A.C. Page

Coenzyme Q. XVII. Isolation of coenzyme Q10 from bacterial fermentation

Abstract Crystalline coenzyme Q10 has been newly isolated from a fermentation using Pseudomonas denitrificans. Previously, the presence of Q9 in Pseudomonas fluorescens, and Q10 in Neurospora crassa and in Chromatium was reported by others, but without evidence based on characterization of isolated crystalline material. We found Q9 in five other species of Pseudomonas, Q8 and Q9 in Pseudomonas fluorescens, and evidence for the presence of some form of Q in 32 cultures, representing 20 species out of 107 cultures which were examined. Coenzyme Q10 can now be produced by a suitable fermentation, rather than by isolation from mammalian tissue.

On the presence and significance of coenzyme Q in microsomes

Mitochondrial and microsomal fractions were prepared from rat liver and particularly from porcine adrenal glands. However, microsomal fractions which are completely free from mitochondrial fragments are very difficult to obtain. Since the succinoxidase enzyme system occurs only in mitochondria, it was possible to determine the percentage of mitochondrial contamination in the microsomal preparations. Such data are necessary in order to estimate the coenzyme Q content of microsomes. Coenzyme Q10 was found in microsomes from porcine adrenal glands, and both Q9 and Q10 were found in the microsomes of rat liver. It appears, therefore, that the coenzyme is implicated in enzyme systems of microsomes as well as those of mitochondria. Further research on adrenal mitochondrial and microsomal enzymic reactions in which coenzyme Q participates may be particularly merited.

Coenzyme Q. XXIV. On the significance of coenzyme Q 10 in human tissues

Abstract Several organs and tissues of three humans have been examined for coenzyme Q content. The liver, heart, spleen, kidney, pancreas, and adrenals contain relatively high concentrations of coenzyme Q 10, indicating that studies of the functional relationship of coenzyme Q to diseases involving any of these organs might be important. The thyroid and brain contain quite low levels of Q. The total body content of coenzyme Q 10 appears to be in the range of 0.5–1.5 g., and the intestinal flora may contribute only negligible amounts of Q 10 to body stores. Coenzyme Q 10 would seem to have an important role in human health and disease, because of (a) its presence in essential organs, (b) its direct link to known vitamin derived coenzymes, (c) its coenzymic functions, and (d) an apparent role in oxidative phosphorylation.

COENZYME Q. LI. NEW DATA ON THE DISTRIBUTION OF COENZYME Q IN NATURE.

The heart of the rhesus monkey was found to contain coenzyme Q 10 . This experimental primate may serve as a model for studies of CoQ 10 as it may relate to human disease. Frog nerve tissue was also found to contain CoQ 10 . Such tissue may be a useful system for researches on CoQ in nerve physiology. Only CoQ 10 was identified in human and rodent tumors grown in mice. The tumor strains were HAd-1, HS-1, and S-180. Cells of Ochromonas malhamensis contain CoQ 10 . It is of interest that both man and this Ochromonas sp. specifically use both CoQ 10 and vitamin B 12 . Contrary to an earlier report that a given Polyporous did not contain a CoQ, it has now been found that Polyporous schweinitzii contains both CoQ 9 and CoQ 10 . The “J strain” of a PPLO ( Mycoplasma gallisepticum ) is of current interest both in respect to its nutrition and its infectious characteristics; this PPLO strain did not contain either a member of either the CoQ or vitamin K groups.

Coenzyme Q. XXXII. Coenzyme Q and the maintenance of sperm cells in Vitro

Compounds of the coenzyme Q and vitamins E and K groups, several water-soluble vitamins, and a few antioxidants were tested for activity for maintenance of motility of sperm. At least 20% of the cells remained motile for 5–7 days in the presence of 1 μg./ml. of the 6-chromanol of coenzyme Q 1 , coenzyme Q 2 and its 6-chromanol and 6-chromenol forms, the 6-chromanol and 6-chromenol of hexahydrocoenzyme Q 4 , and diphenyl- p -phenylenediamine. At concentrations of 10 or 30 μg./ml. of the 6-chromanol of coenzyme Q 1 , the 6-chromanol and 6-chromenol of hexahydrocoenzyme Q 4 , diphenyl- p -phenylenediamine, and “butylated hydroxyanisole,” 53–62% motility was maintained. The same levels of α-tocopherol, α-tocopherylquinone, and 2,3,5-trimethyl-6-phytylbenzoquinone were less effective, and compounds of the vitamin K series were of sporadic and low activity. In the presence of the 6-chromanol of hexahydrocoenzyme Q 4 and α-tocopherol, sperm cells remained motile for more than 2 weeks. The water-soluble vitamins and related compounds were essentially inactive.

Urinary excretion of coenzyme Q10 by patients with diabetes mellitus

Abstract The coenzyme Q 10 content of urines of male and female patients having diabetes mellitus and on occasion atherosclerotic heart disease has been determined. One hundred and twenty-six assays of 24-hr, urine collections from a total of 72 patients have shown that the average daily excretion is ca. 71 μg./24 hr. for male patients and 58 μg./24 hr. for female patients. Although coenzyme Q is sparingly soluble in aqueous media, it has been determined that urine has a capacity to contain at least 3–6 times as much coenzyme Q 10 as is normally found. The highest content of coenzyme Q 10 ever observed in a human urine sample is less than the content which has been determined as possible on the basis of solubility measurement. Thus, urine is not essentially saturated with this sparingly soluble coenzyme. It was found that urine does not contain a bound form of coenzyme Q 10 which can be hydrolyzed to free Q 10 by the saponification technique used in the isolation of Q 10 from tissue.