Lipocortin III, ANXA3 tuottaa (hydrolysoi esiin) Inositoli-1-fosfaattimuotoa Ins-2-fosfaatista.

Reaktion merkitys:  Katabolinen  inositolipolyfosfaattien purkaminen fosfaateista  takaisin   siihen inositolimuotoon,  muotoon, josta  voi jälleen alkaa  fosfolipidien synteesi  ( kuten myoinositolin fosfatidihapon ja  CTP-energian avulla   de novo) solussa kohti  PI, PIP, PIP2 muotoja).

 https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/annexin

Inositol Phosphate Metabolism

Theodora S. Ross, in Cellular and Molecular Mechanisms of Inflammation: Signal Transduction in Inflammatory Cells, Part A, 1992

Cyclic Hydrolase

The primary sequence of the cyclic hydrolase is identical to that of lipocortin III, a member of a large family of homologous calcium- and phospholipid-binding proteins without defined biological functions (88). Some of these proteins have been shown to be phosphorylated in response to growth factors. The purified enzyme (33 kDa) is inhibited by inositol 2-phosphate [Ins(2)P], Zn²⁺, and glycerophosphoinositol (GroPIns) and stimulated by acidic phospholipids (87, 89). The pattern of interaction with particular phospholipids is the same as that previously observed for lipocortins (88, 90). The mechanism of inhibition by GroPIns is due to its ability to act as a substrate for this enzyme (89). The regulatory significance of this reaction is unclear, as the level of GroPIns-hydrolyzing activity measured in cellular extracts does not inversely correlate with the cellular levels of GroPIns (T. S. Ross and P. W. Majerus, unpublished observations). The presence of significant amounts of Ins(2)P and GroPIns in cells has been well documented (89, 91) and suggests that they may function as regulators of cellular cIns(1:2)P levels.

Measurement of the cyclic hydrolase activity in cellular extracts has unveiled a very interesting pattern. Cells with relatively low to nondetectable activity were either completely transformed or partially transformed (92). When levels of cyclic inositol phosphates were measured in these cells, it was found that cIns(1:2)P increased in proportion to the decreased cyclic hydrolase activity. The enzyme activity is also increased within one cell type when it is in a confluent state as compared to a logarithmically growing state. Overexpression of cyclic hydrolase in cells decreases the cIns(1:2)P levels as well as the final saturation density. In addition, high endogenous expression of cyclic hydrolase in cells tends to correlate with the differentiated state (e.g., high levels in platelets, brain, and neutrophils and low levels in several immortalized tissue culture cell lines of fibroblasts and T cells). The finding that this correlation exists both in nature and during heterologous expression of the enzyme makes the discovery of a cellular function for cIns(1:2)P likely to be successful. Further studies of the regulation of the cyclic hydrolase activity and cIns(1:2)P cellular levels will yield valuable information as to how to continue the quest for the function(s) of the cyclic bond.

 

 https://www.jlr.org/article/S0022-2275(20)34570-3/fulltext

 https://www.nature.com/articles/ncomms9505

 Jälkimmäisessä artikkelsisa näkyy se Ins-1 fosfaattimuoto, oka rikastuu  PIP muotoon eli muuttuu samalla  vesiliukoisten poly ja monofosfaattein  puolelta rasvaliukoisiin, fosfolipidien puolelle, jolloin siitä tulee  annexiinijärjestelmälle molekyyli, johon  jokin ANX  voi sitoutua. Ainakin ANXA2  tumankalvon  modifioinneissa  solunjaossa  sytokineesin alussa.  PI(4,5)P2 muoto on tuma-alueelle  tunnusomainen PL-muoto.  ( salvage tie, ei:  de novo tie)