**3. Vitamin K in humans**

by bacteria of the intestine. However, no direct evidence can be established for the biological effects of menaquinones in humans; however, it is surmised that menaquinones mainly are utilized in the synthesis of blood‐clotting factors upon the depletion of phylloquinone [2]. Additionally, menaquinones have proven to be more efficient than phylloquinone as a bioactive molecule in processes such as osteroclast differentiation, lowering of blood cholesterol levels,

The menaquinones have proven to be important in several biological reactions, for example electron transport, active transport, oxidative phosphorylation, as well as endospore formation in bacteria. Furthermore, variations in the inherent molecular structures of the menaquinones and their skewed distributions among bacterial strains are considered as an important marker in bacterial taxonomy [3]. The biosynthesis of menaquinone has been subject to considerable attention in the quest for drug targets displaying multidrug resistance toward Gram‐positive

There are two naturally occurring forms of vitamin K. Plants and some cyanobacteria synthe‐ size phylloquinone, which is also known as vitamin K1. Bacteria synthesize a range of vitamin K, but not vitamin K1, using the different lipophilic side chains derived from isoprene (5‐ carbon) units. Bacterial vitamin K(s) are designated menaquinone‐n (MK‐n), where "n" stands for the number of isoprenoid (5‐carbon) units. Vitamin K1 and K2 share the common molecular structure, belonging to the 2‐methyl‐1,4‐naphthoquinone system, and they appear to be differ structurally in their number of isoprene units within their side chain, as well as their degree of unsaturation [4] (**Figure 1**). Menaquinones, displaying side chains containing up to 15 isoprene units have been identified. For instance, MK‐8 is predominantly seen in *E. coli,* while *M. tuberculosis* mainly utilizes MK‐9 as the preferred electron carrier. The menaquinones, which possess from 2 to 13 isoprene units, have been detected in both human and animal tissues. A plethora of synthetic vitamin K(s) are now commercially available, and biochemically fabri‐ cated vitamin K(s), in the form of vitamin K3, K4, and K5, are applied in several areas, which

include pet food industry (e.g., VK3), as well as human supplements (e.g., VK5).

**Figure 1.** Structures of vitamin K1 and K2 and synthetic vitamin Ks (vitamin K3, K4, and K5).

as well as the slowing down of atherosclerotic progression.

282 Vitamin K2 - Vital for Health and Wellbeing

pathogenic microorganisms, including *Mycobacterium tuberculosis*.

**2. Vitamin K: general molecular structures**

The role of vitamin K as a cofactor in blood coagulation stems from the post‐translational modification of a number of plasma proteins such as factors II, VII, IX, X, proteins C, S, Gla (γ‐carboxyglutamic acid) proteins has been well‐documented. In addition to the essential role of vitamin K in the blood‐clotting cascade, the potential role in the increase of bone mass [5, 6], antioxidant mechanisms [7], the biosynthesis of cholesterol and steroid hormones [8], and anticancer effects have been reported [9, 10].

Vitamin K is taken up by organs such as the liver and bones, but abundantly distributed in other organs such as the brain, the kidneys, and gonadal tissues [11]. However, the exact role of vitamin K in the present tissues is not well described. The distribution of vitamin K moieties is varying, which depends on the molecular structure of the side chain. As for humans, vitamin K1 is distributed to all tissues and organs, with relatively large amounts to the liver, the heart, and the pancreas (some 10.6, 9.3, 28.4 pmol/g wet tissue weight, respectively). However, low levels (<2 pmol/g) were measured in the brain, kidney, and lung tissue speci‐ mens. Menaquinone‐4 (MK‐4) also seems to be distributed to a plethora of other tissues, that is, its levels exceed the levels of vitamin K1 detected in the brain and kidneys (2.8 ng/g), which equals to that found in the pancreas. However, some organs, such as the liver, heart, and lung remain low in terms of MK‐4 contents. The less known MK‐6 ∼ 11 menaquinone species are also found in the liver, while only small amounts of MK‐6 ∼ 9 are detected in organs such as the heart and pancreas. Finally, the total amount of vitamin K reported in human plasma was in the range of 0.47 ∼ 1.19 nmol/L [1, 12].

Vitamin K can be absorbed well from diet; however, total vitamin K levels are depend greatly on the gut or digestive health. The intestinal bacteria (i.e., microbiota) influence human nutrition and metabolism in diverse ways. The gut microbiota produces menaquinone; thus, it is considered that vitamin K deficiency is quite rare for healthy humans. In addition, the vitamin K1 is absolutely abundant in leafy and salad vegetables, and herbs. It is easy to understand that newborn babies are born with a vitamin K deficiency, giving newborns a vitamin K injection upon birth or oral vitamin K drops is established to prevent bleeding or a hemorrhagic disease development. In general, vitamin K deficiency results from extremely inadequate intake of fat (malabsorption) or use of coumarin anticoagulants.
