An update on serine deficiency disorders.

Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported most frequently. The other two disorders in L-serine biosynthesis phosphoserine aminotransferase (PSAT) deficiency and phosphoserine phosphatase (PSP) deficiency have been reported only in a limited number of patients. The biochemical hallmarks of all three disorders are low concentrations of serine in cerebrospinal fluid and plasma. Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of neurometabolic disorders. The use of age-related reference values for serine in CSF and plasma can be of great help in establishing a correct diagnosis of serine deficiency, in particular in newborns and young children.

Age-related increase of kynurenic acid in human cerebrospinal fluid - IgG and beta2-microglobulin changes.

Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases (KAT) I and II. A host of immune mediators influence tryptophan degradation. In the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a group of human subjects aged between 25 and 74 years were determined by using a high performance liquid chromatography method. In CSF and serum KAT I and II activities were investigated by radioenzymatic assay, and the levels of beta(2)-microglobulin, a marker for cellular immune activation, were determined by ELISA. The correlations between neurochemical and biological parameters were evaluated. Two subject groups with significantly different ages, i.e. <50 years and >50 years, p < 0.001, showed statistically significantly different CSF KYNA levels, i.e. 2.84 +/- 0.16 fmol/microl vs. 4.09 +/- 0.14 fmol/microl, p < 0.001, respectively; but this difference was not seen in serum samples. Interestingly, KYNA is synthesised in CSF principally by KAT I and not KAT II, however no relationship was found between enzyme activity and ageing. A positive relationship between CSF KYNA levels and age of subjects indicates a 95% probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA levels significantly correlated with IgG and beta(2)-microglobulin levels (R = 0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was found between other biological parameters in CSF or serum. In summary, a positive relationship between the CSF KYNA level and ageing was found, and the data would suggest age-dependent increase of kynurenine metabolism in the CNS. An enhancement of CSF IgG and beta(2)-microglobulin levels would suggest an activation of the immune system during ageing. Increased KYNA metabolism may be involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic neurotransmission in the ageing CNS.

Amino acids and transaminases activity in ventricular CSF and in brain of normal and Alzheimer patients.

The present study was conducted to determine the concentration of amino acids in the cerebrospinal spinal fluid (CSF) and the activities of two tramsaminases: glutamic oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) in human Alzheimer disease (AD) and normal brain. L-glutamic acid, L-glutamine and L-alanine are the most abundant amino acids in the CSF (50-55% of total amino acids). L-glutamine occurs at much higher levels in Alzheimer CSF compared to the normal CSF (229+/-91.8 nmol/ml in AD versus 107+/-47.2 nmol/ml in normal; P=0.0041). In contrast, L-aspartate occurs at significantly lower concentrations in Alzheimer CSF than normal CSF (46.1+/-25.7 nmol/ml in Alzheimer versus 95.2+/-52.6 nmol/ml in normal; P=0.020). In Alzheimer brain (frontal, parietal and occipital cortices) GOT is present at significantly higher activities than in normal brain cortices (about 1.5 times higher; P<0.01). No significant differences for GPT activity occurred between normal and AD brain. Since CSF receives amino acids from brain tissues, and since GOT catalyzes the conversion of L-aspartate to L-glutamate, the higher concentrations of L-glutamine (which is derived from L-glutamate), and the lower concentrations of L-aspartate found in Alzheimer CSF could be considered as a consequence of the higher activity of GOT that occurs in Alzheimer brain.

[Morphological and biochemical features of cerebral beta-amyloidosis in long-livers]. / Morfobiokhimicheskie osobennosti beta-amiloidozov u dolgozhitelei.

This is the first assessment of the pathogenetic values of some environmental factors in the occurrence and progression of cerebral beta-amyloidosis (Alzheimer's disease, senile dementia) in long-livers of different climatic areas of the Republic of North Ossetia-Alania. New isoenzyme serum assays for determining creatine kinase BB-isoenzyme and the transaminase activity in the spinal fluid are proposed, which may be used as potential markers in the biochemical diagnosis of Alzheimer's disease. They can both provide valuable information on the severity of morphological lesions of cerebral cells in Alzheimer's disease and serve as the basis for the differential diagnosis of different forms of dementia wherein dystrophic changes in CNS cells are absent or slightly pronounced.

