Proline metabolism and cancer

Phang, James M.; Liu, Wei; Hancock, Chad N.; Fischer, Joseph W.

doi:10.1097/mco.0000000000000121

Cited by 205 publications

(136 citation statements)

References 38 publications

(57 reference statements)

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“…Fibrillary collagen synthesis, which is an important process in the proliferative phase of wound healing, requires the formation of proline and hydroxyproline [58]. Several other studies have shown that oxygen accelerates collagen synthesis and improves proline hydroxylase enzyme activity [59].…”

Section: Discussionmentioning

confidence: 99%

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

et al. 2016

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In this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+ O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF + O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF + O2 dressings improve re-epithelialization (p < 0.0001) and synthesis of collagen over controls (p < 0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF + O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF + O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology.

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Section: Discussionmentioning

confidence: 99%

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

et al. 2016

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“…In addition, Liu et al (34) showed that transcription factor MYC inhibits POX/PRODH expression and, thus, inhibits its function. microRNA miR-23b* an inhibitor of POX is highly expressed in different types of tumors (35,36). Due to the lack of POX, the conversion of proline to pyrroline-5-carboxylate (P5C) is altered (37), and subsequently the amount of proline in urine is increased.…”

Section: Resultsmentioning

confidence: 99%

Determination of common urine substances as an assay for improving prostate carcinoma diagnostics

et al. 2014

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Abstract.Recently, interest in the identification of non-invasive markers for prostate carcinoma detectable in the urine of patients has increased. In this study, we monitored the abundance of potential non-invasive markers of prostate carcinoma such as amino acid sarcosine, involved in the metabolism of amino acids and methylation processes, ongoing during the progression of prostate carcinoma. In addition, other potential prostate tumor markers were studied. The most significant markers, prostate-specific antigen (PSA) and free PSA (fPSA), already used in clinical diagnosis, were analyzed using an immunoenzymometric assay. Whole amino acid profiles were also determined to evaluate the status of amino acids in patient urine samples and to elucidate the possibility of their utilization for prostate carcinoma diagnosis. To obtain the maximum amount of information, the biochemical parameters were determined using various spectrophotometric methods. All results were subjected to statistical processing for revealing different correlations between the studied parameters. We observed alterations in most of the analyzed substances. Based on the results obtained, we concluded that the specificity of prostate carcinoma diagnosis could be improved by determination of common urine metabolites, since we compiled a set of tests, including the analysis of sarcosine, proline, PSA and uric acid in the urine. These metabolites were not observed in the urine obtained from healthy subjects, while their levels were elevated in all patients suffering from prostate carcinoma.

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“…3C). Interestingly, the glutamate derivatives proline, aspartate and glutathione are associated with proliferation and tumorigenesis (34–38). …”

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confidence: 99%

Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass

Spinelli

Yoon

Ringel

et al. 2017

Science

342

325

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Ammonia is a ubiquitous by-product of cellular metabolism, however the biological consequences of ammonia production are not fully understood, especially in cancer. We find that ammonia is not merely a toxic waste product, but is recycled into central amino acid metabolism to maximize nitrogen utilization. Cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH), and secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment, and was used directly to generate amino acids through GDH activity. These data show that ammonia not only is a secreted waste product, but a fundamental nitrogen source that can support tumor biomass.

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Proline metabolism and cancer

Cited by 205 publications

References 38 publications

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

Determination of common urine substances as an assay for improving prostate carcinoma diagnostics

Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass

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