MULTIPLE SCLEROSIS

The Ubiquitous Co-Enzyme UDPGlucuronic Acid

Detoxifying Agent in Kombucha Tea ?

By Norbert Hoffmann

Glucuronic acid is considered by many to be one of the important key components found in Kombucha Tea because of its detoxifying action. It is widely distributed in plants, found in gums, mucilages, saponines etc. and in animals. The related compound, UDPGlucuronic acid which is the active or co-enzyme form of Glucuronic acid, has been discovered in several non-Kombucha bacteria by at least eight scientists (Dutton, 1980). Since metabolic processes in related organisms are generally similar, it can, therefore, be expected that UDP-Glucuronic acid is also present in the Kombucha bacteria. This, of course, still has to be substantiated. It is this compound which binds toxins in the body and allows their elimination. Dutton (1966) states that "the biosynthesis of the simple conjugates of Glucuronic acid was shown to occur, somewhat ironically, ... by glucuronyl transference from an 'active' form, UDP (uridine diphosphate)-Glucuronic acid, and (it was) demonstrated that this nucleotide was derived, in animals, not from glucuronate, but from glucose by way of UDP-glucose."

The Detoxification Process

UDP-Glucuronic acid is formed in the liver of all animals including primates and conjugates (combines with) poisonous substances making them more water-soluble to allow for subsequent elimination. This binding of poisonous compounds is catalyzed by the enzyme UDP-Glucuronyltransferase which has been found in all major body organs, heart, kidneys, adrenal gland, spleen, thymus etc.

Another enzyme, Glucuronidase, works the opposite way. It can break the conjugated substances (glucuronides) apart again to free hormones and other chemicals where they are needed. It is controlled by a substance called Saccharolactone which can inhibit its action. In addition, naturally occurring bacteria in the intestines use this enzyme to break down some of the glucuronides into its components, allowing reabsorption of Glucuronic acid and the conjugated substance (toxin or drug) provided it is lipid soluble, through the intestinal walls. This explains why certain drugs normally excreted with feces remain in the body longer than anticipated, for example glutethimide (Doriden) and phenolpthalein. Toxins with smaller molecules normally are excreted with urine thus escaping biotransformation by bacterial enzymes. (Levine, 1978).

UDP-Glucuronic Acid Functions

UDP-Glucuronic acid has three major functions:

Chemical Compounds and How They Relate

Glucuronic acid has been found in Kombucha Tea by several researchers in the past, while more recent research conducted by a lab commissioned by Michael Roussin was not able to substantiate earlier findings. This unexpected outcome led me to take a closer look at the Glucuronic acid pathway and the compounds involved. I made several interesting discoveries:

1. According to a post on the internet, a lab commissioned by Michael Roussin found Saccharic-acid-1,4 lactone, which is also called d-Glucaro-1,4-lactone or Saccharolactone. d-Glucaro-y-lactone is actually part of the Glucuronic acid pathway. It is a derivative of d-Glucurono-y-lactone which in turn comes from UDP-Glucuronic acid or Glucuronic acid depending on which way you go around the pathway circle shown in figure 1 below. (Note: the letters d and y - actually gamma - refer to the three-dimensional molecular structure of a compound; the numbers 1,4 indicate the carbon atoms in a ring structure where specific sub-parts are attached to the molecule.)
2. Michael Roussin's post lists another compound, Saccharic acid, also called Glucaric acid. A related chemical, it is derived via intermediate steps from UDP-Glucuronic acid and represents the end-product of one of the "side arms" of the Glucuronic acid pathway (see figure 1).
3. The compound directly involved in detoxification is UDP-Glucuronic acid and not Glucuronic acid. UDP stands for Uridine-diphosphate, a phosphorilated derivative of the nucleotide Uridine found in RNA (not DNA). It is synthesized from UDP-glucose, the active form of glucose. UDP-Glucuronic acid can therefore be considered the active or co-enzyme form of Glucuronic acid.
4. The synthesis of Ascorbic acid represents another "side arm" of the Glucuronic acid pathway branching off from Glucuronic acid followed by several additional steps before the end product, Ascorbic acid, is reached.

What about Enzymes?

Enzymes very specific to the individual compounds being acted upon catalyze each one of the many steps involved in biosynthesis. There are thousands of enzymes at work in animal and plant metabolism. Enzymes are not changed as a result of these processes and remain viable for a long time. They can be turned off or on by other compounds, elements, or vitamins acting as co-enzymes. Sometimes they can be activated or de-activated by products coming from the same metabolic pathway in which they are involved. This represents a feedback mechanism regulating the amount of compounds being produced similar to the thermostat in our house controlling temperature. In addition to the catalytic function provided by enzymes, energy input may be required for the synthesis of compounds. Usually this energy is supplied by ATP (Adenosine Triphosphate), sometimes by GTP (Guanine Triphosphate) or UTP (Uridine Triphosphate) etc. While most of the enzymes are found inside of microorganism cells, some of them may also be found outside. Among them are the ones required to break down food molecules, for example sugar or amino acids. In my research of Kombucha Tea I discovered the presence of a significant amount of protein. This may actually represent enzymes excreted by the Kombucha microorganisms in order to cleave the table sugar into its simpler components which then can enter the cell walls (see protein research).