Serum and cerebrospinal fluid enzymes in subarachnoid haemorrhage.

Serum levels of creatine kinase (CK) and its isoenzyme CK-MB, lactate dehydrogenase (LDH), hydroxybutyric dehydrogenase (HBDH), glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were studied in 50 patients with subarachnoid haemorrhage. In 18 cases the cerebrospinal fluid (CSF) was also examined for total concentration of CK and CK-MB. The results were correlated with the degree of neurological deterioration, the angiographic spasm and prognosis. Concurrent increase of CK-MB, LDH and HBDH serum levels indicates a poor prognosis, whereas increase of GOT and GPT does not have clinical significance. High CK-MB levels in CSF were associated with the worst clinical evolution. However, increase of serum enzymes coincided in most cases with the appearance of the spasm. Monitoring of CK-MB, LDH and HBDH serum levels can be useful for following the evolution of the spasm and in predicting the outcome for patients with subarachnoid haemorrhage.

[Possible pathways of changes in the activity of a number of enzymes in spinal fluid in stroke]. / O vozmozhnykh putiakh izmeneniia aktivnosti riada fermentov v likvore pri mozgovykh insul'takh.

Examination of 234 cases with cerebral stroke showed that the activity of enzymes in the cerebrospinal fluid (CSF) of these patients increased as compared to the control group. In hemorrhagic strokes their activity was considerably higher than in ischemic ones. In 92 cases the results of examination were compared to sectional findings. The activity of enzymes was affected by numerous factors including the speed of stroke development, its nature, the size of the focus, the distance of the latter from the CSF pathways, and the severity of brain oedema.

[Ultraviolet spectrophotometry of the cerebrospinal fluid in the differential diagnosis of strokes]. / Ul'trafioletovaia spektrofotometriia spinnomozgovoi zhidkosti v differentsial'noi diagnostike insul'tov.

The authors describe the possibility of using the results of ultraviolet spectrophotometry of the cerebrospinal fluid (CSF) for the differential diagnosis of ischemic, hemorrhagic and mixed cerebral strokes. It was found that repeated examinations may be of a definite prognostic value. A correlational analysis showed that the greatest effect on the optical density of the CSF in cases of hemorrhagic strokes is exercised by protein and bilirubin and in cases of ischemic strokes by protein and aspartate aminotransferase (AST).

Lactate dehydrogenase and transaminase activities in the cerebrospinal fluid of protein-energy malnourished children.

The present study is aiming to assess whether there are variations in the activities of the enzymes glutamic-oxalacetic transaminase (GOT) and lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) of children suffering from protein-energy malnutrition (PEM). In this respect, serum and CSF activities of GOT and LDH were assayed in thirteen cases suffering from kwashiorkor and ten normal cases serving as controls. Increased activities of both enzymes in sera and CSF of PEM children compared with normals were observed. The significance of these variations was discussed.

[The activity of aminotransferases in serum and cerebrospinal fluid in neurological diseases (author's transl)]. / Uber die Aktivität der Aminotransferasen in Serum und Liquor cerebrospinalis bei neurologischen Erkrankungen

The activities of the aminotransferases, GOT and GPT, were determined in the serum and cerebrospinal fluid of patients with Parkinson's disease, Huntington's chorea, Wilson's disease, amyotrophic lateral sclerosis (ALS), Friedreich's ataxia, phenylketonuria, and head injuries. 1. In patients with Huntington's chorea the activity of SGOT was lower than in controls (P = 0.02); in Friedreich's ataxia LGPT activity was decreased (P less than 0.001); in patients suffering from ALS SGOT (P = 0.005), SGPT (P less than 0.001) and LGOT (P less than 0.001) activities were increased. 2. Long-term treatment of Parkinson's disease and Wilson's disease with L-dopa resulted in an increase in SGOT, LGOT, and SGPT activity over approximately 2 months, with subsequent normalization of these enzyme activities in spite of continued therapy. Guanidine treatment led to an increase in aminotransferase activities in patients with ALS. Penicillamine caused a decrease in SGOT and SGPT activities in Wilson's disease. These results illustrate the necessity of taking therapeutic measures into account in the interpretation of data on aminotransferase activities.