Probable mechanism of catalysis of pineal gland hydroxyindole-O-methyltransferase (HIOMT) from rainbow trout (Salmo gairdneri)

Pineal glands were obtained from two young female black rhinoceri that had died as a result of postcapture trauma during a translocation exercise. Hydroxyindole-O-methyltransferase (HIOMT) from these pineal glands showed a peak activity at pH 8.2, although high activity extended over a fairly wide pH range (7.8-8.4). N-acetylserotonin was the best hydroxyindolic substrate for the enzyme, although other hydroxyindoles were methylated, the relative affinities being similar to values previously reported for bovine HIOMT. Kinetic analyses revealed that black rhinoceros HIOMT was subject to substrate inhibition by both substrates at high concentration; this observation is unlikely to have physiological significance. The catalytic mechanism was found to be ordered Bi-Bi, in which S-adenosylmethionine is the obligatory first substrate to bind to the enzyme, such binding allowing for binding of the hydroxyindolic substrate followed by catalysis, products again leaving the catalytic site in a sequential fashion.

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Some Properties of Pineal Gland Hydroxyindole‐O‐Methyltransferase From Black Rhinoceros (Diceros bicornis)

Morton

Kock

1990

“…'Data from Axelrod and Weissbach [1961]. gData from Morton and Forbes [1989]. hData from Eichler and Moore [1975].…”

Section: Discussionmentioning

confidence: 99%

Hydroxyindole‐O‐methyltransferase activity in ocular and brain structures of rabbit and hen

Nowak

Szymańska

Zawilska³

et al. 1993

Relative activities of hydroxyindole-O-methyltransferase (HIOMT) of some brain and ocular structures of the rabbit and hen were analyzed using different 5-hydroxyindoles, i.e., N-acetylserotonin (NAS), 5-hydroxytryptophol (HTOL), 5-hydroxytryptophan (HTP), 5-hydroxytryptamine (HT), and 5-hydroxy-3-indoleacetic acid (HIAA), as enzyme substrates. Pineal glands of both species, as well as hen retina, are capable of producing, to varying degrees, melatonin, 5-methoxytryptophol, and 5-methoxytryptamine. Hen choroid and iris-ciliary body O-methylated NAS and HTOL, whereas rabbit choroid and, to a much lesser extent, hypothalamus and cerebral cortex all O-methylated only NAS. No measurable HIOMT activity was found in hen brain. NAS was a preferred substrate for HIOMT in the hen tissues, whereas in the rabbit pineal gland NAS and HTOL were equally good substrates for HIOMT. Other tested 5-hydroxyindoles, i.e., HTP, HT, and HIAA, were poor methyl acceptors. Of the tissues examined, the highest HIOMT activity was found in the hen pineal gland, followed by the rabbit pineal gland and hen retina. No significant differences between day and nighttime enzyme activities were observed in the pineal gland and retina of either species. The data suggest that in vertebrates some nervous and ocular tissues possess the potential to produce 5-methoxyindole compounds; however, the HIOMT-catalyzed process shows remarkable substrate-, tissue- and species-dependent variations.

“… a , b , c , d , e , f , g , h , i , j , k . The ASMT activities were measured via methylation efficiency for N‐acetylserotonin to form melatonin or serotonin to form 5‐MT.…”

Section: The Alternate Melatonin Synthetic Pathway In Animals?mentioning

confidence: 99%

On the significance of an alternate pathway of melatonin synthesis via 5‐methoxytryptamine: comparisons across species

Tan

Hardeland

Back

et al. 2016

246

206

Melatonin is a phylogenetically ancient molecule. It is ubiquitously present in almost all organisms from primitive photosynthetic bacteria to humans. Its original primary function is presumable to be that of an antioxidant with other functions of this molecule having been acquired during evolution. The synthetic pathway of melatonin in vertebrates has been extensively studied. It is common knowledge that serotonin is acetylated to form N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT) or arylamine N-acetyltransferase (SNAT or NAT) and N-acetylserotonin is, subsequently, methylated to melatonin by N-acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole-Omethyltransferase, HIOMT). This is referred to as a classic melatonin synthetic pathway. Based on new evidence, we feel that this classic melatonin pathway is not generally the prevailing route of melatonin production. An alternate pathway is known to exist, in which serotonin is first O-methylated to 5-methoxytryptamine (5-MT) and, thereafter, 5-MT is N-acetylated to melatonin. Here, we hypothesize that the alternate melatonin synthetic pathway may be more important in certain organisms and under certain conditions. Evidence strongly supports that this alternate pathway prevails in some plants, bacteria, and, perhaps, yeast and may also occur in animals.