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De novo synthesis

February 15, 2024

In chemistry, de novo synthesis (from Latin 'from the new') 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.

Nucleotide edit

See also: Nucleotide § Synthesis

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.[1] Pyrimidine ring is synthesized as orotate and attached to ribose phosphate and later converted to common pyrimidine nucleotides.

Cholesterol edit

See also: Cholesterol § Biosynthesis

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) edit

See also: Fatty acid synthesis

De novo lipogenesis (DNL) is the process by which carbohydrates (primarily, especially after a high-carbohydrate meal) from the circulation are converted into fatty acids, which can be further converted into triglycerides or other lipids.[4] Acetate and some amino acids (notably leucine and isoleucine) can also be carbon sources for DNL.[5]

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).[4] ChREBP is normally activated in the liver by glucose (independent of insulin).[6] Obesity and high-fat diets cause levels of carbohydrate-responsive element-binding protein in adipose tissue to be reduced.[4] By contrast, high blood levels of insulin, due to a high carbohydrate meal or insulin resistance, strongly induces SREBP-1c expression in the liver.[6] 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.[7] 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.[7] 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.[7]

DNL is elevated in non-alcoholic fatty liver disease (NAFLD), and is a hallmark of the disease.[8] Compared with healthy controls, patients with NAFLD have an average 3.5 -fold increase in DNL.[8]

De novo fatty-acid synthesis is regulated by two important enzymes, namely acetyl-CoA carboxylase and fatty acid synthase.[5] 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.[9] In mice, FA de novo synthesis increases in WAT with the exposure to cold temperatures which might be important for maintenance of circulating TAG levels in the blood stream, and to supply FA for thermogenesis during prolonged cold exposures.[10]

DNA edit

See also: Artificial gene synthesis

De novo DNA synthesis refers to the synthetic creation of DNA rather than assembly or modification of natural precursor template DNA sequences.[11] 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.[11]

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 edit

  1. ^ Ali, Eunus S.; Sahu, Umakant; Villa, Elodie; O’Hara, Brendan P.; Gao, Peng; Beaudet, Cynthia; Wood, Antony W.; Asara, John M.; Ben-Sahra, Issam (1 June 2020). "ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis". Molecular Cell. 78 (6): 1178–1191.e6. doi:10.1016/j.molcel.2020.05.001. ISSN 1097-2765. PMC 7306006. PMID 32485148.
  2. ^ Hanukoglu I (Dec 1992). "Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis". J Steroid Biochem Mol Biol. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824. S2CID 112729.
  3. ^ a b Yang J, Wang L, Jia R (2020). "Role of de novo cholesterol synthesis enzymes in cancer". Journal of Cancer. 11 (7): 1761–1767. doi:10.7150/jca.38598. PMC 7052851. PMID 32194787.
  4. ^ a b c Song Z, Xiaoli AM, Yang F (2018). "Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues". Nutrients. 10 (10): E1383. doi:10.3390/nu10101383. PMC 6213738. PMID 30274245.
  5. ^ a b Wallace M, Metallo CM (2020). "Tracing insights into de novo lipogenesis in liver and adipose tissues". Seminars in Cell and Developmental Biology. 41 (1): 65–71. doi:10.1016/j.semcdb.2020.02.012. PMID 32201132. S2CID 214617840.
  6. ^ a b Xu X, So JS, Park JG, Lee AH (2013). "Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP". Seminars in Liver Disease. 33 (4): 301–311. doi:10.1055/s-0033-1358523. PMC 4035704. PMID 24222088.
  7. ^ a b c Herman MA, Samuel VT (2016). "The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis". Trends in Endocrinology & Metabolism. 27 (10): 719–730. doi:10.1016/j.tem.2016.06.005. PMC 5035631. PMID 27387598.
  8. ^ a b Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW (2020). "Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management". Endocrine Reviews. 41 (1): 66–117. doi:10.1210/endrev/bnz009. PMID 31629366.
  9. ^ Mashima T, Seimiya H, Tsuruo T (May 2009). "De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy". British Journal of Cancer. 100 (9): 1369–72. doi:10.1038/sj.bjc.6605007. PMC 2694429. PMID 19352381.
  10. ^ Flachs, P; Adamcova, K; Zouhar, P; Marques, C; Janovska, P; Viegas, I; Jones, J G; Bardova, K; Svobodova, M; Hansikova, J; Kuda, O (March 2017). "Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype". International Journal of Obesity. 41 (3): 372–380. doi:10.1038/ijo.2016.228. ISSN 0307-0565. PMID 28008171. S2CID 4111899.
  11. ^ a b Kosuri S, Church GM (2014). "Large-scale de novo DNA synthesis: technologies and applications". Nature Methods. 11 (5): 499–507. doi:10.1038/nmeth.2918. PMC 7098426. PMID 24781323.

Further reading edit

  • Harper's Illustrated Biochemistry, 26th Ed - Robert K. Murray, Darryl K. Granner, Peter A. Mayes, Victor W. Rodwell
  • Lehninger Principles of Biochemistry, Fourth Edition - David L. Nelson, Michael M. Cox
  • Biochemistry 5th ed - Jeremy M. Berg, John L. Tymoczko, Lubert Stryer
  • Biochemistry- Garrett.and.Grisham.2nd.ed
  • Biochemistry, 2/e by Reiginald and Charles Grisham
  • Biochemistry for dummies by John T Moore, EdD and Richard Langley, PhD
  • Stryer L (2007). Biochemistry. 6th Edition. WH Freeman and Company. New York. USA

