Cofactor (biochemistry)

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In biochemistry, a cofactor (also cofactor ) is a non-protein component that, in addition to the protein content of a certain enzyme, is essential for its catalytic activity.

The generic term cofactor comprises, in addition inorganic components such as metal - ions different organic molecules which are not of amino acids are designed and altered in enzyme activity. The latter group is summarized under the attack coenzyme ( coenzyme ). In the case of a non-covalent bond, the term cosubstrate (co- substrate ) is often used , while in the case of a firm, more permanent bond the term prosthetic group is used. However, a precise delimitation of the terms is not always given, so that different definitions and classifications can be found by different authors. Cofactors can be roughly divided as follows:

Coenzyme Proesthetic group An organic molecule that is bound with high affinity or covalently to an enzyme; so the prosthetic group cannot dissociate .
Cosubstrate A low molecular weight organic molecule that binds non-covalently to an enzyme and dissociates again after catalysis. During the reaction it accepts or releases chemical groups, protons or electrons, which changes its reactivity. A coenzyme emerges as a cosubstrate - like a prosthetic group - changed from the reaction and must therefore be converted back to its previous state, but this usually does not happen on the enzyme.
Metal ion A metal ion that is bound to an enzyme and required for catalysis is also a cofactor. The corresponding enzyme is called a metalloenzyme .

An enzyme complex with a bound cofactor is called a holoenzyme , without a cofactor an apoenzyme . Compounds that occur ubiquitously , such as water, do not count among the cofactors - and also not among the substrates - although they are often involved in reactions.

Prosthetic groups

How an enzyme with a prosthetic group works

A non-protein component that is firmly (mostly covalently ) bound to a protein and has a catalytic effect is referred to as a prosthetic group (made-up word from ancient Greek προστίθημι 'put in front ') . Since it often emerges changed from the catalysis, it has to be regenerated by the enzyme.

Examples

Coenzymes, cosubstrates

How an enzyme works with coenzyme (cosubstrate)

A cosubstrate or coenzyme is a low molecular weight organic molecule that binds non- covalently to the enzyme and dissociates again after catalysis . During the reaction, it absorbs or releases functional groups , protons, electrons or energy (see also donor-acceptor principle ). So it emerges - like the prosthetic group - changed from the reaction and must therefore be renewed. This also distinguishes the coenzyme from allosteric effectors, for example . Its regeneration typically takes place in a subsequent reaction. Since the coenzyme more like a substrate for acts like an enzyme, it is often more appropriate as co-substrate called.

A common cosubstrate of enzymatically catalyzed reactions is adenosine triphosphate (ATP), from which high-energy phosphate groups (with the formation of ADP or AMP ) can be transferred to other molecules and these can be activated. Some other coenzymes are derivatives of vitamins .

Substance name Coenzyme name Derivative of Function type
Adenosine triphosphate (ATP) - - supplies energy by splitting off a phosphate ,
transfers phosphate to the substrate ( phosphate donor )
Adenosine diphosphate (ADP) - - accepts phosphate from the substrate ( phosphate acceptor )
Nicotinamide Adenine Dinucleotide (NAD) Coenzyme I. - NAD + : electron and proton acceptor, oxidizing agent
NADH: electron and proton donor, reducing agent
Nicotinamide adenine dinucleotide phosphate (NADP) Coenzyme II - NADP + : electron and proton acceptor, oxidizing agent
NADPH: electron and proton donor, reducing agent
Flavin Adenine Dinucleotide (FAD) - Vitamin B 2 FAD: electron and proton acceptor, oxidizing agent
FADH 2 : electron and proton donor, reducing agent
Pyridoxal phosphate - Vitamin B 6
Tetrahydrofolic acid Coenzyme F Vitamin B 9 Methyl group donor
Cobalamins Coenzyme B 12 Vitamin B 12
Ascorbic acid - vitamin C Reducing agent
Coenzyme A Coenzyme A -
Ubiquinone-10 Coenzyme Q 10 -
α-lipoic acid - -

For a complete list of the coenzymes / cofactors recognized by the enzyme commission of the International Union of Biochemistry and Molecular Biology (IUBMB) see the category: Coenzyme .

Examples

Pyridoxal phosphate

Pyridoxal phosphate , activated pyridoxine (vitamin B 6 ), for example, is a coenzyme in the active center of transaminases . Here it catalyzes the deamination of amino acids to alpha - keto acids in the first step (with formation of pyridoxamine phosphate), in the second the transfer of the amino group to another alpha-keto acid (so-called ping-pong-bi-bi mechanism according to Wallace W. Cleland ) . In this case pyridoxal phosphate is regenerated on the enzyme. It is also a coenzyme of decarboxylases , which are used to break down amino acids.

