Effect of isolated AMP deaminase deficiency on skeletal muscle function

Abstract

Mutation of the AMP deaminase 1 (AMPD1) gene, the predominate AMPD gene expressed in skeletal muscle, is one of the most common inherited defects in the Caucasian population; 2–3% of individuals in this ethnic group are homozygous for defects in the AMPD1 gene. Several studies of human subjects have reported variable results with some studies suggesting this gene defect may cause symptoms of a metabolic myopathy and/or easy fatigability while others indicate individuals with this inherited defect are completely asymptomatic. Because of confounding problems in assessing muscle symptoms and performance in human subjects with different genetic backgrounds and different environmental experiences such as prior exercise conditioning and diet, a strain of inbred mice with selective disruption of the AMPD1 was developed to study the consequences of muscle AMPD deficiency in isolation. Studies reported here demonstrate that these animals are a good metabolic phenocopy of human AMPD1 deficiency but they exhibit no abnormalities in muscle performance in three different exercise protocols.

AMPD1: a novel therapeutic target for reversing insulin resistance

“…To address the question of whether AMPD represents a valid new target for drug development to reverse or ameliorate insulin resistance we have taken the approach of gene disruption to test this hypothesis more definitively. In particular we elected to reduce the level of AMPD enzyme activity in skeletal muscle through disruption of the AMPD1 gene, the predominant AMPD gene expressed in skeletal muscle [ 6 , 7 ]. The results described in this report demonstrate that mice rendered deficient in AMPD1 enzyme activity have a milder state of insulin resistance, improved glucose tolerance, and enhanced insulin clearance when fed a high fat diet when compared to controls with normal skeletal muscle AMPD enzyme activity.…”

McArdle disease causing rhabdomyolysis following vaginal delivery

“…Additionally, this parturient's AMPD1 deficiency—characterised by an inability to break down adenosine monophosphate to inosine monophosphate—may have been contributory. Although it is unlikely that the AMPD1 deficiency alone impaired muscle performance , the combination of two disorders could have increased her susceptibility to rhabdomyolysis.…”

Raumenų adaptaciją prie fizinių krūvių lemiančių „CKM“ ir „AMPD1“ genetinių variantų analizė Lietuvos sportininkų grupėje

“…Mokslininkai teigia, kad AMPD1 T alelio ir TT genotipo dažnis yra daug retesnis sportininkų grupėje nei kontrolės (Fisher et al, 2007;Cieszczyk et al, 2012;Fedotovskaya et al, 2013;Grealy et al, 2015). Tai nenuostabu, kadangi yra žinoma, kad šis polimorfizmas AMPD1 gene sukuria priešlaikinį baigmės kodoną ir lemia nefunkcionalaus sutrumpėjusio baltymo (mioadenilato deaminazės) sintezę žmogaus raumenyse (Rico-Sanz et al, 2003;Dias et al, 2007;Hayes, et al, 2013;Cheng et al, 2014). AMPD1 TT genotipo asmenys turi mioadenilato deaminazės stoką ir dažnai patiria raumenų silpnumą fizinio krūvio metu (Dias et al, 2007;Hayes, et al, 2013).…”

“…AMPD1 TT genotipo asmenys turi mioadenilato deaminazės stoką ir dažnai patiria raumenų silpnumą fizinio krūvio metu (Dias et al, 2007;Hayes, et al, 2013). Taip pat daugelyje literatūros šaltinių aprašomi atvejai, kai mioadenilato deaminazės stoka (TT genotipo asmenų) pasireiškia įvairiomis formomis: be simptomų, metaboline miopatija, sutrikusia raumenų funkcija fizinio krūvio metu (De Ruiter et al, 2002;Rico-Sanz et al, 2003;Fisher et al, 2007;Cheng et al, 2014). Mokslininkai teigia, kad AMPD1 TT genotipo asmenys pasižymi reikšmingai mažesniu anaerobiniu pajėgumu nei CT ir CC genotipo asmenys (Fisher et al, 2007;Ahmetov, Fedotovskaya, 2012;Fedotovskaya et al, 2013).…”