Some enzymes do not need any additional components to show full activity.

However, others require non-protein molecules called cofactors to be bound for activity

Cofactors
~ Cofactors are often classified as inorganic substances that are required for, or increase the rate of, catalysis. ~ generally a metal ion which is bound to a protein or enzyme which helps perform catalysis of the enzyme or protein. ~ A substance, such as a metallic ion or coenzyme, that must be associated with an enzyme for the enzyme to function. ~ is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes. ~ can be considered "helper molecules" that assist in biochemical transformations. ~ can also be classified depending on how tightly they bind to an enzyme, with loosely-bound cofactors termed coenzymes tightly-bound cofactors termed prosthetic groups

Some enzymes complexes require several cofactors:

ex.

multienzyme complex pyruvate dehydrogenase = requires five organic cofactors and one metal ion

Classifictaion:
(Cofactors can be divided into two broad groups)

Organic cofactors
~ such as flavin or heme ~ Organic cofactors are often vitamins or are made from vitamins. ~ Organic cofactors are sometimes further divided into:

coenzymes

= small organic molecules that transport chemical groups from one enzyme to another.[ = refers specifically to enzymes and as such to the functional properties of a protein = coenzymes are organic molecules that are required by certain enzymes to carry out catalysis. = They bind to the active site of the enzyme and participate in catalysis but are not considered substrates of the reaction. = may undergo reduction while attached to one apoenzyme, and then migrate to another apoenzyme where it can be oxidized = are of low molecular weight (around 500) and are heat stable. = is an organic compound bound the enzyme which helps in transfer of a group or an atom

= proteins that bind to an enzyme to "activate" it, allowing it to do its job. = are chemically changed as a consequence of enzyme action, it is usefulto consider coenzymes to be a special class of substrates, or second substrates, which arecommon to many different enzymes.

holozyme = An enzyme and a coenzyme together form an enzymatically active conjugated protein The major coenzymes of dehydrogenases are the two dinucleotides
-

NAD NADP

Note: most enzymes do not require a coenzyme. - Apoenzyme = inactive enzyme, without the cofactor = Without its respective coenzyme = The enzyme (protein) component of the holozyme - Holoenzyme = complete enzyme with cofactor = With the coenzyme Precursors of coenzymes: B VITAMINS
o o o

thiamine (B1) riboflavin (B2) nicotinamide

coenzymes in group transfer reactions coenzyme nicotine adenine dinucelotide nicotine adenine dinucelotide phosphate flavine adenine dinucelotide coenzyme A coenzymeQ thiamine pyrophosphate pyridoxal phosphate biotin carbamide coenzymes abbreviation NAD - partly composed of niacin NADP -Partly composed of niacin FAD - Partly composed of riboflavin (vit. B2) CoA CoQ thiamine (vit. B1) pyridoxine (vit B6) Biotin vit. B12 entity transfered electron (hydrogen atom) electron (hydrogen atom) electron (hydrogen atom)

Acyl groups electrons (hydrogen atom) aldehydes amino groups carbon dioxide alkyl groups

 prosthetic groups = emphasizes the nature of the binding of a cofactor to a protein (tight or covalent) and thus refers to a structural property. = Non protein coenzyme component = remains attached to the apoenzyme while undergoing oxidation and reduction. (Holozyme = Apoenzyme + Prosthetic Group)

Inorganic cofactors
~ such as the metal ions Mg2+, Cu+, Mn2+ or iron-sulfur clusters

metal ions

= are common cofactors In some cases enzymes may be activated by simple substances like metal ions which are then called activators. The substrate forms, a complex with the metal ion and then reacts with the enzyme. Examples of metal ions which function as cofactors are Na+, K+, Ca++ Co++, Mg++, Mn++, Cd++, Fe++, Cr+++ and Al+++.

