Many of the biochemical reactions in a living cell can go both ways. For example, mammalian cells both catabolize and synthesize glucose. The rates at which these reactions occur must be regulated; otherwise, energy is wasted by what is called a futile cycle carrying out opposing reactions at high rates with no net substrate flow in either direction. Remember that the Second Law of Thermodynamics states that entropy increases in a favored reaction; entropy is wasted energy in that it can't be used to carry out work. Sometimes an enzyme that uses ATP as a substrate to transfer phosphate to another molecule can hydrolyze ATP to ADP and inorganic phosphate in the absence of the other substrate. This kind of reaction would obviously consume the cell's energy without doing useful work.
is the change in the kinetic properties of an enzyme caused by binding to another molecule. The binding of a small molecule to the enzyme alters its conformation so that it carries out catalysis more or less efficiently. For example, the binding of one molecule of a substrate to an enzyme can cause it to undergo a conformational change so that it binds the next molecule of substrate more efficiently. The first conformation is termed the T (tense) state;
the second is called the R (relaxed) state.
In other words, higher concentrations of substrate favor the conversion of the T state to the R state
. This special case of regulation by substrate concentration is called cooperativity.
Another case of cooperativity is the cooperative binding of oxygen to hemoglobin. Cooperativity only operates on enzymes with more than one subunit.
Similarly, enzymes can be allosterically regulated by association with other molecules. Often the first enzyme in a metabolic pathway is feedback‐inhibited by the product of that pathway. For example, anthranilate synthetase, the first enzyme in the biosynthesis of tryptophan, is inhibited by tryptophan, but not by other amino acids. Other small molecules can act as feed‐forward activators. For example, in DNA synthesis, the amounts of purine and pyrimidine nucleotides must be kept roughly equal. The enzyme aspartate transcarbamoylase is feedback‐inhibited by CTP, the product of its metabolic pathway, and feed‐forward‐activated by ATP. If there is an excess of pyrimidines, inhibition by CTP slows the reaction, while if there is an excess of purines, ATP activates the enzyme, ultimately increasing the amount of pyrimidines in the cell.
This concept is similar to the conformational changes that occur in hemoglobin in response to changes in pH, fructose bisphosphate (FBP), and other conditions. Kinetically, these effects can be described by Hill plots where log( v/V max)/(1 ‐ v/V max) is plotted versus log[S]. The magnitude of the slope gives the minimal number of independent binding sites.