In
enzymology, the committed step (also known as the ''first'' committed step) is an effectively
irreversible enzymatic reaction
Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, calle ...
that occurs at a branch point during the biosynthesis of some
molecules.
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-determining step
In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step (RDS or RD-step or r/d step) or rate-limiting step. For a given reaction mechanism, the prediction of the ...
, 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 and
activation
Activation, in chemistry and biology, is the process whereby something is prepared or excited for a subsequent reaction.
Chemistry
In chemistry, "activation" refers to the reversible transition of a molecule into a nearly identical chemical o ...
. 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
Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes () of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of gl ...
catalyzes the first committed step of
glycolysis.
* LpxC catalyzes the first committed step of
lipid A
Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows it ...
biosynthesis.
*
8-amino-7-oxononanoate synthase catalyzes the first committed step in plant
biotin synthesis.
*
MurA catalyzes the first committed step of
peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
biosynthesis.
*
Aspartate transcarbamoylase
Aspartate carbamoyltransferase (also known as aspartate transcarbamoylase or ATCase) catalyzes the first step in the pyrimidine biosynthetic pathway ().
In '' E. coli'', the enzyme is a multi- subunit protein complex composed of 12 subunits (3 ...
catalyzes the committed step in the
pyrimidine 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 to
oxaloacetate
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...
and is the first committed step of the
Citric Acid Cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...
.
*
Acetyl-CoA carboxylase catalyzes the irreversible
carboxylation
Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylatio ...
of
acetyl-CoA to
malonyl-CoA in the first committed step of
fatty acid biosynthesis
Fatty is a derogatory term for someone who is obese. It may refer also to:
People
* Mai Fatty, Gambian politician
* Roscoe Arbuckle (1887–1933), American actor and comedian
* Fatty Briody (1858–1903), American Major League Baseball player ...
.
*
Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalyzes the chemical reaction
: D-glucose 6-phosphate + NADP+ + H2O 6-phospho-D-glucono-1,5-lactone + NADPH + H+
This enzyme participates in the pentose phospha ...
catalyzes the conversion of
G6P
Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this way ...
into
6-phosphogluconolactone
6-Phosphogluconolactone is an intermediate in the pentose phosphate pathway (PPP).
In the PPP pathway, it is produced from glucose-6-phosphate by glucose-6-phosphate dehydrogenase. It is then converted to 6-Phosphogluconic acid by 6-phosphoglu ...
to produce
NADPH in the first and committed step of the
pentose phosphate pathway
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
.
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
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
.
See also
*
Enzyme catalysis
Enzyme catalysis is the increase in the reaction rate, rate of a process by a Biomolecule, biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs ...
*
Negative feedback
References
{{Reflist
External links
''Glycolysis Regulation''at Cliffsnotes.com
Enzymes
Catalysis
Biomolecules
Biosynthesis