precursor of ketone bodies) and can either be broken down to produce acetone or converted into
BHB to aid in transportation of the blood. In other cases, it can be taken up into cells (for
energy). Acetone (least abundant) is another example of a ketone and is produced as a side
product of acetoacetate (by enzymatic decarboxylation) and is excreted from the body through
exhaling and urine. It is also able to break down quickly but is not used for energy production.
Beta-hydroxybutyric acid (BHB) is the last ketone body formed from acetoacetate but is not
considered a true ketone because of its structure. Even though it is not a true ketone, it is still
considered one that is used for energy during times where the glucose level is too low. It is the
most useful in energy production when glycogen and insulin levels are very low and when
glucagon are high. The energy form this is used in the muscle, brain, heart and other tissues.
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The structural formula of the ketone bodies:
Acetoacetate:
Acetone:
2
What is Diabetic Ketoacidosis?
Diabetic Ketoacidosis (DKA) is a life-threatening complication that can occur in diabetics when
blood sugar levels rise exceedingly high, causing an increase of ketones in the blood. DKA is
most frequent in type 1 diabetes patients; however it can also occur in type 2 diabetic patients.
DKA is commonly caused by inadequate insulin administration in type 1 and type 2 diabetics,
such as missed insulin injections or having a malfunctioning device, infections or illness, and
cardiovascular disorders such as heart attack and stroke. In order to understand how this
condition occurs, it is important to examine the role of glycolysis and the TCA cycle in glucose
metabolism.
Glucose is the fundamental energy source of the body, derived from carbohydrate breakdown
and transported to numerous organs via the bloodstream. Glycolysis is the process by which
glucose is converted into pyruvate, yielding a net of two molecules of ATP. Insulin is a hormone
produced by beta cells in the pancreas that is responsible for pushing glucose into cells. In
diabetics, insulin resistance or a lack of insulin can prevent glucose from entering cells, resulting
in a buildup of glucose in the bloodstream. As a result, the body attempts to compensate by
increasing glucose breakdown through glycolysis in order to synthesize more ATP. This excess
glucose can be absorbed by the liver and converted into pyruvate via glycolysis, resulting in the
production of ATP.
However, when the supply of glucose exceeds the demand for energy, surplus pyruvate can be
converted into acetyl-CoA and enter the TCA cycle. The TCA cycle is a sequence of chemical
reactions involving the extraction of energy from acetyl-CoA while producing ATP and carbon
dioxide as byproducts. To actually utilize acetyl-coA from the beta oxidation of fatty acids to
help us generate citrate (the intermediate of the TCA cycle), which is necessary to help us
produce ATP molecules, substantial quantities of oxaloacetate are required. As a result of the
liver's low levels of oxaloacetate caused by inadequate glucose absorption in diabetics, the TCA
cycle may become overloaded by high amounts of acetyl-CoA resulting in ketone compounds
including beta-hydroxybutyrate and acetoacetate being produced.
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Normally, ketones are produced in small amounts during periods of fasting or prolonged
exercise, and are used as an alternative fuel source by the brain and other tissues. However, in
individuals with diabetes, high levels of ketones can lead to a condition known as ketoacidosis.
This occurs when the excess acetoacetate and beta-hydroxybutyrate enter the bloodstream and
they dissociate releasing H+ ions lowering the pH of the blood, making it more acidic and
potentially causing damage to organs such as the kidneys, liver, and brain.
In order to prevent ketoacidosis, individuals with diabetes must carefully monitor their blood
sugar levels and take steps to avoid extreme fluctuations. This may involve regular insulin
injections, dietary adjustments, and exercise.
Additionally, it is important for individuals with diabetes to be aware of the signs and
symptoms of ketoacidosis, which can include the following:
- Nausea
- Vomiting
- Abdominal pain, shortness of breath,
- Excessive urine output (polyuria),
- Excessive thirst (polydipsia)
- Confusion
- Fruity-smelling breath (produced by excess acetone that is not metabolized by body cells
and is exhaled through breath)
DKA= 3mmol/L
4
In a urine ketone test, those with DKA will show a test result of 2+ or more.
In conclusion, diabetics may develop ketoacidosis as a result of decreased insulin production and
excessive glucose levels. The glycolysis and TCA cycles have an impact in the progression of
ketoacidosis. Excess ketone bodies produced by fatty acid breakdown can result in a reduction in
blood pH and diabetic ketoacidosis, both of which can be fatal. Diabetics must constantly
monitor their blood glucose levels and seek medical assistance if they exhibit symptoms of
ketoacidosis.
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References
https://youtu.be/LwLWo6kUst4
Diabetic Ketoacidosis. (2021, March 25). Centers for Disease Control and Prevention.
https://www.cdc.gov/diabetes/basics/diabetic-ketoacidosis.html#:~:text=DKA%20is
%20most%20common%20among,that%20produces%20acids%20called%20ketones.
https://www.ncbi.nlm.nih.gov/books/NBK534848/