External links edit

  • Purine and pyrimidine metabolism
  • De novo synthesis of purine nucleotides

February 15, 2024
novo, synthesis, chemistry, novo, synthesis, from, latin, from, synthesis, complex, molecules, from, simple, molecules, such, sugars, amino, acids, opposed, recycling, after, partial, degradation, example, nucleotides, needed, diet, they, constructed, from, sm. In chemistry de novo synthesis from Latin from the new 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 Contents 1 Nucleotide 2 Cholesterol 3 Fatty acid de novo lipogenesis 4 DNA 5 References 6 Further reading 7 External linksNucleotide editSee also Nucleotide Synthesis 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 1 Pyrimidine ring is synthesized as orotate and attached to ribose phosphate and later converted to common pyrimidine nucleotides Cholesterol editSee also Cholesterol Biosynthesis 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 editSee also Fatty acid synthesis De novo lipogenesis DNL is the process by which carbohydrates primarily especially after a high carbohydrate meal from the circulation are converted into fatty acids which can be further converted into triglycerides or other lipids 4 Acetate and some amino acids notably leucine and isoleucine can also be carbon sources for DNL 5 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 4 ChREBP is normally activated in the liver by glucose independent of insulin 6 Obesity and high fat diets cause levels of carbohydrate responsive element binding protein in adipose tissue to be reduced 4 By contrast high blood levels of insulin due to a high carbohydrate meal or insulin resistance strongly induces SREBP 1c expression in the liver 6 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 7 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 7 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 7 DNL is elevated in non alcoholic fatty liver disease NAFLD and is a hallmark of the disease 8 Compared with healthy controls patients with NAFLD have an average 3 5 fold increase in DNL 8 De novo fatty acid synthesis is regulated by two important enzymes namely acetyl CoA carboxylase and fatty acid synthase 5 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 9 In mice FA de novo synthesis increases in WAT with the exposure to cold temperatures which might be important for maintenance of circulating TAG levels in the blood stream and to supply FA for thermogenesis during prolonged cold exposures 10 DNA editSee also Artificial gene synthesis De novo DNA synthesis refers to the synthetic creation of DNA rather than assembly or modification of natural precursor template DNA sequences 11 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 11 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 edit Ali Eunus S Sahu Umakant Villa Elodie O Hara Brendan P Gao Peng Beaudet Cynthia Wood Antony W Asara John M Ben Sahra Issam 1 June 2020 ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis Molecular Cell 78 6 1178 1191 e6 doi 10 1016 j molcel 2020 05 001 ISSN 1097 2765 PMC 7306006 PMID 32485148 Hanukoglu I Dec 1992 Steroidogenic enzymes structure function and role in regulation of steroid hormone biosynthesis J Steroid Biochem Mol Biol 43 8 779 804 doi 10 1016 0960 0760 92 90307 5 PMID 22217824 S2CID 112729 a b Yang J Wang L Jia R 2020 Role of de novo cholesterol synthesis enzymes in cancer Journal of Cancer 11 7 1761 1767 doi 10 7150 jca 38598 PMC 7052851 PMID 32194787 a b c Song Z Xiaoli AM Yang F 2018 Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues Nutrients 10 10 E1383 doi 10 3390 nu10101383 PMC 6213738 PMID 30274245 a b Wallace M Metallo CM 2020 Tracing insights into de novo lipogenesis in liver and adipose tissues Seminars in Cell and Developmental Biology 41 1 65 71 doi 10 1016 j semcdb 2020 02 012 PMID 32201132 S2CID 214617840 a b Xu X So JS Park JG Lee AH 2013 Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP Seminars in Liver Disease 33 4 301 311 doi 10 1055 s 0033 1358523 PMC 4035704 PMID 24222088 a b c Herman MA Samuel VT 2016 The Sweet Path to Metabolic Demise Fructose and Lipid Synthesis Trends in Endocrinology amp Metabolism 27 10 719 730 doi 10 1016 j tem 2016 06 005 PMC 5035631 PMID 27387598 a b Marjot T Moolla A Cobbold JF Hodson L Tomlinson JW 2020 Nonalcoholic Fatty Liver Disease in Adults Current Concepts in Etiology Outcomes and Management Endocrine Reviews 41 1 66 117 doi 10 1210 endrev bnz009 PMID 31629366 Mashima T Seimiya H Tsuruo T May 2009 De novo fatty acid synthesis and related pathways as molecular targets for cancer therapy British Journal of Cancer 100 9 1369 72 doi 10 1038 sj bjc 6605007 PMC 2694429 PMID 19352381 Flachs P Adamcova K Zouhar P Marques C Janovska P Viegas I Jones J G Bardova K Svobodova M Hansikova J Kuda O March 2017 Induction of lipogenesis in white fat during cold exposure in mice link to lean phenotype International Journal of Obesity 41 3 372 380 doi 10 1038 ijo 2016 228 ISSN 0307 0565 PMID 28008171 S2CID 4111899 a b Kosuri S Church GM 2014 Large scale de novo DNA synthesis technologies and applications Nature Methods 11 5 499 507 doi 10 1038 nmeth 2918 PMC 7098426 PMID 24781323 Further reading editHarper s Illustrated Biochemistry 26th Ed Robert K Murray Darryl K Granner Peter A Mayes Victor W Rodwell Lehninger Principles of Biochemistry Fourth Edition David L Nelson Michael M Cox Biochemistry 5th ed Jeremy M Berg John L Tymoczko Lubert Stryer Biochemistry Garrett and Grisham 2nd ed Biochemistry 2 e by Reiginald and Charles Grisham Biochemistry for dummies by John T Moore EdD and Richard Langley PhD Stryer L 2007 Biochemistry 6th Edition WH Freeman and Company New York USAExternal links editPurine and pyrimidine metabolism De novo synthesis of purine nucleotides Retrieved from https en wikipedia org w index php title De novo synthesis amp oldid 1190855987, wikipedia, wiki, book, books, library,

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