A relationship between Cellular respiration, ketone bodies and Diabetes Mellitus
Our cells take up glucose from the blood and oxidize it through cellular respiration, producing energy which is stored in an intermediate molecule called adenosine triphosphate (ATP).
When we are exercising or in a starved state, glucose in our blood stream is quickly taken into a cell and used up. Cells take the situation of low glucose in the cytosol as a sign of high energy demand. In order to meet energy demands, additional triglycerides in adipose tissue can be hydrolysed to produce free fatty acid. Fatty acids are typically used as systemic energy storage because 1g of fat actually stores more energy than 1g of glucose.
Fatty acids are carried through the bloodstream towards liver where they are converted into ketones under conditions of continuous starvation. However, liver can’t use ketones because hepatocytes lack certain enzymes. Instead, liver returns them into the bloodstream and these ketone bodies in turn are taken up by our body cells.
In cells, ketone bodies (molecules) are broken down into acetyl-coA, a key molecule for TCA cycle to run and ultimately drive the formation of ATP via oxidative phosphorylation in cellular respiration. This is one way, fat provides us with energy. Then, why didn’t evolution favor human use fats instead of glucose as primary energy source?
Ketone bodies (3 type of molecules) have a carboxyl group, -COOH group. They tend to dissociate in the blood (pH of 7.4), thereby acting as an acid. High school biology has taught us that enzymes are highly sensitive to pH and have a very narrow range of optimal pH values. Dissociate protons from ketone bodies will lower the blood pH, which is not great from your body’s proteins.
Diabetes Mellitus comes in…
The good news is that short-term increase of ketone bodies in the blood during activities like exercising doesn’t affect our body. However, chronic conditions like type 2 diabetes mellitus (DM) leads to consistently high blood ketone bodies and high blood glucose. Normally, insulin helps to stimulate the absorption of excess glucose into blood cells. However in DM patient, insulin isn’t loses efficacy and excess blood glucose cannot enter the cells. Cells take “low cytosolic glucose level” as a sign of high energy demand and start producing ketones.
What happens with Diabetes Mellitus?
High blood glucose osmotically pulls intracellular fluid into the blood in an attempt to equalize its tonicity with the cells, bringing the concentration of blood glucose levels close to normal while dehydrating the cells. Meanwhile in the kidneys, the normal glucose reabsorption capacity is reached and large amounts of glucose are excreted in the urine in a condition called osmotic diuresis.
Overall it causes diffusion of fluid from cells into the bloodstream and out of the body. The result is excessive thirst (polydipsia) and excessive urine production (polyuria). The cells are deprived of glucose and will signal their ‘hunger’ by releasing hormones to the brain (excessive hunger- polyphagia). Other symptoms include sudden weight loss as the body is breaking down the fat store to supply energy to compensate for the insufficient supply of energy by glucose oxidation. The poor glucose supply (due to insulin malfunction) causes energy supply reduction, the person may become fatigued and may resort to high carbohydrate food which further aggravate the situation. Nocturnal (night) polyuria may also affect patient’s sleep and make the situation worse.
Any doctor who hears their patient complaining of characteristic symptoms such as frequent polydipsia, polyuria and polyphagia will immediately consider a blood glucose meter. [SC7]
The circulatory system carries out many important functions. Any alteration in blood content may lead to many complications including diabetic nephropathy, diabetic retinopathy, and slow wound healing.
Diabetes Mellitus is a long term condition, it not only causes health complication, it also has a negative impact on their quality of life. However, with a healthy lifestyle and careful diet control together with medication, well controlled diabetes mellitus isn’t life threatening.
Reference: http://www.diabetesselfmanagement.com/managing-diabetes/blood-glucose-management/high-blood-glucose/
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