Committed step

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Schematic representation of a metabolic branch point. The numbers represent chemical compounds, whereas the letters represent enzymes that catalyze the conversion indicated by the nearby arrow. In this scheme, enzyme c catalyzes the committed step in the biosynthesis of compound 6. Committed step.png
Schematic representation of a metabolic branch point. The numbers represent chemical compounds, whereas the letters represent enzymes that catalyze the conversion indicated by the nearby arrow. In this scheme, enzyme c catalyzes the committed step in the biosynthesis of compound 6.

In enzymology, the committed step (also known as the firstcommitted step) is an effectively irreversible enzymatic reaction that occurs at a branch point during the biosynthesis of some molecules. [1] [2] As the name implies, after this step, the molecules are "committed" to the pathway and will ultimately end up in the pathway's final product. The first committed step should not be confused with the rate-limiting step, which is the step with the highest flux control coefficient. It is rare that the first committed step is in fact the rate-determining step. [3] [4]

Contents

Regulation

Metabolic pathways require tight regulation[ citation needed ] so that the proper compounds get produced in the proper amounts. Often, the first committed step is regulated by processes such as feedback inhibition and activation. Such regulation ensures that pathway intermediates do not accumulate, a situation that can be wasteful or even harmful to the cell.

Examples of enzymes that catalyze the first committed steps of metabolic pathways

Other uses

The term has also been applied to other processes that involve a series of steps. For example, the binding of egg and sperm can be thought of as the first committed step in metazoan fertilization. [10]

See also

Related Research Articles

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<span class="mw-page-title-main">Glucosamine-phosphate N-acetyltransferase</span>

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<span class="mw-page-title-main">UDP-N-acetylglucosamine 1-carboxyvinyltransferase</span> Class of enzymes

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References

  1. Bhagavan, N. V. (2002). Medical biochemistry . San Diego: Harcourt/Academic Press. ISBN   0-12-095440-0.
  2. 1 2 Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002). Biochemistry (5th ed.). W. H. Freeman and Company. p.  447. ISBN   0-7167-3051-0.
  3. Sauro, Herbert M. (February 2017). "Control and regulation of pathways via negative feedback". Journal of the Royal Society Interface. 14 (127): 20160848. doi: 10.1098/rsif.2016.0848 . PMC   5332569 . PMID   28202588.
  4. Hofmeyr, Jan-Hendrik S.; Cornish-Bowden, Athel (August 1991). "Quantitative assessment of regulation in metabolic systems". European Journal of Biochemistry. 200 (1): 223–236. doi:10.1111/j.1432-1033.1991.tb21071.x. PMID   1879427.
  5. "Phosphofructokinase Regulation". Wiley Essential Biochemistry. Retrieved 17 February 2010.
  6. Raetz C, Whitfield C (2002). "Lipopolysaccharide endotoxins". Annu Rev Biochem. 71: 635–700. doi:10.1146/annurev.biochem.71.110601.135414. PMC   2569852 . PMID   12045108.
  7. Pinon V, Ravanel S, Douce R, Alban C (2005). "Biotin synthesis in plants. The first committed step of the pathway is catalyzed by a cytosolic 7-keto-8-aminopelargonic acid synthase". Plant Physiology. 139 (4): 1666–76. doi:10.1104/pp.105.070144. PMC   1310550 . PMID   16299174.
  8. Brown ED, Vivas EI, Walsh CT, Kolter R (July 1995). "MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli". J. Bacteriol. 177 (14): 4194–7. doi:10.1128/jb.177.14.4194-4197.1995. PMC   177162 . PMID   7608103.
  9. Biochemistry & molecular biology of plants. Bob B. Buchanan, Wilhelm Gruissem, Russell L. Jones. Rockville, Md.: American Society of Plant Physiologists. 2000. ISBN   0-943088-37-2. OCLC   44162497.{{cite book}}: CS1 maint: others (link)
  10. Dell A, Chalabi S, Easton RL, et al. (December 2003). "Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15631–6. Bibcode:2003PNAS..10015631D. doi: 10.1073/pnas.2635507100 . PMC   307619 . PMID   14673092.