The identification of <i>p</i>-acetamidobenzoate as a folate degradation product in rat urine

Connor, Michael; Pheasant, Anne E.; Blair, J. Anthony

doi:10.1042/bj1780795

Cited by 26 publications

(16 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When ROS wipe out antioxidant systems, so-called oxidative stress is developing. Vitamin cofactors of homocysteine-converting enzymes, and especially the active cofactor forms such as 5,6,7,8-methylenetetrahydrofolate, are rapidly destroyed upon oxidation and cannot be recycled (27). Consequently, during conditions of overwhelming production of oxidizing compounds, it can be assumed that the intake of essential antioxidant vitamins can become insufficient for proper function of enzymes, and hyperhomocysteinemia may develop even when vitamin supply is normal.…”

Section: Discussionmentioning

confidence: 99%

Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

Ploder

Kurz

Spittler

et al. 2010

Mol Med

View full text Add to dashboard Cite

Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B 12 is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4-d 10) and cysteine (P < 0.05, d 7-d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary.

show abstract

Section: Discussionmentioning

confidence: 99%

Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

Ploder

Kurz

Spittler

et al. 2010

Mol Med

View full text Add to dashboard Cite

show abstract

“…Urine samples and column effluents were counted as described in Connor et al (1979). Faeces were freeze-dried and ground to give a homogeneous powder; 100mg samples were used to estimate total radioactivity as described by Barford et al (1978).…”

Section: Determination Of Radioactivitymentioning

confidence: 99%

“…There have been no detailed studies since the introduction of the unambiguous technique of using a mixture of 14C-and 3H-labelled species by ourselves, and the recognition of a breakdown process as a major route of metabolism of folates in the rat (Murphy et al, 1976;Connor et al, 1979).…”

mentioning

confidence: 99%

Folate metabolism in man: the effect of malignant disease

Saleh¹,

Pheasant²,

Blair³

et al. 1982

Br J Cancer

Self Cite

View full text Add to dashboard Cite

The metabolism of [2-14C]+[3', 5', 7, 9-3H] folic acid and [214C]+[3', 5', 7, 9-3H] 10-formylfolate was studied in hospital inpatients. Metabolites detected in the urine after folic acid feeding included the unchanged compound, other folates and a number of breakdown products, such as p-acetamidobenzoyl-L-glutamate and p-acetamidobenzoate. This confirms the existence of a folate catabolic pathway in man. Patients with malignant disease excreted less of the dose in urine, incorporated more into the reduced folate pool, and showed decreased catabolism of folate, when compared to controls. 10-Formylfolate was excreted largely unchanged, and appears not to be reduced by man. Also 10-formylfolate interfered with the reduction of folic acid given simultaneously.

show abstract

“…However, some 6-5 14-1 14-9 4-2 3-8 24-4 32-9 11-7 11-3 15-9 19-7 0 4 4-1 differences were seen in the proportion of the radioactivity excreted as the different folates. The 3H-labelled scission products were separated by Sephadex G15 into 2 fractions, identified by paper chromatography (Connor et al, 1979) as p-acetamidobenzoylglutamate and p-acetamidobenzoate. Less of the dose was catabolized to scission products by the tumour-bearing animals, despite the retention of more radioactivity in the tissues.…”

mentioning

confidence: 99%

“…Faeces and tissues were freeze-dried, and 100mg samples used to determine total radioactivity as described in Barford et al (1978). Sephadex G15 gel filtration, DEAEcellulose chromatography (Barford, et al, 1977) and paper chromatography (Connor et al, 1979) were performed as described previously.…”

mentioning

confidence: 99%