De novo synthesis

In

De novo pathways of

Cholesterol

Cholesterol is an essential structural component of animal cell membranes. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid^[2] and vitamin D. In mammals cholesterol is either absorbed from dietary sources or is synthesized de novo. Up to 70-80% of de novo cholesterol synthesis occurs in the liver, and about 10% of de novo cholesterol synthesis occurs in the small intestine.^[3] Cancer cells require cholesterol for cell membranes, so cancer cells contain many enzymes for de novo cholesterol synthesis from acetyl-CoA.^[3]

Fatty-acid (de novo lipogenesis)

De novo lipogenesis (DNL) is the process by which excess carbohydrates^[4] from the circulation are converted into fatty acids, which can be further converted into triglycerides or other lipids.^[5] Acetate and some amino acids (notably leucine and isoleucine) can also be carbon sources for DNL.^[6]

Normally, de novo lipogenesis occurs primarily in adipose tissue. But in conditions of obesity, insulin resistance, or type 2 diabetes de novo lipogenesis is reduced in adipose tissue (where carbohydrate-responsive element-binding protein (ChREBP) is the major transcription factor) and is increased in the liver (where sterol regulatory element-binding protein 1 (SREBP-1c) is the major transcription factor).^[5] ChREBP is normally activated in the liver by glucose (independent of insulin).^[7] Obesity and high-fat diets cause levels of carbohydrate-responsive element-binding protein in adipose tissue to be reduced.^[5] By contrast, high blood levels of insulin, due to a high carbohydrate meal or insulin resistance, strongly induces SREBP-1c expression in the liver.^[7] The reduction of adipose tissue de novo lipogenesis, and the increase in liver de novo lipogenesis due to obesity and insulin resistance leads to fatty liver disease.

Fructose consumption (in contrast to glucose) activates both SREBP-1c and ChREBP in an insulin independent manner.^[8] Although glucose can be converted into glycogen in the liver, fructose invariably increases de novo lipogenesis in the liver, elevating plasma triglycerides, more than glucose.^[8] Moreover, when equal amounts of glucose or fructose sweetened beverages are consumed, the fructose beverage not only causes a greater increase in plasma triglycerides, but causes a greater increase in abdominal fat.^[8]

DNL is elevated in

De novo DNA synthesis refers to the synthetic creation of DNA rather than assembly or modification of natural precursor template DNA sequences.^[12] Initial oligonucleotide synthesis is followed by artificial gene synthesis, and finally by a process cloning, error correction, and verification, which often involves cloning the genes into plasmids into Escherichia coli or yeast.^[12]

Primase is an RNA polymerase, and it can add a primer to an existing strand awaiting replication. DNA polymerase cannot add primers, and therefore, needs primase to add the primer de novo.

References