Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

Abstract

Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.

Acidemia Metilmalónica: presentación de un caso y revisión de la literatura científica

“…La AMM neonatal tiene un curso clínico agudo y severo, tras un periodo libre de síntomas, los pacientes se deterioran mostrando pobre succión, vomito, anorexia, distensión abdominal, somnolencia y coma por encefalopatía (2,8).…”

“…Las formas crónicas progresivas reportadas son: anorexia, vómito, falla de medro, cardiomiopatía, osteoporosis, pancreatitis, dermatitis, úlceras corneales, hipotonía, convulsiones, y desórdenes del movimiento (8,10,11). Una complicación neurológica es el síndrome extrapiramidal progresivo por edema y necrosis del globus pallidus, que se asocia a atrofia cortical, retardo en mielinización y neuropatía óptica (8,12,13).…”

Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

“…Brain energy metabolism alterations play an important role in the pathophysiology of many inborn errors of metabolism [80][81][82][83]. In this context, energy metabolism impairment was reported in HPA animal models and patients.…”

Investigation on the Mechanism of Qi-Invigoration from a Perspective of Effects of Sijunzi Decoction on Mitochondrial Energy Metabolism

“…Mitochondrial creatine kinase is an important component of the cellular energy buffering and transport system, connecting oxidative phosphorylation to ATP consumption. The reduced activity of creatine kinase may lead to a decreased cellular ATP/ADP ratio [15].…”

“…Mitochondrial ATP-sensitive K + channel (mitoK ATP ) opening results in decreased mitochondrial ROS production. In addition, under energy deprivation conditions, mitoK ATP opening inhibits mitochondrial ATP hydrolysis by ATP synthase, which helps to keep the cytosolic ATP/ADP ratio and also to limit mitochondrial Ca 2+ uptake, indirectly preventing MPT [15].…”