Ketogenesis

A vital topic for your NEET curriculum, ketogenesis is a metabolic process through which energy is produced for the body. It works by creating ketone bodies. Each ketone body can produce up to 22 ATP under normal circumstances. 

Ketone body synthesis fastens in the presence of increased fatty acids and lack of carbohydrate. A process which is functional almost all the time, ketone bodies can be used as an alternative source of energy. Moreover, during fasting and overnight sleep, ketone bodies increase in blood. 

However, excessive ketogenesis often results in ketoacidosis, which in turn is responsible for uncontrolled diabetes.  

Characteristics of Ketone Bodies

The formation of Ketone bodies takes place in the liver in the absence of glucose. The two primary ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB). These two components are acidic and have pKa values 3.6 and 4.7, respectively. The other less abundant ketone body is acetone. 

Ketone body synthesis helps in breaking down fatty acids. They consist of two R groups attached to a carbonyl group. Basically, ketones are water-soluble lipid molecules. Notably,it is for this characteristic that they do not need lipoproteins for transport. Most tissues and organs usually use ketone bodies as an alternative energy source. 

 Ketogenesis Pathway

Ketogenesis happens in the human body almost all the time for energy production. The normal ketone body synthesis pathway creates energy from stored carbohydrate or non-carbohydrate components. 

Ketone body synthesis takes place in different circumstances. The possibilities are the following. 

• Glycogenolysis is the primary process of synthesis when there is ample stored carbohydrate available. This process breaks down the glycogen stored in liver and muscle. 

• Gluconeogenesis is the process by which glucose is produced from a non-carbohydrate substance like lactate. This process commonly occurs during exercise. 

• A process called ketoacidosis occur when stored carbohydrate supply goes down significantly, and the concentration of fatty acid increases. In such a case, the ketogenic pathway overproduces ketone bodies. This situation may lead to type 1 diabetes. Furthermore, it can result from starvation and alcoholism as well. 

Steps of Ketogenesis

The ketone body synthesis through ketogenesis takes place in mitochondria of liver cells. The steps, which have been illustrated in the image above, are also explained below.

1. Fatty acids are transported into mitochondria via CPT-1. Then through beta-oxidation, acetyl CoA breaks it down. 

2. Enzyme thiolase helps in converting two Acetyl CoA molecules into acetoacetyl CoA. 

3. Then the enzyme HMG-CoA converts acetoacetyl CoA into HMG-CoA. 

4. Next, HMG-CoA lyase transforms HMG-CoA into acetoacetate.

5. Acetoacetate then converts into acetone via non-enzymatic decarboxylation. Under specific circumstances, it also transforms into beta-hydroxybutyrate via - hydroxybutyrate Dehydrogenase. 

Once these two ketone bodies reach extrahepatic tissues, 

• β-Hydroxybutyrate converts into acetoacetate, and it further transforms into acetyl CoA via enzyme -ketoacyl-CoA transferase.

• Acetyl CoA takes part in the citric cycle and then creates oxidative phosphorylation via 22 ATP/molecule. 

• Acetone finally leaves the body through expiration or urine as it cannot be converted back into acetyl CoA.  

Importance of Ketogenesis

• Ketogenesis provides energy to the heart, brain, and skeleton muscles, especially during fasting. The brain cannot absorb fatty acid directly; hence it gets adequate energy from this biochemical process. 

• The keto diet or low carb and fat-based diet are getting popular nowadays to lose bodyweight. However, excessive ketogenic production may lead to ketoacidosis. 

• Overt production of ketone bodies increases the glycaemic index and makes a body dehydrated. This condition arises from reduced water absorption into the liver. 

• The primary hormonal regulator of ketogenesis is insulin. Therefore, people with diabetes suffer the most from ketoacidosis. 

• Ketoacidosis can be detected initially through some symptoms like bad breath, fatigue, weight loss, frequent urination, excessive thirst, etc. 

• However, ketone bodies can be measured through a urinalysis. On the other hand, acetone in the blood can be detected with a blood serum test. 

Ketogenesis Regulation

Hormones like cortisol, thyroid hormones, glucagon, etc. aid in hastening Ketogenesis process by breaking down free fatty acids. 

Moreover, insulin regulates several enzymes in the ketogenic pathway. In the process, lower insulin level may lead to

• Rise in free fatty acid accumulation.

• Mitochondria absorbing increased free fatty acids (FFA).

• Higher production of ketone bodies. 

These two terms are often mistaken especially since they are similar. Since they are not, it is vital to note their differences in detail. This following table illustrates the same. 

Ketosis Vs Ketoacidosis

Pop Quiz

1. During prolonged fasting, the urine of a person contains a high percentage of

1. Ketone

2. Amino acids

3. Fats

4. Glucose

2. Fill in the blank: fatty acids travel from cytosol to mitochondria through ________________. 

Answers: 1-a), 2- Carnitine. 

Study Smart and Do Not Forget to Revise

A subject like biology may seem simple and easy. In reality however, it is not, especially if exams are just around the corner. Hence, try to cover the complete syllabus early so that you get ample time to revise thoroughly. Topics like Ketogenesis, gluconeogenesis, etc. require extra attention because of its intricate detailing. 

Also acquiring mastery on a concept like ketone body synthesis takes up a sumptuous amount of time. Besides, also follow a healthy diet and maintain a proper sleep cycle of 7-8 hours a day to keep your physical and mental health intact. Follow these tips and success will be yours.