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31P-MRS muscolo scheletrico
Respirazione mitocondriale
Glicogenolisi e glicolisi
pH intracellulare (citosolico)
Mg2 libero del citosol
Metabolismo ionico
Trasporto del Pi nel mitocondrio
Efflusso di H dal citosol
DG ATP idrolisi
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Stress metabolico
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Esercizio muscolare
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Recupero dallesercizio
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PCr
Livello a riposo
a
(uniotà arbitrarie MRS)
PCr
b ultimo livello di lavoro
Tempo di recupero (s)
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Glycolytic test
CUFF
ON
REST
RECOVERY
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WORK
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PCr (mM)
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0
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Pi
Pi resting level
b last level of work
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ATP Cr
PCr ADP H
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ATP Cr
PCr ADP H
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270 J/min
minimum pH
418 J/min
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carrier mitocondriale di Pi (rate limiting)
Driving force gradiente di pH (pH 8.0 matrice
pH 6.0 citosol)
La velocità di recupero di PCr e di Pi
sono inversamente proporzionali al valore di pH
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calf muscle 31P MRS in DMD/BMD carriers
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Condizioni per la valutazione della velocità di
recupero di PCr dallesercizio
__________
pH minimo minore di 6,90
Eccesso di substrati
Alto ADP (gt 60 mM)
Alto Pi (gt 25 mM)
Alto O2 (iperemia)
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0
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mtDNA mutation at bp 117788
0
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0
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mitochondrial cytopathies
Chronic Progressive External Ophtalmoplegia
(CPEO) mtDNA deletion/s (Cox deficit), RRF
Lebers Hereditary Optic Neuropathy (LHON)
11778 bp mtDNA mutation (Complex
I) Mitochondrial myopathy (MM) mtDNA deletion/s
(Cox / SDH deficit), RRF Mitochondrial
encephalomyopathies MEM MELAS (3243 mtDNA
mutation (tRNA-leu), RRF, SCR deficit,) MERRF
(Myoclonal epilespsy w. RRF) - 8993 mtDNA
mutation (tRNA-lys), RRF
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CPEO (Cox deficit) control
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PCr
Pi
normal control MELAS patient
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reference values (95 confidence interval)
4.82
2.43
controls
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Control
TC 38s pH 6.58
CPEO (Cox deficit)
PCr recovery (MRS arbitrary units)
TC 58s pH 6.62
Recovery time (s)
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Reference range (95 confidence interval)
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Multiple logistic regression applied to two
independent indicators 1. Pi at rest, 2.
rate of PCr recovery
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PrD (probability of disease)
1 e -(0.538 Ds 4.312 P 23.729)
Ds rate of PCr recovery (sec)
P Pi at rest
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HEADACHE (over 120 patients studied)
(brain occipital lobes)
Failure of mitochondrial energy transductions in
the brain of all patiens with headache is a
favouring background for the triggering of
headache
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skeletal muscle (gastrocnemius)
HEADACHE (over 120 patients studied)
Failure of skeletal muscle energy tranductions
lead us to put forward the hypothesis that
headache is a systemic disease primarely
involving energy metabolism
The rate of PCr recovery after exercise is a
measure of mitochondrial funtionality
dashed area defines the reference interval
A MS B MwA C MwoA D CH
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Glicogenosi muscolari
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McArdle
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Deficit di PFK
No pH variation during work and recovery
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Deficit di PGAM
No pH variation during work and recovery
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Valutazione delleffetto della terapia
trattamento con CoQ pazienti con citopatie
mitocondriali
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Mitochondrial myopathies
Reference range
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Normal
31P MRS
BLOOD ANALYSIS Biochemistry, molecular
genetic MUSCULAR BIOPSY Histochemistry,
biochemistry, molecular genetic
Abnormal
Diagnosis confirmation
31P MRS