enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, the committed step (also known as the ''first'' committed step) is an effectively

irreversible Irreversible may refer to: * Irreversible process, in thermodynamics, a process that is not reversible *'' Irréversible'', a 2002 film * ''Irréversible'' (soundtrack), soundtrack to the film ''Irréversible'' * An album recorded by hip-hop artis ...

enzymatic reaction that occurs at a branch point during the biosynthesis of some

molecules A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

. As the name implies, after this step, the molecules are "committed" to the

pathway Pathway or pathways may refer to: Entertainment * ''The Pathway'' (novel), a 1914 work by Gertrude Page *''The Pathway'', a 2001 album by Officium Triste * ''Pathway'' (album), by the Flaming Stars * ''Pathways'' (album) (2010), by the Dave Hol ...

and will ultimately end up in the pathway's final product. The first committed step should not be confused with the rate-determining step, which is the slowest step in a reaction or pathway. However, it is sometimes the case that the first committed step is in fact the rate-determining step as well.

Regulation

Metabolic pathways require tight regulation so that the proper compounds get produced in the proper amounts. Often, the first committed step is regulated by processes such as

feedback inhibition An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

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

* Phosphofructokinase 1 catalyzes the first committed step of

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

. * LpxC catalyzes the first committed step of lipid A biosynthesis. * 8-amino-7-oxononanoate synthase catalyzes the first committed step in plant

biotin Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', bor ...

synthesis. * MurA catalyzes the first committed step of peptidoglycan biosynthesis. * Aspartate transcarbamoylase catalyzes the committed step in the

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...

biosynthetic pathway in ''E. coli''. *3-deoxy-D-arabinose-heptulsonate 7-phosphate synthase catalyses the first committed step of the shikimate pathway responsible for the synthesis of the aromatic amino acids Tyrosine, Tryptophan and Phenylalanine in plants, bacteria, fungi and some lower eukaryotes. *Citrate synthase catalyzes the addition of

acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

to oxaloacetate and is the first committed step of the Citric Acid Cycle. *

Acetyl-CoA carboxylase Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme () that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is ...

catalyzes the irreversible carboxylation of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...

in the first committed step of fatty acid biosynthesis. * Glucose-6-phosphate dehydrogenase catalyzes the conversion of G6P into 6-phosphogluconolactone to produce

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...

in the first and committed step of the pentose phosphate pathway.

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.

References

{{Reflist

External links

''Glycolysis Regulation''
at Cliffsnotes.com Enzymes Catalysis Biomolecules Biosynthesis

Regulation

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

Other uses

See also

References

External links