Cholesterol is essential for life, and a key in the development of heart disease. Cholesterol homeostasis is achieved through regulation of cholesterol uptake, cholesterol biosynthesis, cholesterol conversion to bile acids, and the excretion of bile acids.

The synthesis and utilization of cholesterol must be tightly regulated in order to prevent over-accumulation and abnormal deposition within the body. Of particular importance clinically is the abnormal deposition of cholesterol and cholesterol-rich lipoproteins in the coronary arteries. Such deposition, eventually leading to atherosclerosis, is the leading contributory factor in diseases of the coronary arteries.

Cholesterol is either obtained from the diet or synthesized in a variety of tissues, including the liver, adrenal cortex, skin, intestine, testes, and aorta. High dietary cholesterol suppresses synthesis in the liver but not in other tissues.

Carbohydrate is converted to triglyceride-utilizing glycerol phosphate and acetyl CoA obtained from glycolysis. Ketogenic amino acids, which are metabolized to acetyl CoA, may be used for synthesis of triglycerides. The fatty acids cannot fully prevent protein breakdown, because only the glycerol portion of the triglycerides can contribute to gluconeogenesis. Glycerol is only 5% of the triglyceride carbon.

Most of the major tissues (e.g., muscle, liver, kidney) are able to convert glucose, fatty acids, and amino acids to acetyl-CoA. However, brain and nervous tissue — in the fed state and in the early stages of starvation — depend almost exclusively on glucose. Not all tissues obtain the major part of their ATP requirements from the Krebs cycle. Red blood cells, tissues of the eye, and the kidney medulla gain most of their energy from the anaerobic conversion of glucose to lactate.