De novo synthesis

Synthesis of complex molecules from simple precursors

In chemistry, de novo synthesis is the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate. Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated from homocysteine, it cannot be synthesized de novo.

De novo pathways of nucleotides do not use free bases: adenine (abbreviated as A), guanine (G), cytosine (C), thymine (T), or uracil (U). The purine ring is built up one atom or a few atoms at a time and attached to ribose throughout the process. Pyrimidine ring is synthesized as orotate and attached to ribose phosphate and later converted to common pyrimidine nucleotides.

Cholesterol is an essential structural component of animal cell membranes. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid 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. Cancer cells require cholesterol for cell membranes, so cancer cells contain many enzymes for de novo cholesterol synthesis from acetyl CoA. from the circulation are converted into fatty acids, which can be further converted into triglycerides or other lipids. Acetate and some amino acids (notably leucine and isoleucine) can also be carbon sources for DNL. 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. 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. Compared with healthy controls, patients with NAFLD have an average 3.5  fold increase in DNL. The enzyme acetyl CoA carboxylase is responsible for introducing a carboxyl group to acetyl CoA, rendering malonyl CoA. Then, the enzyme fatty acid synthase is responsible for turning malonlyl CoA into fatty acid chain. De novo fatty acid synthesis is mainly not active in human cells, since diet is the major source for it. Thus, it is considered to be a minor contributor to the serum lipid homeostasis.

De novo DNA synthesis refers to the synthetic creation of DNA rather than assembly or modification of natural precursor template DNA sequences. 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. 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.