Aspects of human bioenergetics as studied in vivo by magnetic resonance spectroscopy

被引:15
作者
Barbiroli, B [1 ]
Iotti, S [1 ]
Lodi, R [1 ]
机构
[1] Dipartimento Med Clin & Biotecnol Applicata D Cam, Biochim Clin, I-40138 Bologna, Italy
关键词
in vivo MR spectroscopy; CoQ; brain bioenergetics; transport of inorganic phosphate; cytosolic free magnesium;
D O I
10.1016/S0300-9084(00)88879-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We outline the relevant capabilities of in vivo phosphorus MR spectroscopy by discussing some aspects of normal human biochemistry as studied by this technique. The transport of inorganic phosphate from cytosol into mitochondria in the human skeletal muscle was studied by exploiting a new experimental protocol. We found that Pi was transported into mitochondria in the absence of ATP biosynthesis and in the presence of a pH gradient. The control of CoQ on the efficiency of oxidative phosphorylation in the skeletal muscle and brain was studied by administering CoQ to patients with mitochondrial cytopathies due to known enzyme defects. Before CoQ we had detected a relevant reduction of mitochondrial functionality in the skeletal muscle as shown by the reduced rate of phosphocreatine recovery from exercise, and in the occipital lobes by reduced [phosphocreatine] and a high [ADP] and [Pi]. After CoQ all brain variables were remarkably improved. Treatment with CoQ also improved the rate of muscle phosphocreatine recovery from exercise. Our in vivo findings support the hypothesis that the concentration of CoQ rather than the rate of its lateral diffusion in the mitochondrial membrane controls the efficiency of oxidative phosphorylation. Other experiments were undertaken to clarify the functional relationship between cytosolic free [Mg2+] and cell bioenergetics in the intact human brain. In the same group of patients with mitochondrial cytopathies we found decreased Delta G of ATP hydrolysis and low cytosolic free [Mg2+]. Treatment with CoQ resulted in improved brain bioenergetics and increased free [Mg2+]. These findings strongly indicate that decreased free magnesium was secondary to defective mitochondrial respiration, and support the hypothesis that cytosolic free [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part any changes in rapidly available free energy. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris.
引用
收藏
页码:847 / 853
页数:7
相关论文
共 46 条
[1]   P-31-NMR SPECTROSCOPY OF SKELETAL-MUSCLE IN BECKER DYSTROPHY AND DMD BMD CARRIERS - ALTERED RATE OF PHOSPHATE-TRANSPORT [J].
BARBIROLI, B ;
FUNICELLO, R ;
IOTTI, S ;
MONTAGNA, P ;
FERLINI, A ;
ZANIOL, P .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1992, 109 (02) :188-195
[2]   DEFECTIVE BRAIN ENERGY-METABOLISM SHOWN BY INVIVO P-31 MR SPECTROSCOPY IN 28 PATIENTS WITH MITOCHONDRIAL CYTOPATHIES [J].
BARBIROLI, B ;
MONTAGNA, P ;
MARTINELLI, P ;
LODI, R ;
IOTTI, S ;
CORTELLI, P ;
FUNICELLO, R ;
ZANIOL, P .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1993, 13 (03) :469-474
[3]   In vivo assessment of human skeletal muscle mitochondria respiration in health and disease [J].
Barbiroli, B ;
Iotti, S ;
Lodi, R .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1997, 174 (1-2) :11-15
[4]  
Barbiroli B, 1997, CELL MOL BIOL, V43, P741
[5]   FURTHER IMPAIRMENT OF MUSCLE PHOSPHATE KINETICS BY LENGTHENING EXERCISE IN DMD BMD CARRIERS - AN IN-VIVO P-31-NMR SPECTROSCOPY STUDY [J].
BARBIROLI, B ;
MCCULLY, KK ;
IOTTI, S ;
LODI, R ;
ZANIOL, P ;
CHANCE, B .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1993, 119 (01) :65-73
[6]   DEFECTIVE BRAIN AND MUSCLE ENERGY-METABOLISM SHOWN BY IN-VIVO P-31 MAGNETIC-RESONANCE SPECTROSCOPY IN NONAFFECTED CARRIERS OF 11778-MTDNA MUTATION [J].
BARBIROLI, B ;
MONTAGNA, P ;
CORTELLI, P ;
IOTTI, S ;
LODI, R ;
BARBONI, P ;
MONARI, L ;
LUGARESI, E ;
FRASSINETI, C ;
ZANIOL, P .
NEUROLOGY, 1995, 45 (07) :1364-1369
[7]   ABNORMAL BRAIN AND MUSCLE ENERGY-METABOLISM SHOWN BY P-31 MAGNETIC-RESONANCE SPECTROSCOPY IN PATIENTS AFFECTED BY MIGRAINE WITH AURA [J].
BARBIROLI, B ;
MONTAGNA, P ;
CORTELLI, P ;
FUNICELLO, R ;
IOTTI, S ;
MONARI, L ;
PIERANGELI, G ;
ZANIOL, P ;
LUGARESI, E .
NEUROLOGY, 1992, 42 (06) :1209-1214
[8]  
BARBIROLI B, 1991, EUROPSIN Q, V27, P36
[9]   HETEROGENEITY OF METABOLIC RESPONSE TO MUSCULAR EXERCISE IN HUMANS - NEW CRITERIA OF INVARIANCE DEFINED BY INVIVO P-31 NMR-SPECTROSCOPY [J].
BENDAHAN, D ;
CONFORTGOUNY, S ;
KOZAKREISS, G ;
COZZONE, PJ .
FEBS LETTERS, 1990, 272 (1-2) :155-158
[10]  
Bendahan D., 1993, MAGMA, V1, P91, DOI 10.1007/BF01760406