Overview of PAF-Degrading Enzymes

Karasawa, Ken; Inoue, Kazuhide

doi:10.1016/bs.enz.2015.09.006

Cited by 23 publications

(16 citation statements)

References 94 publications

(107 reference statements)

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“…Subsequent research revealed that the PAF-AH family includes intracellular forms called PAF-AH I and PAF-AH II, as well as an extracellular third isoform [ 108 ]. PAF-AH, an extracellular isoform in plasma, is a member of the PLA 2 superfamily of enzymes that is also known as lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), since it circulates in blood in association with plasma lipoprotein particles such as LDL and HDL, or the PLA 2 group 7 (PLA 2 G7) [ 107 , 108 , 109 , 110 ]. Intracellular PAF-AH type I exists in the cytoplasm of many (probably all) types of mammalian cells and tissues [ 111 ].…”

Section: The Role Of Paf In Chronic Diseases and The Beneficial Efmentioning

confidence: 99%

“…Interestingly, the intracellular PAF-AH Type II that has no homology with PAF-AH I, but shares sequence similarity to plasma PAF-AH, was reported to act as a cellular Phospholipase A 2 that hydrolyses oxidatively modulated or truncated phospholipids (with short length or oxidatively modified sn -2 acyl chains). It is thus suggested that PAF-AH (II) functions as an antioxidant phospholipase that plays a protective role also against oxidative stress [ 108 , 112 ].…”

Section: The Role Of Paf In Chronic Diseases and The Beneficial Efmentioning

confidence: 99%

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Inflammation, not Cholesterol, Is a Cause of Chronic Disease

2018

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Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices. The relevant studies and data supporting these views are discussed in this review.

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Section: The Role Of Paf In Chronic Diseases and The Beneficial Efmentioning

confidence: 99%

Section: The Role Of Paf In Chronic Diseases and The Beneficial Efmentioning

confidence: 99%

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

2018

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“…PAF is degraded (deacetylated) by PAF acetylhydrolase (PAF-AH) ( Figure 6 , degradation) [ 74 , 75 , 76 ] to yield lysoPAF, which is further acylated by CoA-independent transacylation to regenerate the PAF precursor 1- O -alkyl-2-arachidonoyl-GPC ( Figure 6 , reacylation).…”

Section: Involvement Of the Coa-independent Transacylation System mentioning

confidence: 99%

“…PAF-AHs are PLA2s that hydrolyze PAF and oxidized phospholipids ( Figure 6 and Figure 8 ) [ 74 , 75 , 76 , 80 , 104 ]. PAF-AH I (PLA2G8) is an intracellular PAF-AH.…”

Section: Intracellular Pla2mentioning

confidence: 99%

“…The catalytic subunits PLA2G8A and PLA2G8B (also termed α1 and α2 subunits) form homo- and heterodimers. PAF-AH II (PLA2G7B) is another type of intracellular PAF-AH belonging to the plasma PAF-AH (PLA2G7A) family [ 74 , 75 , 76 , 80 , 105 , 106 ]. These enzymes hydrolyze not only PAF but also oxidized phospholipids—i.e., those that are oxidatively modified to contain short- or medium-chain fatty acids.…”

Section: Intracellular Pla2mentioning

confidence: 99%

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Coenzyme-A-Independent Transacylation System; Possible Involvement of Phospholipase A2 in Transacylation

Yamashita

Hayashi

Matsumoto

et al. 2017

Biology

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The coenzyme A (CoA)-independent transacylation system catalyzes fatty acid transfer from phospholipids to lysophospholipids in the absence of cofactors such as CoA. It prefers to use C20 and C22 polyunsaturated fatty acids such as arachidonic acid, which are esterified in the glycerophospholipid at the sn-2 position. This system can also acylate alkyl ether-linked lysophospholipids, is involved in the enrichment of arachidonic acid in alkyl ether-linked glycerophospholipids, and is critical for the metabolism of eicosanoids and platelet-activating factor. Despite their importance, the enzymes responsible for these reactions have yet to be identified. In this review, we describe the features of the Ca2+-independent, membrane-bound CoA-independent transacylation system and its selectivity for arachidonic acid. We also speculate on the involvement of phospholipase A2 in the CoA-independent transacylation reaction.

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Switching the substrate specificity of lysoplasmalogen‐specific phospholipase D

2021

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Lysoplasmalogen-specific phospholipase D (LyPls-PLD) catalyzes reactions in a manner similar to those catalyzed by glycerophosphodiester phosphodiesterase (GDPD) and other well-known PLDs. Although these enzymes hydrolyze the glycerophosphodiester bond, their substrate specificities are completely different. Previously, we reported that LyPls-PLD from Thermocrispum sp. RD004668 shows only 53% activity with 1-hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (LysoPAF) relative to the 100% activity it shows with choline lysoplasmalogen (LyPlsCho). Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity can be used to evaluate for cardiovascular disease. Hence, development of a point-of-care testing kit requires a LysoPAF-specific PLD (LysoPAF-PLD) to measure Lp-PLA 2 activity. Rational site-directed mutagenesis and kinetic analysis were applied to generate LysoPAF-PLD from LyPls-PLD and to clarify the mechanisms underlying the substrate-recognition ability of LyPls-PLD. Our results suggest that LyPls-PLD variants A47, M71, N173, F211, and W282 are possibly involved in substrate recognition and that F211L may substantially alter substrate preference. Moreover, the specific activity ratio LysoPAF/LyPlsCho corresponding to F211L was up to 25-fold higher than that corresponding to the wild-type enzyme. Thus, we succeeded in switching from LyPlsCho-to LysoPAF-PLD. These results suggest that the F211L variant may be utilized to measure Lp-PLA 2 activity. Kinetic analyses demonstrated that product release was the rate-limiting step of the reaction, with flexibility of the sn-1 ether-linked vinyl/alkyl chain of the substrate being essential for substrate binding and product release. Our findings may lead to a better understanding of the differences between homologous enzymes (such as PLD, sphingomyelinase D, and GDPD of the phosphatidylinositol-phosphodiesterase superfamily) in relation to substrate recognition.Enzyme EC 3.1.4.2 (currently assigned).

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Overview of PAF-Degrading Enzymes

Cited by 23 publications

References 94 publications

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

Coenzyme-A-Independent Transacylation System; Possible Involvement of Phospholipase A2 in Transacylation

Switching the substrate specificity of lysoplasmalogen‐specific phospholipase D

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