Tryptophan: a precursor for the endogenous synthesis of norharman in man.

We investigated whether in healthy subjects L-tryptophan may serve as a precursor for the endogenous synthesis of the beta-carboline norharman. For this purpose subjects, smokers as well as non-smokers, received 0 or 1.2 g of an oral dose of tryptophan. Smokers started the experiment 2 h after cessation of smoking. Plasma levels of tryptophan and norharman were measured 100 and 125 min after the start of the experiment. The levels of both compounds were significantly higher in the group receiving tryptophan. Norharman concentrations in the plasma of smokers were significantly higher than in the non-smoking subjects under both experimental conditions. These results add some proof to the hypothesis that in humans tryptophan may serve as a precursor for the synthesis of norharman.

Is delirium after cardiac surgery related to plasma amino acids and physical condition?

The authors studied interrelationships between plasma levels of amino acids, physical condition (as apparent from cortisol, albumin, and thyroid hormone concentrations), and postoperative delirium in 296 patients undergoing elective cardiac surgery. Both plasma tryptophan (Trp) and ratio of Trp to the other large neutral amino acids (oLNAA) were reduced in delirious patients compared with control patients. The lower availability of Trp for the brain in delirious patients may lead to decreased serotonergic function. Besides, the ratio of phenylalanine (Phe) to the oLNAA was increased in delirium, which may result in a higher synthesis of cerebral dopamine and norepinephrine. Delirious patients were also in poorer physical condition than nondelirious patients, having decreased albumin level and increased ratio of inactive reverse triiodothyronine (T3) to active T3. Decreased Trp and increased Phe availability may give rise to an imbalance in cerebral neurotransmitters and thus contribute to delirium.

Incidence of and preoperative predictors for delirium after cardiac surgery.

Incidence of and preoperative predictors for postoperative delirium were studied in 296 patients (age 26-83 years, mean age 63 years) undergoing elective cardiac surgery. Delirium occurred in 40 (13.5%) patients. Predictors included old age, low level of albumin, poor physical condition, use of nifedipine, and a high ratio of the amino acids phenylalanine to the sum of isoleucine, leucine, valine, tyrosine, and tryptophan. These findings suggest that preoperative physical condition and amino acid disturbances may be related to delirium after cardiac surgery in the elderly.

Eicosanoid and amino acid metabolism in transient acute psychoses with psychedelic symptoms.

It has been hypothesized that a disturbance of glutathione (GSH) metabolism might be a common factor in many psychiatric disorders. The aim of the present study was to test this hypothesis in transient acute psychotic patients with distorted perceptions. Since the metabolism of GSH is related to that of thromboxane B2 (TXB2), prostaglandin E (PGE) and some amino acids, we determined these substances in the plasma of 15 patients and 17 normal controls. Plasma concentrations of TXB2 were significantly higher and concentrations of serine and tryptophan were significantly lower in patients than in controls. Large variation was observed in plasma PGE levels in patients, although mean values did not differ significantly from controls. These results are consistent with the hypothesis that the metabolism of GSH is impaired in transient psychotic states.

Norharman and anxiety disorders.

Norharman is a ß-carboline, possibly of endogenous origin, although cigarette smoking and food are sources too. In brain specific binding sites have been demonstrated. In higher doses norharman binds to benzodiazepine receptors and has MAO-B inhibitory activity. From animal experiments it can be concluded that norharman induces sedation and muscle relaxation. A role in psychosis is unclear, a role in the pathogenesis in anxiety is possible, but has to be further substantiated. As current research suggests, norharman may be an important factor in addiction and withdrawal.

Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients.

Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine beta-synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned.

A rare complication of carcinoÏd carcinoma.

In this case report of a patient with carcinoid carcinoma we discuss the normal metabolism of tryptophan, one of the essential amino acids. We also examined the changes of this metabolism due to the metastasis of the carcinoid carcinoma and its psychiatric complications based on a central tryptophan deficiency. A less frequent complication of the changes in the tryptophan metabolism due to carcinoidosis is the disease pellagra. This disease is always accompanied with psychiatric symptoms. It plays an important role in the development of the transmethylation hypothesis of schizophrenia.