However, the increased production of NO by iNOS, primed by inflammatory cytokines, leads to an S-nitrosylation of reactive cysteine in DDAH
, inhibiting ADMA catabolism, thus increasing its levels and lastly inhibiting all three isoforms of NOS .
Hyperglycemia in type 2 diabetic patients impairs an enzyme, DDAH
which is responsible for the degradation of ADMA, thus leading to high concentration of ADMA in blood8.
In humans, DDAH
exists as two isoforms, DDAH1 and DDAH2.
activity in diabetic neuropathy patients should be examined in further clinical studies.
Homocysteine induced accumulation of asymmetric dimethylarginine: role of DDAH
and effect of antioxidants.
Revisando la literatura sobre la relacion de los polimorfismos del gen VEGF, aparte de los trabajos que si hallan asociacion -como los senalados anteriormente, y que incluyen aquellos sobre el polimorfismo del alelo +936, como los Shim (15) y Papazoglou (11)-, en otros mas recientes no se ha encontrado dicha asociacion con los polimorfismos de VEGF +936C/T (18), en el alelo +813C (20), los alelos menores VEGF rs699947, rs1570360, rs2010963 y rs25648 (21), polimorfismos de los genes eNOS, DDAH
y VEGF (22), y con los polimorfismos del gen de VEGF -2578C/A, -634G/C; el 936C/T en estudio, solo fue encontrado asociado con la preeclampsia severa (11).
ADMA is primarily metabolized to citrulline and dimethylamine by the enzyme dimethylaminohydrolase (DDAH
), which has high activity in the liver and kidneys [69-71].
EFFECTS OF TOBACCO SMOKE ON ADMA LIBERATION AND DDAH
EXPRESSION IN EAhy 926 CELLS
ADMA, the endogenous NO inhibitor, also increases in dyslipidemia probably due to inhibition of dimethyl diamino hydrolase (DDAH
) which is the enzyme responsible for ADMA catabolism because of low grade chronic inflammation.
Unchanged ADMA is excreted by the kidneys, but the greatest part of endogenously produced ADMA (about 90%) is excreted in the urine as dimethylamine (DMA) after hydrolysis by the enzyme dimethylarginine dimethylaminohydrolase (DDAH
) , predominantly in kidney and liver.
Wild type (WT) C57BL/6 and dimethylarginine dimethylaminohydrolase transgenic (DDAH-I) mice on the C57BL/6 strain that overexpress DDAH
were originally obtained from The Jackson Laboratory (Bar Harbor, ME) and subsequently bred and maintained in microisolator units in the UNMC specific pathogen-free animal facility.
Dimethylamine dimethylaminohydrolase (DDAH
) converts ADMA to citrulline and dimethylamine.