Travis
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- Jul 14, 2016
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I just read some studies on vitamin K. It's more surprising than you might think:
Back in the 1960's, it was found that phylloquinone could convert into MK-4 in birds. This was speculated to be a consequence of intestinal bacteria. It was also found out with a radioactive ¹⁴C-labeled phytyl chain that the entire original "tail" was removed in this process.
To test if bacteria was actually responsible for the vitamin K₁ ⇨ K₂ conversion, studies were undertaken with sterilized, germ-free rats:
There is a break in the ordinate in the second graph.
Notice the similar distribution (hatched bars). The same dose of phylloquinone produces essentially the same tissue concentrations as an equivalent dose of menadione, the vitamin K "head". Vitamin K₁ has the same capacity to produce MK-4 as menadione. This also proves that bacteria are not involved.
So what about people?
Doses of phylloquinone were given to humans while the menadione levels in their urine was measured. Menadione is just the "head" of the molecule and lacks any tail whatsoever.
The hepatic and pancreatic cells were most efficient at making the conversion, followed by kidney and muscle cells.
And like Masterjohn mentioned, the gene that isoprenylates the menadione to form MK-4 has been determined. To find it, these researchers looked for similarities to other known enzymes responsible for doing this in bacteria. You would also expect similarities to the enzyme that makes coenzyme Q₁₀...
They proved that this was the specific gene by measuring the synthesis rates in the presence, and absence, of a small interfering piece of RNA. The interfering RNA matches the mRNA that produces the enzyme, hybridizes with it, and permanently inactivates it.
You can see MK-4 synthesis in the cell without the small interfering RNA sequence for the putative vitamin MK-4 gene (UBIAD1). In the presence of the siRNA, the synthesis stops. Mismatching siRNA strands had no effect. The one on the right is for the mRNA encoding the coenzyme Q prenyltransferase (COQ2) enzyme, proving that the CoQ₁₀-producing enzyme is not responsible despite their similarities.
It's official. We can make the coveted K₁ ⇨ K₂ conversion.
Based on these studies, I get the impression that vitamin K₁ is sufficiently effective at producing MK-4. The menadione head appears to be split-off during digestion and then transfers inside the liver, pancreas, and blood vessel cells to become MK-4.
Ronden, Jacintha E., et al. "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat." Biochimica et Biophysica Acta (BBA)-General Subjects 1379.1 (1998): 69-75.
Thijssen, Henk HW, et al. "Menadione is a metabolite of oral vitamin K." British journal of nutrition 95.2 (2006): 260-266.
Nakagawa, Kimie, et al. "Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme." Nature 468.7320 (2010): 117.
Back in the 1960's, it was found that phylloquinone could convert into MK-4 in birds. This was speculated to be a consequence of intestinal bacteria. It was also found out with a radioactive ¹⁴C-labeled phytyl chain that the entire original "tail" was removed in this process.
To test if bacteria was actually responsible for the vitamin K₁ ⇨ K₂ conversion, studies were undertaken with sterilized, germ-free rats:
The MK-4 tissue distribution pattern after phylloquinone intake was comparable with that found after menadione intake.
There is a break in the ordinate in the second graph.
Notice the similar distribution (hatched bars). The same dose of phylloquinone produces essentially the same tissue concentrations as an equivalent dose of menadione, the vitamin K "head". Vitamin K₁ has the same capacity to produce MK-4 as menadione. This also proves that bacteria are not involved.
So what about people?
Doses of phylloquinone were given to humans while the menadione levels in their urine was measured. Menadione is just the "head" of the molecule and lacks any tail whatsoever.
The results were nearly identical. They also measured intravenously-administered phylloquinone with no results, so the "tail" must be cleaved-off in the intestines while the menaquinone "head" then travels throughout the body. They then measured the ability of certain cell lines to turn menadinone into MK-4:In summary, the present study shows that menadione is a product of vitamin K catabolism, both of phylloquinone as well as menaquinones.
The hepatic and pancreatic cells were most efficient at making the conversion, followed by kidney and muscle cells.
And like Masterjohn mentioned, the gene that isoprenylates the menadione to form MK-4 has been determined. To find it, these researchers looked for similarities to other known enzymes responsible for doing this in bacteria. You would also expect similarities to the enzyme that makes coenzyme Q₁₀...
They proved that this was the specific gene by measuring the synthesis rates in the presence, and absence, of a small interfering piece of RNA. The interfering RNA matches the mRNA that produces the enzyme, hybridizes with it, and permanently inactivates it.
Stealth siRNA siCOQ2 is a 25-bp duplex oligoribonucleotide with a sense strand corresponding to nucleotides 1016–1040 of the reported human COQ2 mRNA sequence.
You can see MK-4 synthesis in the cell without the small interfering RNA sequence for the putative vitamin MK-4 gene (UBIAD1). In the presence of the siRNA, the synthesis stops. Mismatching siRNA strands had no effect. The one on the right is for the mRNA encoding the coenzyme Q prenyltransferase (COQ2) enzyme, proving that the CoQ₁₀-producing enzyme is not responsible despite their similarities.
It's official. We can make the coveted K₁ ⇨ K₂ conversion.
Based on these studies, I get the impression that vitamin K₁ is sufficiently effective at producing MK-4. The menadione head appears to be split-off during digestion and then transfers inside the liver, pancreas, and blood vessel cells to become MK-4.
Ronden, Jacintha E., et al. "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat." Biochimica et Biophysica Acta (BBA)-General Subjects 1379.1 (1998): 69-75.
Thijssen, Henk HW, et al. "Menadione is a metabolite of oral vitamin K." British journal of nutrition 95.2 (2006): 260-266.
Nakagawa, Kimie, et al. "Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme." Nature 468.7320 (2010): 117.
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