MORPHOLOGIC ASPECTS OF MUSCLE BREAKDOWN AND LYSOSOMAL ACTIVATION

The aim of this review is to summarize and discuss recent findings and new insights in the etiology and phenotype of metabolic myopathies. The review relies on a systematic literature review of recent publications. Metabolic myopathies are a heterogeneous group of disorders characterized by mostly inherited defects of enzymatic pathways involved in muscle cell metabolism. Metabolic myopathies present with either permanent (fixed) or episodic abnormalities, such as weakness, wasting, exercise-intolerance, myalgia, or an increase of muscle breakdown products (creatine-kinase, myoglobin) during exercise. Though limb and respiratory muscles are most frequently affected, facial, extra-ocular, and axial muscles may be occasionally also involved. Age at onset and prognosis vary considerably. There are multiple disease mechanisms and the pathophysiology is complex. Genes most recently related to metabolic myopathy include PGM1, GYG1, RBCK1, VMA21, MTO1, KARS, and ISCA2. The number of metabolic myopathies is steadily increasing. There is limited evidence from the literature that could guide diagnosis and treatment of metabolic myopathies. Treatment is limited to mainly non-invasive or invasive symptomatic measures. In conclusion, the field of metabolic myopathies is evolving with the more widespread availability and application of next generation sequencing technologies worldwide. This will broaden the knowledge about pathophysiology and putative therapeutic strategies for this group of neuromuscular disorders.

Download Full-text

An Outbreak of Muscle Breakdown

Current Sports Medicine Reports ◽

10.1249/jsr.0b013e3181fc6d1a ◽

2010 ◽

Vol 9 (6) ◽

pp. 325-326 ◽

Cited By ~ 5

Author(s):

E. Randy Eichner

Keyword(s):

Muscle Breakdown

Download Full-text

Interaction between pyridine nucleotide coenzymes and heme proteins as a possible source of error in assay of activities of coenzyme-linked enzyme.

Clinical Chemistry ◽

10.1093/clinchem/35.10.2129 ◽

1989 ◽

Vol 35 (10) ◽

pp. 2129-2133 ◽

Cited By ~ 1

Author(s):

M D Jeyasingham ◽

O E Pratt ◽

H K Roopral

Keyword(s):

Pyridine Nucleotide ◽

Peak Height ◽

Heme Group ◽

Ultraviolet Absorbance ◽

The Third ◽

Spectral Shifts ◽

Muscle Breakdown ◽

Activity Of Enzymes ◽

Source Of Error ◽

Absorbance Spectra

Abstract The ultraviolet absorbance spectra of pyridine nucleotide coenzymes change in the presence of heme-containing proteins. The positions of each of the two main absorbance peaks of NADH are shifted progressively towards shorter wavelengths in the presence of increasing concentrations of hemoglobin, and the third peak, at 220 nm, disappears altogether. Similar changes are seen in the spectra of NAD+ and NADPH, and similar effects on these spectra are produced by myoglobin and cytochrome c, but not by comparable concentrations of albumin. The spectral shifts are generally accompanied by a decreased peak height. This finding may help explain problems reported by previous workers in the measurement of the activity of enzymes such as transketolase or lactate dehydrogenase in erythrocyte hemolysates. Errors may be considerable if allowance is not made for this effect, especially if the concentration of heme protein in the spectrophotometer cuvette much exceeds 1 g/L. The interaction appears to indicate some form of bonding, occurring generally between pyridine nucleotide coenzymes and the heme group in proteins. We relate the findings to measurement of activities of pyridine nucleotide-linked enzymes in erythrocyte lysates and in plasma containing myoglobin after muscle breakdown.

Download Full-text

Muscle wasting in the critically ill patient: how to minimise subsequent disability

British Journal of Hospital Medicine ◽

10.12968/hmed.2020.0045 ◽

2020 ◽

Vol 81 (4) ◽

pp. 1-9

Author(s):

Luke Flower ◽

Zudin Puthucheary

Keyword(s):

Critically Ill ◽

Psychological Health ◽

Critically Ill Patients ◽

Muscle Wasting ◽

Critically Ill Patient ◽

Muscle Loss ◽

Post Discharge ◽

Mortality And Morbidity ◽

Muscle Breakdown ◽

Physical And Psychological Health

Muscle wasting in critically ill patients is the most common complication associated with critical care. It has significant effects on physical and psychological health, mortality and quality of life. It is most severe in the first few days of illness and in the most critically unwell patients, with muscle loss estimated to occur at 2–3% per day. This muscle loss is likely a result of a reduction in protein synthesis relative to muscle breakdown, resulting in altered protein homeostasis. The associated weakness is associated with in an increase in both short- and long-term mortality and morbidity, with these detrimental effects demonstrated up to 5 years post discharge. This article highlights the significant impact that muscle wasting has on critically ill patients' outcomes, how this can be reduced, and how this might change in the future.

Download Full-text