Transamination in Muscular Dystrophy and the Effect of Exogenous Glutamate: A Study on Vitamin E Deficient Rabbits, and Mice With Hereditary Dystrophy

Laferte, Roland O.; Rosenkrantz, Harris; Berlinguet, Louis

doi:10.1139/y63-162

Cited by 7 publications

(8 citation statements)

References 8 publications

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“…The loss of A1AT activity was more than that of AAT suggesting that the former was greatly affected on denervation. The skeletal muscle of vitamin E deficient rabbits at the severe stage of the dystrophic process had also been observed to exhibit such greater loss of A1AT than AAT [22]. The aminotransferase activities in different tissues and serum of normal and denervated frogs were similar (table II).…”

Section: Resultsmentioning

confidence: 89%

“…Previous investigations on the amino transferase activities of the vitamin E deficient rabbits and mice with hereditary muscular dystrophy indicated that both the AAT and A1AT activities of skeletal muscle were slightly elevated at the pre liminary stage and considerably decreased at the acute stage of the dystrophic process [22]. The observed decrement in the level of amino transferase activities in frog muscle denervated for 1 month in the present study may represent the acute stage of the dystrophic pro cess as observed in rabbits and mice [22]. But the serum aminotrans ferase levels were found to be significantly elevated in the dystrophic animals with a concomitant decrease in the skeletal muscle.…”

Section: Discussionmentioning

confidence: 97%

“…But the serum aminotrans ferase levels were found to be significantly elevated in the dystrophic animals with a concomitant decrease in the skeletal muscle. The increased serum enzyme levels were presumed to be due to the leakage of the enzymes into the serum from the disintegrating muscle fibers [22,30]. Further, dystrophic mice showed a significant increase in liver A1AT activity and this was thought to be due to the greater synthesis of the enzyme in liver in a bid to compensate for the loss of the enzyme in muscle [22].…”

Section: Discussionmentioning

confidence: 99%

“…The increased serum enzyme levels were presumed to be due to the leakage of the enzymes into the serum from the disintegrating muscle fibers [22,30]. Further, dystrophic mice showed a significant increase in liver A1AT activity and this was thought to be due to the greater synthesis of the enzyme in liver in a bid to compensate for the loss of the enzyme in muscle [22]. To test such possibility, the amino transferase activities were determined in different tissues and serum of the denervated frog.…”

Section: Discussionmentioning

confidence: 99%

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Aminotransferase Activity in Denervation Atrophy of the Amphibian Skeletal Muscle

Nb¹

1971

Enzyme

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The activity levels and some properties of aspartate aminotransferase and alanine aminotransferase of normal and denervated frog skeletal muscle were investigated. In general, the denervated muscle showed significant decrement in the activities of the two aminotransferases. But the peripheral nerve section did not induce any change in the aminotransferase levels of fiver, kidney, heart and serum of frog. In the skeletal muscle, the two aminotransferases were found to exist in two different isozymes, one being associated with the mitochondria and the other with the soluble fraction. The mitochondrial component of both the enzymes was relatively cationic in nature when compared to the soluble fraction. The denervated muscle showed a considerable decrease in both the isozymes of the two aminotransferases. The thermostability of both the enzymes was considerably lowered in the denervated muscle. No elevation of either aminotransferase activity was observed in the denervated skeletal muscle following addition of a heat-denatured serum, while a marked elevation was observed in the normal muscle. The enzymes of denervated muscle showed altered sensitivities towards their inhibitors. The results of the present study suggest that denervation induces quantitative as well as qualitative changes in the aminotransferases of frog skeletal muscle.

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Section: Resultsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aminotransferase Activity in Denervation Atrophy of the Amphibian Skeletal Muscle

Nb¹

1971

Enzyme

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“…Intracellular degradation of myofibrillar proteins also release glutamic acid with large amounts contributing to the muscle glutamic acid pool [ 26 ]. The role of glutamic acid in muscular dystrophy was studied in the early 1960s in rabbit models (due to vitamin E deprivation) [ 27 ]. In these studies, body weight loss and the onset of terminal disease was accelerated when animals were given exogenous glutamic acid [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

et al. 2017

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Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two pathways, inosine-5′-monophosphate (VIP Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the LDE signature, with two metabolites (phosphoglyceric acid and inosine-5′-monophosphate) being significantly decreased. When the BF and LDE were compared, the most significant metabolite was phosphoric acid, which was significantly less in the GRMD BF compared to control and GRMD LDE groups. Conclusions: The identification of elevated BF oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in arginine and proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease. Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes.

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Aldolase Activity in Normal and Dystrophic Mouse Muscle

Srivastava¹,

Berlinguet²

1964

Can. J. Biochem.

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Aldolase activity and nitrogen content of the muscle were deteriniiled in hereditary muscular dystrophic mice and their normal litter mates a t various ages. Aldolase activity was found to decrease in dystrophic muscle when expressed per mg of wet tissue but showed an increase a t later stages of the disease when expressed per mg of total nitrogen in muscle. Total nitrogen content of dystrophic muscle decreased considerably during the evolution of the disease. In normal mice, the muscle aldolase activity increases with age.

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Transamination in Muscular Dystrophy and the Effect of Exogenous Glutamate: A Study on Vitamin E Deficient Rabbits, and Mice With Hereditary Dystrophy

Cited by 7 publications

References 8 publications

Aminotransferase Activity in Denervation Atrophy of the Amphibian Skeletal Muscle

Aminotransferase Activity in Denervation Atrophy of the Amphibian Skeletal Muscle

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

Aldolase Activity in Normal and Dystrophic Mouse Muscle

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