Red blood cell adenine nucleotides abnormalities in down syndrome

Abstract

The red blood cell adenine nucleotides of 20 Down Syndrome patients and 20 healthy controls were determined by a new high-performance liquid chromatography method. All patients showed increased concentrations of adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP), while adenosine 5'-triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) were within normal ranges. This alternation of the energetic charge could be partly responsible for the impairment of glucose metabolism in these patients.

Red blood cell metabolism in Down syndrome: hints on metabolic derangements in aging

“…T21 RBCs had increased levels of redox markers (eg, glutathione homeostasis), consistent with previous reports on antioxidant enzyme activity. 18,19 Increases in purine oxidation expand on previous reports of deranged adenine nucleoside/energy metabolism in T21 RBCs 17 and may relate to the herein observed signature in carboxylates accumulating in T21 RBCs, potentially explained by compensatory hyperactivation of NADPH-generating isoforms of Krebs cycle enzymes (eg, malate and isocitrate dehydrogenase 1, which are both identified and active in mature erythrocytes) 23 or purine salvage reactions (eg, fumarate, to the extent that these reactions are still active in mature erythrocytes). Increases in RBC levels of pyruvate and lactate as well as acyl-conjugated fatty acids may relate to diabetes and obesity, which are recurring comorbidities in the T21 population, 13 complementing previous lipidomics reports on n-6 fatty acid dysregulation in RBCs from children with T21.…”

“…14 Of note, T21 has been associated with RBC alterations, such as increased cell size (macrocytosis), 15 increased micronutrient levels (eg, copper and zinc), 16 altered adenine 17 and fatty acid/phospholipid levels, 18,19 as well as impaired redox homeostasis, especially with respect to superoxide dismutase (coded by a gene on chromosome 21, 21q22.1), glutathione peroxidase, and lipid peroxidation activity. 18,20 Of note, children with DS presented higher levels of plasma and RBC monounsaturated fatty acids and altered proportions of n-6 choline phosphoacylglycerol species in comparison with disomic siblings.…”

Adenosine A 1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280

“…It has been reported that adenosine receptors are increased in neurons in the degenerating human brain and that administration of an adenosine A 1 receptor agonist induces Aβ production, Tau phosphorylation, and Tau missorting in vitro (31). Down syndrome patients, known to suffer from early-onset AD, have higher levels of adenosine than aged matched controls (32). However, due to the very short half-life of adenosine (<10 s in blood), there have been no studies on adenosine levels in human brain (33).…”

Differences in purine metabolism in patients with Down's syndrome

“…If, as previously suggested, other genes intervening in de novo purine synthesis (for example, adenylosuccinate synthetase) were located on chromosome 21, a metabolic bottle neck could ensue . The increase in adenosine, cAMP and other adenine nucleotides, reported by several authors (Puuka et al (1982); Stocci et al 1985), would have to be compensated for. An example of this attempt to restore homeostasis is the compensatory increase in adenosine deaminase (Bartosz & Kedziora 1983;Ibarra 1990;Puuka et al 1982).…”