Examples of some enzymes that require metal ions as cofactors is shown in the table below cofactor Zn++ Zn++ Fe+++ or Fe++ Fe+++ or Fe++ Cu++ or Cu+ K+ and Mg++ enzyme or protein carbonic anhydrase alcohol dehydrogenase cytochromes, hemoglobin ferredoxin cytochrome oxidase pyruvate phosphokinase

Iron-sulfur clusters
= complexes of iron and sulfur atoms held within proteins by cysteinyl residues = they play both structural and functional roles, including electron transfer, redox sensing, and as structural modules

In many cases, the cofactor includes both an inorganic and organic component. One diverse set of examples are the haem proteins, which consists of a porphyrin ring coordinated to iron.
Ion Cupric Examples of enzymes containing this ion Cytochrome oxidase Catalase Cytochrome (via Heme) Nitrogenase Hydrogenase Glucose 6-phosphatase Hexokinase Arginase Nitrate reductase Urease Glutathione peroxidase Alcohol dehydrogenase Carbonic anhydrase DNA polymerase

Ferrous or Ferric

Magnesium Manganese Molybdenum Nickel Selenium

Zinc

Vitamins and derivatives Additional Chemical componen group(s) t transferred

Cofactor Vitamin

Distribution

Thiamine Thiamine pyrophosp None (B1) hate NAD+ and Niacin (B3 ADP NADP+ ) Pyridoxal Pyridoxin phosphate None e (B6)

2-carbon groups, Bacteria, archaea a cleavage nd eukaryotes

Electrons

Bacteria, archaea a nd eukaryotes

Amino and carboxyl groups

Bacteria, archaea a nd eukaryotes

Lipoamide Lipoic acid Methylcob Vitamin alamin B12

None

electrons, acyl groups

Bacteria, archaea a nd eukaryotes Bacteria, archaea a nd eukaryotes Bacteria, archaea a nd eukaryotes Bacteria, archaea a nd eukaryotes

Methyl group

acyl groups

Cobalami Cobalami None ne ne (B12)

hydrogen, alkyl groups

Biotin

Biotin (H) None

CO2

Pantothe Coenzym nic ADP eA acid (B5)

Acetyl group and Bacteria, archaea a other acyl groups nd eukaryotes

Tetrahydr Folic ofolic acid acid (B9)

Methyl, formyl, m Glutamate Bacteria, archaea a ethylene and residues nd eukaryotes formimino groups Carbonyl Bacteria, archaea a group and electro nd eukaryotes ns Bacteria, archaea a nd eukaryotes

Menaquin Vitamin K None one

Ascorbic acid

Vitamin C None

Electrons

Flavin Riboflavin mononucl None (B2) eotide Flavin adenine Riboflavin None dinucleoti (B2) de Coenzym Riboflavin Amino e F420 (B2) acids

Electrons

Bacteria, archaea a nd eukaryotes

Electrons

Bacteria, archaea a nd eukaryotes

Electrons

Methanogens and some bacteria

Non-vitamins Chemical group(s) transferred Phosphate group

Cofactor

Distribution

Adenosine triphosphate S-Adenosyl methionine Coenzyme B Coenzyme M

Bacteria, archaea and eukar yotes Bacteria, archaea and eukar yotes Methanogens Methanogens Bacteria, archaea and eukar yotes

Methyl group

Electrons Methyl group

Coenzyme Q

Electrons

Diacylglycerols a Bacteria, archaea and eukar Cytidine triphosphate nd lipid head yotes groups Some bacteria and most eukaryotes Bacteria, archaea and eukar yotes

Glutathione

Electrons

Heme

Electrons

Methanofuran

Formyl group

Methanogens Bacteria, archaea and eukar yotes

Molybdopterin

Oxygen atoms

Nucleotide sugars

Monosaccharide Bacteria, archaea and eukar s yotes Bacteria, archaea and eukar yotes

3'-PhosphoadenosineSulfate group 5'-phosphosulfate Pyrroloquinoline quinone

Electrons

Bacteria

Tetrahydrobiopterin

Oxygen atom and electrons

Bacteria, archaea and eukar yotes

Tetrahydromethanopt Methyl group erin

Methanogens

Cofactors as metabolic intermediates

= 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 loosely-bound organic cofactors, often called coenzymes. = Each class of group-transfer reaction is carried out by a particular cofactor, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. Nucleotides = may also function as coenzymes in certain metabolic reactions.

Non-enzymatic cofactors
The term is used in other areas of biology to refer more broadly to non-protein (or even protein) molecules that either activate, inhibit or are required for the protein to function. For example: Cofactors or coactivators = ligands such as hormones that bind to and activate receptor proteins. Corepressors = while molecules that inhibit receptor proteins are termed corepressors.