PMID- 8816948
OWN - NLM
STAT- MEDLINE
DCOM- 19961031
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1276
IP  - 2
DP  - 1996 Sep 12
TI  - Differential effects of creatine depletion on the regulation of enzyme activities 
      and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, 
      and brain.
PG  - 161-70
AB  - Guanidinopropionic acid (GPA), an analogue of creatine (Cr), is known to inhibit 
      Cr uptake by cells. The metabolic effects of chronic Cr depletion on brain, heart 
      and soleus muscle of rats were studied. In GPA hearts and soleus muscle, total 
      specific creatine kinase (CK) activity was decreased by approx. 40% compared to 
      controls, whereas in brain this same activity was elevated by a factor of two. 
      Immunoblot analysis of soleus mitochondria from GPA rats showed an approximate 
      4-fold increase in Mi-CK protein and a concomitant 3-fold increase in adenine 
      nucleotide translocator (ANT) protein, when compared to control. In GPA-fed rats, 
      the specific activities of adenylate kinase (ADK) and succinate dehydrogenase 
      were significantly higher in brain and soleus (2-fold), but heart remained the 
      same. However, hexokinase (HK) decreased by approx. 50% both in heart and soleus, 
      indicating that muscle and brain follow different strategies to compensate the 
      energy deficit caused by creatine depletion. Skinned muscle fibres from 
      Cr-depleted soleus attained approx. only 70% maximum state 3 respiration with 0.1 
      M ADP in the presence of 10 mM Cr compared to 100% in control fibres. This defect 
      in Cr stimulated respiration was also seen in isolated heart mitochondria, but 
      was normal in those from brain. The observed deficit of Cr-stimulated 
      respiration, the significant accumulation of Mib-CK and ANT, concomitant with the 
      formation of Mib-CK rich intra-mitochondrial inclusions shown by electron 
      microscopy, indicate that Mib-CK function and coupling to oxidative 
      phosphorylation (OXPHOS), is impaired in these abnormal mitochondria. In 
      addition, our results show tissue-specific metabolic compensations to Cr 
      depletion.
FAU - O'Gorman, E
AU  - O'Gorman E
AD  - Institute for Cell Biology, Swiss Federal Institute of Technology, Zurich, 
      Switzerland.
FAU - Beutner, G
AU  - Beutner G
FAU - Wallimann, T
AU  - Wallimann T
FAU - Brdiczka, D
AU  - Brdiczka D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Guanidines)
RN  - 0 (Isoenzymes)
RN  - 0 (Propionates)
RN  - 9068-80-8 (Mitochondrial ADP, ATP Translocases)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - MU72812GK0 (Creatine)
RN  - UL1984YRKA (guanidinopropionic acid)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Creatine/*deficiency
MH  - Creatine Kinase/analysis
MH  - Female
MH  - *Gene Expression Regulation, Enzymologic
MH  - Guanidines/pharmacology
MH  - Heart/drug effects
MH  - Isoenzymes/analysis
MH  - Mitochondria/*metabolism
MH  - Mitochondrial ADP, ATP Translocases/analysis
MH  - Muscle, Skeletal/drug effects/metabolism/ultrastructure
MH  - Muscles/drug effects/*metabolism/ultrastructure
MH  - Myocardium/metabolism
MH  - Oxidative Phosphorylation
MH  - Oxygen Consumption
MH  - Propionates/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1996/09/12 00:00
MHDA- 1996/09/12 00:01
CRDT- 1996/09/12 00:00
PHST- 1996/09/12 00:00 [pubmed]
PHST- 1996/09/12 00:01 [medline]
PHST- 1996/09/12 00:00 [entrez]
AID - 0005-2728(96)00074-6 [pii]
AID - 10.1016/0005-2728(96)00074-6 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1996 Sep 12;1276(2):161-70. doi: 
      10.1016/0005-2728(96)00074-6.