Fatty acid binding to cytoplasmic proteins of myocardium and red and white skeletal muscle in the rat. A possible new role for myoglobin

Gloster, J; Harris, Peter

doi:10.1016/0006-291x(77)90333-3

Cited by 54 publications

(22 citation statements)

References 17 publications

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“…Unfortunately, fatty acid binding protein (FABP) has a molecular mass of 15kDa. FABP studies have determined that Mb binds to fatty acids with a lower affinity than albumin on a per-mole basis, with a Kd of 12.2 to 48moll -1 (Gloster, 1977;Gloster and Harris, 1977;Götz et al, 1994). However, other studies have refuted such findings (Glatz and Veerkamp, 1983;Said and Schulz, 1984).…”

Section: Fatty Acid Interaction With Mbmentioning

confidence: 86%

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Myoglobin's old and new clothes: from molecular structure to function in living cells

Gros

Wittenberg

Jue

2010

Journal of Experimental Biology

100

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SUMMARY Myoglobin, a mobile carrier of oxygen, is without a doubt an important player central to the physiological function of heart and skeletal muscle. Recently, researchers have surmounted technical challenges to measure Mb diffusion in the living cell. Their observations have stimulated a discussion about the relative contribution made by Mb-facilitated diffusion to the total oxygen flux. The calculation of the relative contribution, however, depends upon assumptions, the cell model and cell architecture, cell bioenergetics, oxygen supply and demand. The analysis suggests that important differences can be observed whether steady-state or transient conditions are considered. This article reviews the current evidence underlying the evaluation of the biophysical parameters of myoglobin-facilitated oxygen diffusion in cells, specifically the intracellular concentration of myoglobin, the intracellular diffusion coefficient of myoglobin and the intracellular myoglobin oxygen saturation. The review considers the role of myoglobin in oxygen transport in vertebrate heart and skeletal muscle, in the diving seal during apnea as well as the role of the analogous leghemoglobin of plants. The possible role of myoglobin in intracellular fatty acid transport is addressed. Finally, the recent measurements of myoglobin diffusion inside muscle cells are discussed in terms of their implications for cytoarchitecture and microviscosity in these cells and the identification of intracellular impediments to the diffusion of proteins inside cells. The recent experimental data then help to refine our understanding of Mb function and establish a basis for future investigation.

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Section: Fatty Acid Interaction With Mbmentioning

confidence: 86%

“…14 C oleic acid does bind to a rat heart cytosolic fraction of 16kDa. Because Mb has a molecular mass of 16kDa, the observation implicates Mb (Gloster and Harris, 1977). Unfortunately, fatty acid binding protein (FABP) has a molecular mass of 15kDa.…”

Section: Fatty Acid Interaction With Mbmentioning

confidence: 99%

Myoglobin's old and new clothes: from molecular structure to function in living cells

Gros

Wittenberg

Jue

2010

Journal of Experimental Biology

100

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“…We discovered that the co-localisation of Mb with FASN might give a hint towards the FA-binding function of tumour Mb. Fatty acid-binding properties of Mb have been reported and predicted early (Lewis et al, 1968;Gloster and Harris, 1977), and have recently gained further attention . According to Flögel et al (2005), lack of Mb in the heart of knockout mice leads to a biochemical shift in cardiac substrate utilisation from FA to glucose oxidation, which, not only corresponds to an adaptive reduction in O 2 consumption for the equimolar production of ATP but also implicates the protein in providing FA substrates for the mitochondrial b-oxidation breakdown in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…As this minute amount of Mb is unlikely to have a significant role in the maintenance of cellular oxygenation, Mb functions alternative to respiratory support have to be considered. Recently, Mb was described as a FA-binding protein and suggested to have a role in the transport of FAs in oxygenated cells (Gloster and Harris, 1977;Yackzan and Wingo, 1982;Masuda et al, 2008). This prompted us to investigate the possible co-localisation of Mb and FASN in both healthy and cancerous breast tissue.…”

Section: Non-respiratory Functions Of Non-muscle Mb?mentioning

confidence: 99%

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

et al. 2010

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BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-a (ERa)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1a (HIF-1a), HIF-2a, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERa or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2a and CAIX, but not to HIF-1a or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERa or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERa and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

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“…Indeed, early experiments have hinted at a fatty acid transport role for Mb. These experiments detected 14 C oleic acid binding to a rat heart cytosolic fraction of 16kDa, ascribed to Mb (Gloster and Harris, 1977). The binding to fatty acid exhibits on a per-mole basis a modest dissociation constant (K D ) of 12.2 to 48moll -1 (Gloster, 1977;Gloster and Harris, 1977;Gotz et al, 1994).…”

Section: Other Functions Of Mb Poresmentioning

confidence: 99%

‘It's hollow’: the function of pores within myoglobin

Tomita

Kreutzer

Adachi

et al. 2010

Journal of Experimental Biology

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SUMMARY Despite a century of research, the cellular function of myoglobin (Mb), the mechanism regulating oxygen (O2) transport in the cell and the structure–function relationship of Mb remain incompletely understood. In particular, the presence and function of pores within Mb have attracted much recent attention. These pores can bind to Xe as well as to other ligands. Indeed, recent cryogenic X-ray crystallographic studies using novel techniques have captured snapshots of carbon monoxide (CO) migrating through these pores. The observed movement of the CO molecule from the heme iron site to the internal cavities and the associated structural changes of the amino acid residues around the cavities confirm the integral role of the pores in forming a ligand migration pathway from the protein surface to the heme. These observations resolve a long-standing controversy – but how these pores affect the physiological function of Mb poses a striking question at the frontier of biology.

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Fatty acid binding to cytoplasmic proteins of myocardium and red and white skeletal muscle in the rat. A possible new role for myoglobin

Cited by 54 publications

References 17 publications

Myoglobin's old and new clothes: from molecular structure to function in living cells

Myoglobin's old and new clothes: from molecular structure to function in living cells

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

‘It's hollow’: the function of pores within myoglobin

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