In metabolism, coenzymes are involved in both group-transfer reactions, for example coenzyme A and adenosine triphosphate (ATP), and redox reactions, such as coenzyme Q10 and nicotinamide adenine dinucleotide (NAD+). Coenzymes are consumed and recycled continuously in metabolism, with one set of enzymes adding a chemical group to the coenzyme and another set removing it. For example, enzymes such as ATP synthase continuously phosphorylate adenosine diphosphate (ADP), converting it into ATP, while enzymes such as kinases dephosphorylate the ATP and convert it back to ADP.
Coenzymes molecules are often vitamins or are made from vitamins. Many coenzymes contain the nucleotide adenosine as part of their structures, such as ATP, coenzyme A and NAD+. This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world.
Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups. This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are the coenzymes.
Each class of group-transfer reaction is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. An example of this are the dehydrogenases that use nicotinamide adenine dinucleotide (NADH) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NAD+ to NADH. This reduced coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.
Coenzymes are therefore continuously recycled as part of metabolism. As an example, the total quantity of ATP in the human body is about 0.1 mole. This ATP is constantly being broken down into ADP, and then converted back into ATP. Thus, at any given time, the total amount of ATP + ADP remains fairly constant. The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily which is around 50 to 75 kg. Typically, a human will use up their body weight of ATP over the course of the day. This means that each ATP molecule is recycled 1000 to 1500 times daily.
|Coenzyme||Vitamin||Additional component||Chemical group(s) transferred||Distribution|
|NAD+ and NADP+||Niacin (B3)||ADP||Electrons||Bacteria, archaea and eukaryotes|
|Coenzyme A||Pantothenic acid (B5)||ADP||Acetyl group and other acyl groups||Bacteria, archaea and eukaryotes|
|Tetrahydrofolic acid||Folic acid (B9)||Glutamate residues||Methyl, formyl, methylene and formimino groups||Bacteria, archaea and eukaryotes|
|Menaquinone||Vitamin K||None||Carbonyl group and electrons||Bacteria, archaea and eukaryotes|
|Ascorbic acid||Vitamin C||None||Electrons||Bacteria, archaea and eukaryotes|
|Coenzyme F420||Riboflavin (B2)||Amino acids||Electrons||Methanogens and some bacteria|
|Coenzyme||Chemical group(s) transferred||Distribution|
|Adenosine triphosphate||Phosphate group||Bacteria, archaea and eukaryotes|
|S-Adenosyl methionine||Methyl group||Bacteria, archaea and eukaryotes|
|3'-Phosphoadenosine-5'-phosphosulfate||Sulfate group||Bacteria, archaea and eukaryotes|
|Coenzyme Q||Electrons||Bacteria, archaea and eukaryotes|
|Tetrahydrobiopterin||Oxygen atom and electrons||Bacteria, archaea and eukaryotes|
|Cytidine triphosphate||Diacylglycerols and lipid head groups||Bacteria, archaea and eukaryotes|
|Nucleotide sugars||Monosaccharides||Bacteria, archaea and eukaryotes|
|Glutathione||Electrons||Some bacteria and most eukaryotes|
|Coenzyme M||Methyl group||Methanogens|
Coenzymes may have been present even earlier in the history of life on Earth. Interestingly, the nucleotide adenosine is present in coenzymes that catalyse many basic metabolic reactions such as methyl, acyl, and phosphoryl group transfer, as well as redox reactions. This ubiquitous chemical scaffold has therefore been proposed to be a remnant of the RNA world, with early ribozymes evolving to bind a restricted set of nucleotides and related compounds. Adenosine-based coenzymes are thought to have acted as interchangeable adaptors that allowed enzymes and ribozymes to bind new coenzymes through small modifications in existing adenosine-binding domains, which had originally evolved to bind a different cofactor. This process of adapting a pre-evolved structure for a novel use is referred to as exaptation.
The functions of coenzymes were at first mysterious, but in 1936, Otto Heinrich Warburg identified the function of NAD+ in hydride transfer. This discovery was followed in the early 1940s by the work of Herman Kalckar, who established the link between the oxidation of sugars and the generation of ATP. This confirmed the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941. Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NAD+ linked metabolic pathways such as the citric acid cycle and the synthesis of ATP.