What Are Flavoproteins and What Is Their Function?

Flavoproteins represent a widespread class of proteins present in all domains of life. These proteins are defined by their association with a flavin-based molecule, a derivative of a nucleic acid. Their discovery dates back to 1879 when a bright-yellow pigment was isolated from cow’s milk, initially named lactochrome. By the 1930s, this pigment was identified as a component of the vitamin B complex and later named riboflavin. Flavoproteins participate in a wide range of biological activities, from energy metabolism to DNA repair.

Unpacking Flavoproteins: The Protein-Flavin Partnership

Flavoproteins are composite structures, each consisting of a protein component, known as the apoprotein, and a non-protein group called a flavin cofactor. The two main flavin cofactors are Flavin Adenine Dinucleotide (FAD) and Flavin Mononucleotide (FMN). Both of these molecules are synthesized in organisms from riboflavin, also known as vitamin B2, which many eukaryotes, including humans, must obtain from their diet.

The synthesis process involves enzymes that first add a phosphate group to riboflavin to create FMN. Subsequently, an adenine nucleotide is attached to FMN to form FAD. The resulting FAD or FMN cofactor binds to its specific apoprotein, creating the functional flavoprotein. This binding can be either a tight, non-covalent interaction or a more permanent covalent bond, with the latter accounting for about 5-10% of flavoproteins.

The Workhorses of the Cell: Flavoprotein Functions

The primary role of most flavoproteins is to catalyze oxidation-reduction (redox) reactions, where they act as electron carriers. The flavin’s isoalloxazine ring system can accept and donate electrons in a stepwise fashion, handling either one or two electrons at a time. This versatility allows flavoproteins to mediate electron flow between molecules that can only handle two-electron transfers and those that manage single-electron transfers.

This electron-carrying capacity is observable in cellular respiration, where flavoproteins are parts of the electron transport chain in mitochondria. For example, the enzyme succinate dehydrogenase uses a covalently bound FAD to transfer high-energy electrons during the breakdown of succinate. Similarly, flavoproteins are involved in the metabolism of fatty acids and amino acids, helping to process these molecules for energy. Beyond metabolism, some flavoproteins have highly specialized roles. Photolyases use their flavin cofactor to absorb light energy and repair UV-damaged DNA, while cryptochromes act as blue-light photoreceptors that regulate processes like circadian rhythms in animals and development in plants.

Flavoproteins in Nature’s Blueprint

The presence of flavoproteins extends across the entire tree of life, with tailored roles in different organisms. In some bacteria, flavoproteins are involved in generating light through bioluminescence. Certain pathogenic bacteria, like Vibrio cholerae, even utilize riboflavin directly as a cofactor in a sodium-pumping enzyme, a rare exception to the FAD or FMN rule. In plants, flavoproteins are not only part of the photosynthetic machinery that captures light energy but also participate in processes like nitrate assimilation and the synthesis of plant hormones.

In animals and humans, flavoproteins are abundant in mitochondria. The human genome encodes for 90 distinct flavoproteins, with about 84% using FAD and 16% using FMN. These enzymes include monoamine oxidases, which are involved in breaking down neurotransmitters like serotonin and dopamine. Others, such as cytochrome P450 reductase, are situated in the endoplasmic reticulum and participate in the metabolism of drugs and the synthesis of steroid hormones.

Cellular Processes Fueled by Flavoproteins

Their central role in redox reactions is directly linked to the production of adenosine triphosphate (ATP), the main energy currency of the cell. By facilitating electron transfer in the mitochondrial respiratory chain, flavoproteins help create the proton gradient that drives ATP synthesis. This constant electron transfer also helps maintain metabolic homeostasis. Flavoproteins contribute to protecting the cell from oxidative stress by neutralizing reactive oxygen species. For instance, the flavoprotein glutathione reductase helps regenerate an antioxidant molecule, glutathione.