Inchemistry,de novo synthesis (from Latin 'from the new') is thesynthesis of complex molecules from simple molecules such assugars oramino acids, as opposed to recycling after partialdegradation. For example,nucleotides are not needed in the diet as they can be constructed from smallprecursor molecules such asformate andaspartate.Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated fromhomocysteine, it cannot be synthesizedde novo.
De novo pathways ofnucleotides do not use free bases:adenine (abbreviated as A),guanine (G),cytosine (C),thymine (T), oruracil (U). Thepurine ring is built up one atom or a few atoms at a time and attached toribose throughout the process.[1] Pyrimidine ring is synthesized asorotate and attached toribose phosphate and later converted to commonpyrimidine nucleotides.
Cholesterol is an essential structural component ofanimalcell membranes. Cholesterol also serves as aprecursor for thebiosynthesis ofsteroid hormones,bile acid[2] andvitamin D. In mammals cholesterol is either absorbed from dietary sources or is synthesizedde novo. Up to 70-80% ofde novo cholesterol synthesis occurs in theliver, and about 10% ofde novo cholesterol synthesis occurs in thesmall intestine.[3] Cancer cells require cholesterol for cell membranes, so cancer cells contain many enzymes forde novo cholesterol synthesis fromacetyl-CoA.[3]
De novolipogenesis (DNL) is the process by which excess carbohydrates[4] from the circulation are converted intofatty acids, which can be further converted intotriglycerides or other lipids.[5]Acetate and some amino acids (notablyleucine andisoleucine) can also be carbon sources for DNL.[6]
Normally,de novo lipogenesis occurs primarily inadipose tissue. But in conditions ofobesity,insulin resistance, ortype 2 diabetesde novo lipogenesis is reduced in adipose tissue (wherecarbohydrate-responsive element-binding protein (ChREBP) is the majortranscription factor) and is increased in the liver (wheresterol 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 tissuede novo lipogenesis, and the increase in liverde novo lipogenesis due to obesity and insulin resistance leads tofatty 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 increasesde 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 inabdominal fat.[8]
DNL is elevated innon-alcoholic fatty liver disease (NAFLD), and is a hallmark of the disease.[9] Compared with healthy controls, patients with NAFLD have an average 3.5-fold increase in DNL.[9]
De novo fatty-acid synthesis is regulated by two important enzymes, namelyacetyl-CoA carboxylase andfatty acid synthase.[6] 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.[10] Thus, it is considered to be a minor contributor to the serum lipid homeostasis.[4] In mice,FAde novo synthesis increases inWAT with the exposure to cold temperatures which might be important for maintenance of circulatingTAG levels in the blood stream, and to supplyFA forthermogenesis during prolonged cold exposures.[11]
De novoDNA synthesis refers to the synthetic creation of DNA rather than assembly or modification of natural precursor template DNA sequences.[12] Initialoligonucleotide synthesis is followed byartificial gene synthesis, and finally by a process ofcloning, error correction, and verification, which often involves cloning the genes intoplasmids inEscherichia coli oryeast.[12]
Primase is anRNA 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 primerde novo.