Acetyl-1-14C-l-carnitine Oxidation, Carnitine Acetyltransferase Activity, and CoA Content in Skeletal Muscle Mitochondria from Normal and Dystrophic Mice (Strain 129)

1972 ◽  
Vol 50 (7) ◽  
pp. 749-754 ◽  
Author(s):  
J. J. Jato-Rodriguez ◽  
C. H. Lin ◽  
A. J. Hudson ◽  
K. P. Strickland
Keyword(s):  
Skeletal Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Carnitine Acetyltransferase ◽  
Dystrophic Muscle ◽  
Mitochondrial Content ◽  
Acid Cycle ◽  
Skeletal Muscle Mitochondria ◽  
Leg Muscle ◽  
Dystrophic Mice

Mitochondria isolated from the hind leg muscle of normal and dystrophic mice (strain 129) were compared in their capacity to oxidize acetyl-1-14C-l-carnitine. Oxidation in the mitochondria from dystrophic animals was reduced by 80%. Carnitine acetyltransferase (EC 2.3.1.7) activity in the mitochondria was determined and showed a 35% reduction in the mitochondria from dystrophic muscle. A larger decrease (55%) was observed in the mitochondrial content of acid-soluble CoA. Although the combined decreases in carnitine acetyltransferase and CoA can largely account for the observed decrease in acetylcarnitine oxidation in the mitochondria isolated from dystrophic muscle, it is conceivable that some defect may still exist in the utilization of acetyl groups in the tricarboxylic acid cycle.

scholarly journals Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression

2000 ◽  
Vol 346 (3) ◽  
pp. 651-657 ◽  
Author(s):  
Mary C. SUGDEN ◽  
Alexandra KRAUS ◽  
Robert A. HARRIS ◽  
Mark J. HOLNESS
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Pyruvate Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Cycle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Anterior Tibialis

Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation. Starvation increased PDK activity in both slow-twitch (soleus) and fast-twitch (anterior tibialis) skeletal muscle and was associated with loss of sensitivity of PDK to inhibition by pyruvate, with a greater effect in anterior tibialis. Starvation significantly increased PDK4 protein expression in both soleus and anterior tibialis, with a greater response in anterior tibialis. Starvation did not effect PDK2 protein expression in soleus, but modestly increased PDK2 expression in anterior tibialis. Refeeding for 4 h partially reversed the effect of 48-h starvation on PDK activity and PDK4 expression in both soleus and anterior tibialis, but the response was more marked in soleus than in anterior tibialis. Pyruvate sensitivity of PDK activity was also partially restored by refeeding, again with the greater response in soleus. It is concluded that targeted regulation of PDK4 isoenzyme expression in skeletal muscle in response to starvation and refeeding underlies the modulation of the regulatory characteristics of PDK in vivo. We propose that switching from a pyruvate-sensitive to a pyruvate-insensitive PDK isoenzyme in starvation (a) maintains a sufficiently high pyruvate concentration to ensure that the glucose → alanine → glucose cycle is not impaired, and (b) may ‘spare’ pyruvate for anaplerotic entry into the tricarboxylic acid cycle to support the entry of acetyl-CoA derived from fatty acid (FA) oxidation into the tricarboxylic acid cycle. We further speculate that FA oxidation by skeletal muscle is both forced and facilitated by upregulation of PDK4, which is perceived as an essential component of the operation of the glucose-FA cycle in starvation.

scholarly journals Activity and androgenic control of enzymes associated with the tricarboxylic acid cycle, lipid oxidation and mitochondrial shuttles in the epididymis and epididymal spermatozoa of the rat

1978 ◽  
Vol 174 (3) ◽  
pp. 741-752 ◽  
Author(s):  
D E Brooks
Keyword(s):  
Lipid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Active Member ◽  
Carnitine Acetyltransferase ◽  
Atp Citrate Lyase ◽  
Acid Cycle ◽  
Citrate Lyase ◽  
Epididymal Spermatozoa ◽  
Glycerol 3 Phosphate Dehydrogenase