Coenzyme A

Another example is coenzyme A , which is involved in various steps of the citric acid cycle as well as in fatty acid metabolism in free and acetylated form .

FAD, NAD, NADP

The coenzymes flavin-adenine-dinucleotide (FAD) and nicotinamide-adenine-dinucleotide (NAD) serve as electron and proton acceptors or donors in various degradation steps in the citric acid cycle, but also in glycolysis . In this way, they mediate the transfer of electrons from one educt to another. Nicotinamide adenine dinucleotide phosphate (NADP) takes on a comparable role in the opposite direction in building processes such as the biosynthesis of fatty acids . FAD can be covalently linked in some enzymes, it being assumed that this is the case in about 10% of all flavoproteins. An example of this would be succinate dehydrogenase .

Ubiquinone

Another example is the electron carrier ubiquinone , the coenzyme Q in the process of aerobic energy supply, called oxidative phosphorylation . By accepting and releasing electrons or protons, it mediates their transfer between the membrane-bound protein complexes I, II and III of the respiratory chain in the mitochondria .

Metal ions

Ions of metals such as iron (Fe), magnesium (Mg), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) or molybdenum (Mo) are often cofactors of various enzymes. In this role, they become essential trace elements in food that an organism supplies. An enzyme whose active form contains metal ions is called a metalloenzyme . A metal atom can contribute to the stabilization of the protein structure, in the active center it serves to catalyze a certain reaction . If it is crucial for the enzyme function, the lack of the metal can become a limiting factor .

The presence of a zinc cation often indicates its function as a Lewis acid , e.g. B. in peptidases or zinc finger proteins . However, the presence of a certain metal ion can only provide an approximate indication of the function of the enzyme. On the one hand, different enzymes can require the same cofactor. On the other hand, metalloenzymes with a similar function in other species can use a different metal ion. The reason for this is usually the different availability of the respective metals in the living space of the organisms. The Borrelia burgdorferi bacterium, for example, can do without iron because it uses manganese as a cofactor instead. Another example is the use of copper instead of iron for oxygen activation.

Of metalloproteins is when, for example, alkaline earth metals such as calcium and magnesium comfortable on the structure and folding take proteins influence, but do not contribute to a catalytic effect.

Examples

Enzyme inhibition

Substances that are similar to the cofactor in terms of its binding properties and can also complex with the enzyme are competitive inhibitors ; they inhibit the enzyme by competing for the binding site for the cofactor.

See also

Web links

swell

Individual evidence

  1. ↑ Entry on cofactors . In: IUPAC Compendium of Chemical Terminology (the “Gold Book”) . doi : 10.1351 / goldbook.C01128 Version: 2.3.1.
  2. ^ Entry on Coenzymes . In: IUPAC Compendium of Chemical Terminology (the “Gold Book”) . doi : 10.1351 / goldbook.C01126 Version: 2.3.1.
  3. ^ Georg Löffler, Petro E. Petrides and Peter C. Heinrich; Biochemistry and Pathobiochemistry, 8th Edition.
  4. ↑ Dominic PHM Heuts, Nigel S. Scrutton, William S. McIntire, Marco W. Fraaije: What's in a covalent bond ?: On the role and formation of covalently bound flavin cofactors . In: FEBS Journal . tape 276 , no. 13 , June 11, 2009, p. 3405–3427 , doi : 10.1111 / j.1742-4658.2009.07053.x ( wiley.com [accessed September 23, 2019]).
  5. ↑ Martin Mewies, William S. McIntire, Nigel S. Scrutton: Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: The current state of affairs . In: Protein Science . tape 7 , no. 1 , January 1998, pp. 7–21 , doi : 10.1002 / pro.5560070102 , PMID 9514256 , PMC 2143808 (free full text).
  6. ^ Posey JE, Gherardini FC: Lack of a role for iron in the Lyme disease pathogen . In: Science . 288, No. 5471, June 2000, pp. 1651-3. PMID 10834845 .
  7. ↑ T. Ju, RB Goldsmith et al. a .: One protein, two enzymes revisited: a structural entropy switch interconverts the two isoforms of acireductone dioxygenase. In: Journal of molecular biology. Volume 363, number 4, November 2006, pp. 823-834, doi: 10.1016 / j.jmb.2006.08.060 , PMID 16989860 , PMC 1808343 (free full text).