(D)-(+)-Neopterin

An Fe2+-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8-dihydro-D-neopterin 2',3'-cyclic phosphate in methanopterin biosynthesis.[Pubmed:19746965]

Biochemistry. 2009 Oct 13;48(40):9384-92.

7,8-Dihydro-D-neopterin 2',3'-cyclic phosphate (H(2)N-cP) is the first intermediate in biosynthesis of the pterin portion of tetrahydromethanopterin (H(4)MPT), a C(1) carrier coenzyme first identified in the methanogenic archaea. This intermediate is produced from GTP by MptA (MJ0775 gene product), a new class of GTP cyclohydrolase I [Grochowski, L. L., Xu, H., Leung, K., and White, R. H. (2007) Biochemistry 46, 6658-6667]. Here we report the identification of a cyclic phosphodiesterase that hydrolyzes the cyclic phosphate of H(2)N-cP and converts it to a mixture of 7,8-dihydro-D-neopterin 2'-monophosphate and 7,8-dihydro-d-neopterin 3'-monophosphate. The enzyme from Methanocaldococcus jannachii is designated MptB (MJ0837 gene product) to indicate that it catalyzes the second step of the biosynthesis of methanopterin. MptB is a member of the HD domain superfamily of enzymes, which require divalent metals for activity. Direct metal analysis of the recombinant enzyme demonstrated that MptB contained 1.0 mol of zinc and 0.8 mol of iron per protomer. MptB requires Fe(2+) for activity, the same as observed for MptA. Thus the first two enzymes involved in H(4)MPT biosynthesis in the archaea are Fe(2+) dependent.

Urinary N-acetyl-beta-D-glucosaminidase and neopterin aid in the diagnosis of rejection and acute tubular necrosis in initially nonfunctioning kidney grafts.[Pubmed:10720893]

Nephron. 2000 Mar;84(3):228-35.

AIM: The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. METHODS: Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN, 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was applied to compute diagnostic performance and an optimal discriminating threshold. RESULTS: Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 +/- 1.0 U/mmol urinary creatinine; neopterin 270 +/- 126 nmol/mmol urinary creatinine; mean +/- SD) as compared with the ATN group (NAG 12 +/- 10 U/mmol, p < 0.001 vs. control group; neopterin 303 +/- 195 nmol/mmol, n.s.) and the rejection group (NAG 7 +/- 8 U/mmol, p < 0. 01; neopterin 508 +/- 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimension nmol neopterin/U NAG activity) increased during rejections as compared with ATN (139 +/- 74 vs. 50 +/- 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 +/- 0.07 (p < 0.001). Applying a ROC-estimated optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection episodes were classified correctly. CONCLUSION: The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants.

The value of combined elevation of D-dimer and neopterin as a predictive parameter for early stage acute mesenteric ischemia: An experimental study.[Pubmed:27278523]

Vascular. 2017 Apr;25(2):163-169.

Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.

Neopterin as a marker for immune system activation.[Pubmed:12003349]

Curr Drug Metab. 2002 Apr;3(2):175-87.

Increased amounts of neopterin are produced by human monocytes/macrophages upon stimulation with the cytokine interferon-y. Therefore, measurement of neopterin concentrations in body fluids like serum, cerebrospinal fluid or urine provides information about activation of T helper cell 1 derived cellular immune activation. Increased neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes. But also in neurological and in cardiovascular diseases cellular immune activation indicated by increased neopterin production, is found. Major diagnostic applications of neopterin measurements are, e.g. monitoring of allograft recipients to recognize immunological complications early. Neopterin production provides prognostic information in patients with malignant tumor diseases and in HIV-infected individuals, high levels being associated with poorer survival expectations. Neopterin measurements are also useful to monitor therapy in patients with autoimmune disorders and in individuals with HIV infection. Screening of neopterin concentrations in blood donations allows to detect acute infections in a non-specific way and improves safety of blood transfusions. As high neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like alpha-tocopherol, neopterin can also be regarded as a marker of reactive oxygen species formed by the activated cellular immune system. Therefore, by neopterin measurements not only the extent of cellular immune activation but also the extent of oxidative stress can be estimated.

Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma.[Pubmed:6429267]

J Exp Med. 1984 Jul 1;160(1):310-6.

Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response-associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.