1. Enzyme activities (units/g wet wt.) were determined in the caput and cauda epididymidis and in epididymal spermatozoa of the rat. 2. The activity of most enzymes in the cauda was between 50 and 100% of that in the caput, except that ATP citrate lyase was barely detectable in the cauda. 3. Spermatozoa, unlike epididymal tissue, contained sorbitol dehydrogenase but lacked ATP citrate lyase. NADP+-malate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, succinate dehydrogenase, carnitine acetyltransferase and citrate synthase were 5 to 400 times as active in spermatozoa as in epididymal tissue. 4. 2-Oxoglutarate dehydrogenase was the least active member of the tricarboxylic acid cycle in all tissues and most closely matched the measured flux through the cycle. 5. The concentrations of hydroxyacyl-CoA dehydrogenase and carnitine palmitoyltransferase were equivalent to the more active enzymes of the tricarboxylic acid cycle, indicating the capacity for extensive lipid oxidation, and the presence of 3-hydroxybutyrate dehydrogenase suggests that these tissues can also oxidize ketone bodies. 6. Transfer of reducing equivalents from cytoplasm to mitochondrion is unlikely to occur by means of the glycerol phosphate cycle because mitochondrial glycerol 3-phosphate dehydrogenase is relatively inactive in epididymal tissue, whereas the cytoplasmic enzyme has little activity in spermatozoa, but transfer may be accomplished by the malate-aspartate shuttle. 7. Transfer of acetyl units from mitochondrion to cytoplasm could be effected by the pyruvate-malate cycle in the caput of androgen-maintained rats, but not in the other tissues because of the low activity of ATP citrate lyase. Acetyl unit transfer could take place via acetylcarnitine, mediated by carnitine acetyltransferase. 8. Castration resulted in a decrease in the concentration of nearly all enzymes, although subsequent administration of testosterone restored concentrations to values similar to those in animals maintained by endogenous androgen. The extent to which enzyme concentration was changed by an alteration in androgen status was highly variable, but was most marked in the case of pyruvate carboxylase.

Impairment of the Tricarboxylic acid cycle in skeletal muscle of zymosan treated rats

1993 ◽  
Vol 12 ◽  
pp. 20-21
Author(s):  
A.J.M. Wagenmakers ◽  
O.E. Rooyackers ◽  
W.H.M. Saris ◽  
P.B. Soeters
Keyword(s):  
Skeletal Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle

Palmitic acid-1-14C oxidation by skeletal muscle mitochondria of dystrophic mice

1970 ◽  
Vol 48 (5) ◽  
pp. 566-572 ◽  
Author(s):  
C. H. Lin ◽  
A. J. Hudson ◽  
K. P. Strickland
Keyword(s):  
Skeletal Muscle ◽  
Palmitic Acid ◽  
Krebs Cycle ◽  
Supernatant Fraction ◽  
Dystrophic Muscle ◽  
Muscle Mitochondria ◽  
Normal Littermate ◽  
Skeletal Muscle Mitochondria ◽  
Dystrophic Mice ◽  
Muscle Homogenate

Cofactor requirements for the oxidation of palmitate-1-14C by 600 × g supernatant fraction of mouse skeletal muscle homogenate and by skeletal muscle mitochondria are described. Optimal oxidation of palmitate-1-14C by skeletal muscle mitochondria requires the presence of carnitine, ATP, CoA, and a Krebs cycle intermediate (e.g. succinate). Succinate, malate, alpha-ketoglutarate, and oxaloacetate are all equally effective in supporting the oxidation, but isocitrate is less effective. The oxidation of palmitate-1-14C by 600 × g supernatant fraction of muscle homogenate as well as by skeletal muscle mitochondria from dystrophic mice is significantly decreased compared with that of the normal littermate controls. The present results, together with the previous findings, suggest that the decrease in oxidation of palmitate-1-14C by the dystrophic muscle preparations is most likely due to a defect in one or more of the steps of the Krebs cycle.

