Fosfolipaza

Introducere
Hydrolases constitute an enormous proportion of our enzymes, being responsible for the
initiation of most digestive processes and numerous physiological processes. They are defined as
enzymes that use a molecule of water to degrade substrates including all four kinds of biological
molecules; namely, nucleic acids (nucleases), proteins (proteases), lipids or fats (lipases), and
carbohydrates or sugars (glycosidases). They include large families of acyl ester hydrolases,
phosphate, pyrophosphate ester and diester hydrolases, and amide ester hydrolases.
Fosfolipazele sunt o clasa de hidrolaze care catalizeaza hidroliza esterilor acili si esterilor
fosfatati. Hidrolazele constitue o mare parte din enzimele corpului nostru, fiind responsabile pt
initierea proceselor digestive si multe alte procese fiziologice. Fosfolipazele sunt definite in
functie de pozitia pe care o hidroleaza in fosfolipidul respectiv.
Phospholipases constitute a class of hydrolases that catalyze the hydrolysis of acyl esters
(deacylase activity) and phosphate esters (phosphodiesterase or phosphomonoesterase, also
known as phosphohydrolase or phosphatase activity or sometimes pyrophosphatase activity) on
phospholipids (diacylglycerophosphate esters and related compounds) (1). Phospholipases are
defined by the position they hydrolize on the phospholipid backbone as shown in Fig. 1. Of
course, many enzymes are named based on the initial assay used to discover or define their
activity and then are later discovered to exhibit additional activities, and often their predominant
physiological activity is quite different than their name implies. Also, there are certainly many
enzymes not named as phospholipases that exhibit phospholipase activity, sometimes as a side or
minor activity when presented with the appropriate phospholipid substrate.

Tipuri
A

 Descoperire
 Structura
 Rol
 Implicatii clinice/boli

 Are activitate asemanatoare celor doua fosfolipaze PLA1 si PLA2. Deci, ea va hidroliza pozitiile 1
si 2 dintr-un fosfolipid.
 In general, it acts on lysolecithin (which is formed by the action of PLA2 on lecithin).

D
  Principalul substrata supra caruia actioneaza este fosfaditilcolina, hidrolizand-o in acid fosfatidic,
care este transductor intracelular si colina solubila, care va difuza in citosol.
 Are mai multe izoforme, printre care principalele forme sunt PLD1 si PLD2.
 PLD1 este localizata in interiorul celulelor, in aparatul Golgi, lizozomi si granule secretoare.
Activitatea sa este mica si pentru ca ea sa transduca semnalul extracellular, trebuie mai intai
activata de protein precum protein kinaza C. S-a constatat ca dezinhibarea ei de catre alfa-
sinucleina poate contribui la aparitia bolii Parkinson’s.
 PLD2 se afla in membrana celulara si are activitate catalitica mare. Poate fi doar putin activate
de moleculele care activeaza PLD1. S-a observat o activitate ridicata de PLD2 in cancerul de san

Noutati stiintifice
Nature 2014

http://www.nature.com/nature/journal/v505/n7484/abs/nature12825.html

Genome-wide association studies (GWAS) have identified several risk variants for late-onset
Alzheimer's disease (LOAD)1, 2. These common variants have replicable but small effects on
LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants,
not detected by GWAS, are predicted to include functional variants with larger effects on risk. To
identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-
exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate
variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase
D3; Val232Met) segregated with disease status in two independent families and doubled risk for
Alzheimer’s disease in seven independent case–control series with a total of more than 11,000
cases and controls of European descent. Gene-based burden analyses in 4,387 cases and
controls of European descent and 302 African American cases and controls, with complete
sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s
disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to
Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at
significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains.
Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor
protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-
β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and
Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants
have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study
provides an example of how densely affected families may help to identify rare variants with
large effects on risk for disease or other complex traits.

Immunity 2013

http://www.cell.com/immunity/abstract/S1074-7613(13)00463-
9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS10747613130
04639%3Fshowall%3Dtrue&cc=y=
Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also
represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of
venoms from multiple species and is the major allergen in bee venom. Here we examined how bee
venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We
found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate
lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of
interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future
challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect
the activity of a conserved component of venoms and induce a protective immune response against a
venom toxin.