Indicators for Compounds in Glucuronic Acid Pathway

As can be seen in figure 1 below, the various compounds found by the different researchers so far are all part of the same pathway. Generally, presence of one of the compounds can be taken as indication that the other compounds will be present also. For example, presence of Saccharic acid (Glucaric acid) would indicate that Saccharolactone (Glucaro-lactone); Glucurono-lactone and UDP-Glucuronic acid are most likely also present. Furthermore, many of the steps in the Glucuronic acid and other metabolic pathways are reversible under certain conditions.

Explanation for Presence of Various Chemical Compounds?

I found an interesting statement in a scientific publication (Schlegel, 1985). He said that large quantities of intermediate compounds found in solutions actually represent an over-production by yeasts caused by the availability of excessive quantities of carbohydrates and frequently by insufficient amounts of trace elements. This condition leads to a disorganization of the metabolism and a backing up of these intermediates. I assume that this also applies to bacteria and may explain the presence of some of the compounds that have been found in Kombucha Tea. In nature, Schlegel continues, one never finds any significant secretion of intermediate chemical products. The small quantities of available nutrients are always completely metabolized.

To be or not to be .. there

While several researchers have confirmed the presence of Glucuronic acid in the K.T. solution, a lab commissioned by Michael Roussin (1996) was not able to confirm this finding. Tests for UDP-Glucuronic acid also turned out to be negative. (http://www.geocities.com/mikeroussin).

The findings published by Michael Roussin, however, cannot be considered conclusive for the entire Kombucha culture. UDP-Glucuronic acid, as can be seen in the metabolic pathway diagram below, is an intermediate metabolite and as such should under normal circumstances not be present outside of bacterial cells. Generally, only end products of an incomplete oxidation are found in solution, for example alcohol, vinegar, and a number of organic acids. In addition, as explained above, various enzymes may be excreted to break down food molecules like sugar or amino acids. Scientists have to this day not been able to completely explain the function of vitamins or antibiotics that also can be found outside of cells. The transport of intermediate metabolites like UDP-Glucuronic acid across cell walls would have no function for the cell and would consume too much energy.

There is, however, one exception: Intermediate metabolites may be transported across cell walls into the solution if there is too much of it. Two reasons can account for this condition: 1. There is a "malfunction" and enzymes involved in the next metabolic step are not breaking down the metabolite sufficiently because of inhibition or other causes. 2. There is an excess of nutrients entering the metabolic pathway. (Johnson, 1997 and Schlegel, 1985 - also see above "Explanation of Various Compounds….")

These considerations offer an excellent explanation why some scientists - depending on differences in conditions - have found Glucuronic acid while others have not. First breaking down (lysing) the microorganisms and possibly using a centrifuge for component separation before performing analytical tests could show the presence of Glucuronic or UDP-Glucuronic acid inside of bacteria.

Conjugation with Acetic Acid ?

Acetic acid or vinegar is one of the major components of Kombucha Tea found in significant quantities. According to the detoxification research (Dutton, 1980), acetic acid is another compound capable of conjugation with toxins making them more soluble for subsquent elimination from the body. It is quite possible that it is the vinegar in Kombucha Tea - rather than glucuronic acid - that provides most of its detoxification benefits. I might mention here that apple cider vinegar is a popular folk medicine used because of its beneficial effects - probably including detoxification through conjugation of toxins.

Kombucha Bacteria - Medicinal Capsules?

Since most of the compounds produced by the Kombucha bacteria remain inside of the cell, they could be compared to medicinal capsules. This idea was suggested to me by Dr. Ted Johnson, a biology professor at St. Olaf College in Northfield, Minnesota. Once ingested, many of these "capsules" may pass the stomach intact to be broken down in the intestines and then - and only then - any beneficial compounds found inside become available to do their work. Other chemicals in the tea solution itself become available somewhat faster. All of them work together to detoxify and strengthen our body.

Sources:

Blanc P. Research on tea fungus. Draft of research article posted to Kombucha Discussion List. Nov. 9, 1995.

Encyclopedia of chemical technology, John Wiley. New York. 1978

Johnson, Ted. PhD. St. Olaf College, Northfield, MN. Personal conversation, June 2, 1997.

Levine, R. Pharmmocology: Drug actions and reactions. Little, Brown and Co., Boston. 1978.

McGraw Hill Encyclopedia of science and technology. 7th ed. McGraw Hill. New York. 1992.

Dutton G. Glucuronidation of drugs and other compounds.CRC Press. Boca Raton. 1980.

Dutton G. Ed. Glucuronic acid, free and combined: chemistry, biochemistry, pharmocology, and medicine. Academic Press. New York. 1966.

Dictionary of organic compounds. 5th ed. Chapman and Hall. New York. 1988.

Hawk's Physiological chemistry. Ed. Oser B. 14th ed. McGraw Hill. New York. 1965.

Henschen A. et. al., ed. High performance liquid chromatography in biochemistry. VCH Verlagsgesellschaft. Weinheim. 1985.

Roussin M. Out on the kombucha range. Post to Kombucha Discussion List. Personal Repeat of e-mail: May 6, 1996.

Silverman R. The organic chemistry of drug design and drug action. Academic Press. Sand Diego. 1992.

Schlegel H.G. Allgemeine Mikrobiologie. Thieme Verlag. Stuttgart. 1985