The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

Abstract

Summary: Although paraoxonase is synthesized in many tissues including the heart, colon, kidneys, lungs, small intestines and brain, its major locus of synthesis is the liver. PON1 is in close association with apolipoproteins and protects LDL against oxidation. It was reported that PON1 quantities dropped to 40 times lower than normal in cardiovascular diseases and diseases like diabetes, ulcerative colitis, Crohn's disease, chronic renal failure, SLE, Behcet's disease, cancer, hepatitis B, obesity, metabolic syndrome, Alzheimer's and dementia. It is speculated that the concerning decline in serum PON1 amount results from single nucleotide polymorphism in the coding (Q192R, L55M) and promoter (T-108C) sites of the PON1 gene. Additionally, circulating amounts of PON1 are affected by vitamins, antioxidants, fatty acids, dietary factors, drugs, age and lifestyle. This collection attempts to review and examine the past and present studies of paraoxonase and its relation with the cardiovascular system and some relevant diseases.Keywords: paraoxonase, polymorphism, cardiovascular system diseases Kratak sadr`aj: Iako se paraoksonaza sinteti{e u mnogim tkivima, uklju~uju}i srce, debelo crevo, bubrege, plu}a, tanko crevo i mozak, glavno mesto njene sinteze je jetra. PON1 je blisko povezana sa apolipoproteinima i {titi LDL od oksidacije. Koli~ine PON1 ~ak 40 puta ni`e od normalnog nivoa zabele`ene su u kardiovaskularnim bolestima i oboljenjima kao {to su dijabetes, ulcerozni kolitis, Kronova bolest, hroni~na bubre`na insuficijencija, sistemski eritemski lupus, Beh~etov sindrom, kancer, hepatitis B, gojaznost, metaboli~ki sindrom, Alchajmerova bolest i demencija. Spekuli{e se da pomenuti pad nivoa PON1 u serumu poti~e od polimorfizma pojedina~nih nukleotida na kodnim (Q192R, L55M) i promoterskim (T-108C) podru~jima gena PON1. Pored toga, na koli~inu PON1 u cirkulaciji uti~u vita mini, antioksidansi, masne kiseline, faktori ishra ne, le kovi, godine i na~in `ivota. Ovaj pregled predstavlja poku{aj da se izlo`e i razmotre pro{le i sada{nje studije o paraoksonazi i njenom odnosu sa kardiovaskularnim sistemom i nekim relevantnim bolestima.

The Phenotype Distribution of Paraoxonase-1 in Patients with Multiple Myeloma, Bladder, and Colorectal Cancer

“…However, cigarette smoking, acute phase proteins, pregnancy and diet affect serum PON1 activities (5)(6)(7). Reduced PON1 enzyme activities have been shown in several groups of patients with hypercholesterolemia, diabetes mellitus, and cardiovascular disease, in which the patients are under increased oxidative stress (8,9). PON1, PON2 and PON3 are members of a family of proteins.…”

The impact of chronic untreated hyperglycaemia on the long-term stability of paraoxonase 1 (PON1) and antioxidant status in human sera

“…Since the oxidation of LDL is a key process in the pathophysiology of atherosclerosis and cardiovascular disease, it is not surprising that the enzyme has attracted immense scientific interest in the last two decades. In addition to cardiovascular health, PON1 has been widely investigated in many other areas including, but not limited to, drug metabolism,5 nephrology, neurobiology, cancer biology, autoimmunity and ageing (reviewed in 6). …”