Vitamin K: Features, Forms And Synthesis

Vitamin K belongs to a class of compounds named the terpenoid quinones, isoprene quinones or the prenylquinones. Terpenoids consist of repeating units of isoprene, a 5 carbon isobutane-like structure with at least one carbon-carbon double bond. Quinones consist of benzene or naphthalene rings with two double bonds to oxygen replacing two hydrogens to form 2 carbonyl groups. Terpenoid quinones occur when a quinone is used as a polar head while a terpenoid is used a nonpolar tail. They tend to be found in membrane structure of both cells and organelles owning to their hydrophobic and hydrophilic regions.

Vitamin K is a fat soluble vitamin along with Vitamin A, Vitamin D, and Vitamin E. In humans, Vitamin K is needed for blood clotting and other chemical reactions. Since mammals cannot synthesize Vitamin K naturally, they must get it from outside food sources. There are two types of Vitamin K: K1 and K2. Vitamin K1 is also known as phylloquinone. It is used naturally in plants and other photosynthetic organisms (including cyanobacteria and algae) as in electron acceptor in photosystem I in the chlorplast. Humans receive the K1 form of Vitamin K from spinach, kale and other leafy greens. Vitamin K2 is also known as the menaquinone or more simply MK. MKs are found in archaea, gram positive bacteria as well as other anaerobic types of bacteria. MKs are part of respiration in many of these organisms, acting as the final electron acceptor in place of oxygen.

Humans receive the MK form of Vitamin K from liver, cheeses, as well as a product of the natural microflora of the human gut. The structure of phylloquinone and other MKs is fairly similar. Like all terpenoid quinones, both consist of a polar head region and a nonpolar tail region. The head region consists of a naphthalene ring with the two carbonyl groups as is typical for a quinone. The naphthalene ring also contains a single double bond in the second carbon ring structure as well as a methyl group. The tail region is typically a hydrocarbon structure of singlely bonded carbons as well as isoprene units that varies in length and saturations.

Phylloquinone has only one isoprene unit while the rest of the MKs have more than one isoprene unit. When distinguishing MKs from each other, it is the number of saturations that determine the name. For example MK-4 has 4 unsaturations in its tail (Shearer and Newman 2014). Both forms of Vitamin K are biosynthesized in two separate parts, the head region and the tail region. These two regions come together during a condensation reaction with the assistance of the enzyme DHNA prenyltransferase. The tail regions are formed by the molecules dimethylallyl diphosphate and isopentenyl diphosphate. These precursors for the tail region are formed by the mevalonate (MVA) and 1- deoxy-D-xylulose-5-phosphate (DXP) pathways. The MVA pathway is favored by acrchea while the DXP pathway is favored by bacteria. However, there are some species such as Streptomycetes that are capable of preforming either pathway. The head region is formed by the molecule, 4-dihydroxy-2- naphthoate (DHNA). This precursor is formed from a molecule chorismite which is produced in the Shikimate pathway.

Another type of isoprene quinone is ubiquinone (UB) or coenzyme Q (CoQ). It is found in all eukaryotic species as the sole quinone, as well as being the sole quinone in aerobic bacteria. Anaerobic bacteria have ubiquinone but also have menaquinone, naphthoquinones and other types of quinones. Archea are one of the only organisms in which ubiquinone is not present. In cells, ubiquinone is used as electron transporter in the mitochondria of the electron transport chain. In bacterial cells that lack a mitochondira, ubiquinone is still used to generate energy but is instead found in the plasma membrane of the cell. It can interchange between three redox states: fully oxidized, partially reduced and fully reduced. Ubiquinone’s ability to reversibly change between these three states allow it to be an efficient electron carrier. Ubiquinone is considered to be a benzoquinone, which is type of isoprene quinone whose head area is a benzene like ring. It has two carbonyl oxygens as is typical of a quinone but also has a methyl and two ethers attached to the ring structure. The side chain or tail region of ubiquinone consists of repeating isoprene units. The number of times the unit repeats is dependent on the species. For example, Gluconobacter suboxydans and humans have 10 units, E. Coli has 8 units and yeast has 6 units. Plants typically have between 8-10 units.

Despite ubiquinone’s similar appearance to vitamin K, it is not considered to be a vitamin itself because it can be synthesized in the mammalian body through the essential amino acid tyrosine. Ubiquionone has a very short half-life (approximately 30 hours in spinach) and therefore is continuously synthesized by the cell. Ubiquinone synthesise is quite complicated and involves many steps, each requiring a specific enzyme and thus a specific gene. In bacteria, a set of 8 genes named ubiA-ubiH have all been linked to a specific enzyme for a specific step in the formation of ubiquinone while in plant cells more than 35 enzymes have been identified in ubiquinone formation. Ubiquinone is synthesized in several different ways depending on the species. In bacteria, chorismite is used as the precursor for the head. It is produced through the shikimate pathway. As animals are unable to use the shikimate pathway, in eukaryotes, the amino acid tyrosine is used as a precursor for the head. Yeast must first convert chorismite to tyrosine before being able to synthesize the head. From either the chorismite or the tyrosine, 4-hydroxybenzoic acid (4HB) is produce as an intermediate. This is then modified to create the final head component of ubiquinone. For example, both prokaryotic and eukaryotic cells add three methyl groups on the head from S-adenosylmethionine (SAM). In bacteria, the side chains are made in the 1-deoxy-D-xylulose 5-phosphate pathway from pyruvate and glyceraldehyde 3-phosphate (G3P). In eukaryotes, the side chains are made from acetate in the mevalonate pathway (MVA). Plants are also able to use pyruvate and G3P as the precursor to their side chains. From either acetate, pyruvate or G3P, cells create isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) which are the intermediates that are used to create the isoprene side chains. Much like in the two forms of vitamin K, the final step involves bringing together the head and the side tail in a condensation reaction.

A third type of isoprene quinone is plastoquinone (PQ). It is found in plant cells, particularly in the thylakoid stacks of chloroplasts. Plastoquinone is found in photosystem II (PSII) and, like other isoprene quinones discussed, it is an electron carrier. It moves electrons from PSII to the cytochrome during photosynthesis. Plastoquinone is also used as an effector for carotenoid biosynthesis. As with other isoprene quinones, plastoquinone consists of a head region and a tail region. Plastoquinone considered to be another benzoquinone and has a structure very similar to ubiquinone. It has a 6 carbon ring structure with two methyl groups as well as two carbonyl groups on the ring. Its tail is a repeating isoprene unit between 9 and 10 units long.

Biosynthesis of plastoquinone is nearly identical to the biosynthesis of ubiquinone. The precursor for the head region is also tyrosine, though it gets converted to homogentisic acid (HGA) as opposed to hydroxybenzoic acid (4HB), The side chains of plastoquinone come from either G3P and pyruvate through the 2-C-methyl-D-erythritol 4-phosphate pathway (MEP) or acetyl-CoA through the mevalonate pathway (MVA). Similar to ubiquinone, these precursor are then turned into IPP and DMAPP which eventually form the side chains. Solanesyl diphosphate (SPP) is used as an additional intermediate for the side chain tails in plastoquinones. As for all isoprene quinones, the final step is the condensation of the head and tail regions to form one molecule. Isoprene quinones are an interesting group of molecules. Their precursor in prokaryotes come from the shikimate pathway. Isoprene quinones are a prime example in biology of structure fitting function. Their structure of a hydrophobic and hydrophilic region allow them to be embedded into membranes. Their structure also allows them to be found in 3 redox-sates. This then fits their function of acting as electron carriers in the membranes of energy producing organelles in eukaryotic cells and cell membranes of prokaryotic cells.