Lack of genetic polymorphism in human skeletal muscle enzymes of the tricarboxylic acid cycle

1987 ◽  
Vol 77 (2) ◽  
pp. 200-200 ◽  
Author(s):  
Martine Marcotte ◽  
Monique Chagnon ◽  
Claude C�t� ◽  
Marie-Christine Thibault ◽  
Marcel R. Boulay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Genetic Polymorphism ◽  
Human Skeletal Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Muscle Enzymes ◽  
Acid Cycle

Effects of iron deficiency and training on mitochondrial enzymes in skeletal muscle

1987 ◽  
Vol 62 (6) ◽  
pp. 2442-2446 ◽  
Author(s):  
W. T. Willis ◽  
G. A. Brooks ◽  
S. A. Henderson ◽  
P. R. Dallman
Keyword(s):  
Skeletal Muscle ◽  
Iron Deficiency ◽  
Cytochrome C ◽  
Endurance Training ◽  
Tricarboxylic Acid Cycle ◽  
Interactive Effect ◽  
Tricarboxylic Acid ◽  
Mitochondrial Enzymes ◽  
Acid Cycle ◽  
Iron Deficient

We measured mitochondrial enzyme activities in skeletal muscle under conditions of iron deficiency and endurance training to assess the effects of these interventions on the contents and proportions of non-iron-containing and iron-dependent enzymes and proteins. Male Sprague-Dawley rats, 21 days of age, received a diet containing either 6 (iron deficient) or 50 mg iron/kg diet (iron sufficient). At 35 days of age animals were subdivided into sedentary and endurance training groups (running at 0.7 mph, 0% grade, 45 min/day, 6 days/wk). By 70 days of age, iron deficiency had decreased gastrocnemius muscle cytochrome c by 62% in sedentary animals. In contrast, the activities of tricarboxylic acid cycle enzymes were increased, remained unchanged or were slightly decreased, indicating that iron deficiency markedly altered mitochondrial composition. Endurance training increased cytochrome c (35%), tricarboxylic acid cycle enzymes (approximately 15%), and manganese superoxide dismutase (33%) in iron-deficient rats, whereas the same exercise regimen had no effect on the skeletal muscle of iron-sufficient animals. The interactive effect of dietary iron deficiency and mild exercise on mitochondrial enzymes suggests that adaptation to a training stimulus is, to some extent, geared to the relationship between the energy demand of exercise and the capacity for O2 transport and utilization.

Epinephrine increases tricarboxylic acid cycle intermediates in human skeletal muscle

1991 ◽  
Vol 260 (3) ◽  
pp. E436-E439 ◽  
Author(s):  
M. K. Spencer ◽  
A. Katz ◽  
I. Raz
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Adenine Nucleotides ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Quadriceps Femoris Muscle ◽  
Before And After ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Femoris Muscle

The effects of epinephrine (E) and insulin infusions on the contents of tricarboxylic acid cycle intermediates (TCAI), adenine nucleotides and their catabolites, and amino acids in skeletal muscle have been investigated. Eight men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1) and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. The sum of citrate, malate, and fumarate in muscle did not change significantly during UH (P greater than 0.05) but doubled during UHE (P less than 0.001). There were no significant changes in any of the adenine nucleotides, their catabolites (including inosine monophosphate), or aspartate during UH and UHE (P greater than 0.05); nor were there any significant changes in pyruvate or alanine contents during UH (P greater than 0.05). On the other hand, there were significant increases in pyruvate and alanine contents during UHE (P less than 0.01 and 0.05, respectively), suggesting that there was increased production of 2-oxoglutarate (a TCAI) via the alanine aminotransferase (ALT) reaction. It is concluded that E infusion increases the contents of TCAI in human skeletal muscle, and it is likely that at least part of the increase is attributable to increased flux through the ALT reaction.

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