Substrate analogs (substrate state analogues), are
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s with a
chemical structure
A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...
that resemble the
substrate molecule in an
enzyme-catalyzed chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
. Substrate analogs can act as
competitive inhibitors of an enzymatic reaction. An example is
phosphoramidate to the ''
Tetrahymena'' group I ribozyme. Other examples of substrate analogs include 5’-adenylyl-imidodiphosphate, a substrate analog of
ATP, and 3-acetylpyridine adenine dinucleotide, a substrate analog of
NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...
.
As a competitive inhibitor, substrate analogs occupy the same binding site as its analog, and decrease the intended substrate’s efficiency. The maximum rate (V
max) remains the same while the intended substrate’s affinity (measured by the
Michaelis constant K
M) is decreased. This means that less of the intended substrate will bind to the enzyme, resulting in less product being formed. In addition, the substrate analog may also be missing chemical components that allow the enzyme to go through with its reaction. This also causes the amount of product created to decrease.
Substrate analogs usually bind to the binding site reversibly. This means that the binding of the substrate analog to the enzyme’s binding site is non-permanent. The effect of the substrate analog can be nullified by increasing the concentration of the originally intended substrate. There are also substrate analogs that bind to the binding site of an enzyme irreversibly. If this is the case, the substrate analog is called an inhibitory substrate analog, a suicide substrate, or a Trojan horse substrate. An example of a substrate analog that is also a suicide substrate/Trojan horse substrate is
penicillin
Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
, which is an inhibitory substrate analog of
peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...
.
Some substrate analogs can still allow the enzyme to synthesize a product despite the enzyme’s inability to metabolize the substrate analog. These substrate analogs are known as gratuitous inducers. An example of a substrate analog that is also a gratuitous inducer is
IPTG (isopropyl β-D-1-thiogalactopyranoside), a substrate analog and gratuitous inducer of
β-galactosidase
β-Galactosidase (EC 3.2.1.23, beta-gal or β-gal; systematic name β-D-galactoside galactohydrolase) is a glycoside hydrolase enzyme that catalyzes hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides. (This enzym ...
activity.
[Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ]
See also
*
Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
*
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted ...
*
Suicide inhibitor
*
Structural analog
A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component.
It can ...
, compounds with similar chemical structure
References
{{Reflist
Enzyme kinetics
Chemical nomenclature