Metabolic Mechanisms Underlying Low Circulating Lactate and Pyruvate in Subjects With Alzheimer’s Disease
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 13, Issue 4
Abstract
Subjects with Alzheimer’s disease (AD) may have low levels of circulating lactate and pyruvate but normal plasma ketone bodies (KBs, β-hydroxybutyrate and acetoacetate). In this paper, we point out the underlying mechanisms for the above findings. Low lactate and pyruvate may be accounted for by abnormalities in glycolytic and aerobic pathways, such as reduced glycogen store and/or decreased levels of glucose transport, decreased phosphofructokinase activity, and increases in oxidatively modified glycolytic enzymes. The fact that patients had normal levels of KBs suggests that they were not starving and that their dietary intakes were normal. There are potentially two negative practical consequences of these metabolic abnormalities: reduced residual physical performance and lower provision of energy substrates to several organs including the heart.In a recent investigation by our group, subjects with Alzheimer’s disease (AD) exhibited low plasma lactate and pyruvate concentrations, indicating altered skeletal muscle metabolic energy-generating pathways. This was particularly evident in subjects with a longer diagnosis time (> 5 years). However, the plasma concentrations of ketone bodies (KBs, β-hydroxybutyrate and acetoacetate) were normal [1]. In the present article we point out the metabolic mechanisms underlying both the deficit in circulating lactate and pyruvate, and normal KB concentrations. This could potentially be important for clinical practice in the non-pharmacological treatment of the disease.Abnormalities in glucose breakdown both through the glycolytic and aerobic pathways may account for the changes in plasma lactate and pyruvate. With respect to glycolysis, several steps might be interrupted in the muscles of AD subjects. For example, a reduction in myocyte glucose availability may occur following reduced glycogen store, as a consequence of the activation of the enzyme glycogen synthase kinase 3 β [2] in AD patients. This enzyme inhibits the enzyme glycogen synthase which normally catalyses the synthesis of glycogen. Moreover, other potential glycolytic defects may be decreased levels of glucose transport [3], decreased phosphofructokinase activity [4] (which catalyses the irreversible phosphorylation of fructose-6-phosphate to fructose-1,6 bisphosphate), and increases in oxidatively modified glycolytic enzymes including enolase [5] (which catalyses the conversion of 2-phosphoglycerate to phosphoenolpyruvate). These enzyme defects have been described in neurons. However, in the light of the results of our previous study [1], we postulate that they might also be present in the skeletal muscle of the AD patients in our study.
Authors and Affiliations
Manuela Verri, Roberto Aquilani, Daniela Buonocore, Maurizia Dossena
Keywords
Related Articles
- EP ID EP585697
- DOI 10.26717/BJSTR.2019.13.002449
- Views 128
- Downloads 0
Roles of the Nuclear Receptors PXR1 and PXR2 in the Regulation of Cytochrome P450 3A11 Expression in Mouse Organs and Primary-Cultured Hepatocytes
Pregnane X receptor (PXR) is a nuclear receptor that exists in forms such as PXR1 and PXR2. Activated PXR1 heterodimerizes with retinoid X receptor to increase the transcription of cytochrome P450 3A (CYP3A), a drug-meta...
Lower Extremity Position Test: A Simple Quantitative Proprioception Assessment
Objective: To develop a quantitative, easy to use and inexpensive tool, for assessing proprioception of the lower extremity of older population, to evaluate its test-retest reliability in young and older adult population...
Brain Tumor and Peritumoral Fibers Reconstruction and Visualization With 3D Slicer
Objective: To explore a three dimensional (3D) visualization method for brain tumor and peritumoral fibers with 3D Slicer. Methods: 3D Slicer (version 4.8.1) was download from website (www.slicer.org) and installed. DTI...
An Occult Case of Worsening Dyspnoea in Adult Affected by Anatomic Abnormalities of Oral Cavity: A Case Report
Aspiration of foreign bodies (FBs) occurs frequently in children and most of all occurs in children of about three years old [1]. However, FB aspiration can occur in adults and elderly people [2] but the real incidence i...
Why Managing Your Practice Costs you Time and Money
Everything is Broken The way we traditionally organize de-ntal practices is completely broken. Gallup says only 32% of staff are fully engaged; nearly 70% are phoning it in. A Harris poll shows that 51% of everyone in yo...