Time courses of changes ofpara-,meta-, andortho-tyrosine in septic patients: A pilot study

Szélig, Lívia; Kun, Szilárd; Woth, Gábor; Molnár, Gergő Attila; Zrínyi, Zita; Kátai, Emese; Lantos, János; Wittmann, István; Bogár, Lajos; Miseta, Attila; Csontos, Csaba

doi:10.1179/1351000215y.0000000028

Cited by 10 publications

(16 citation statements)

References 34 publications

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“…While the renal excretion of p -tyrosine does not significantly differ in these disease states compared to healthy controls (median FE in CKD = 1.36%; in diabetes = 0.98%; in CKD and diabetes = 1.06%), there is a marked increase in the renal excretion of o -tyrosine in patients with these diseases (median FE in CKD = 27.28%; in diabetes = 125.29%; in CKD and diabetes = 111.89%); although it should be noted that in patients with chronic kidney disease alone these values failed to reach significance (Molnar et al, 2005b). Recently similar results were also reported in septic patients with the fractional excretion of m -tyrosine (mean FE = 61.0%) and o -tyrosine (mean FE = 243%) being significantly greater than that of p -tyrosine (mean FE = 1.6%) (Szelig et al, 2015). It is, however, unclear whether these results represent an adaptation of the kidneys to preferentially clear m - and o -tyrosine under conditions that are potentially favorable for the production of the abnormal tyrosine isomers, a reflection of some aspect of kidney damage in these diseases, or whether this could represent in loco production of the abnormal tyrosine isomers within the kidney during diseased states.…”

Section: How Could Tyrosine Isomers Contribute To the Adverse Effesupporting

confidence: 73%

Roles of the tyrosine isomers meta- tyrosine and ortho- tyrosine in oxidative stress

Ipson

Fisher

2016

Ageing Research Reviews

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The damage to cellular components by reactive oxygen species, termed oxidative stress, both increases with age and likely contributes to age-related diseases including Alzheimer’s disease, atherosclerosis, diabetes, and cataract formation. In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring of the amino acid phenylalanine, which then produces the abnormal tyrosine isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o-tyrosine concentrations have been used as a biological marker of oxidative stress, there is emerging evidence from bacterial, plant, and mammalian studies demonstrating that these isomers, particularly m-tyrosine, directly produce adverse effects to cells and tissues. These new findings suggest that the abnormal tyrosine isomers could in fact represent mediators of the effects of oxidative stress. Consequently the accumulation of m- and o-tyrosine may disrupt cellular homeostasis and contribute to disease pathogenesis, and as result, effective defenses against oxidative stress can encompass not only the elimination of reactive oxygen species but also the metabolism and ultimately the removal of the abnormal tyrosine isomers from the cellular amino acid pool. Future research in this area is needed to clarify the biologic mechanisms by which the tyrosine isomers damage cells and disrupt the function of tissues and organs, and to identify the metabolic pathways involved in removing the accumulated isomers after exposure to oxidative stress.

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Section: How Could Tyrosine Isomers Contribute To the Adverse Effesupporting

confidence: 73%

Roles of the tyrosine isomers meta- tyrosine and ortho- tyrosine in oxidative stress

Ipson

Fisher

2016

Ageing Research Reviews

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“…Supporting these data, a study in patients with sepsis found that changes in inflammatory markers (CRP and procalcitonin - PCT) were paralleled by changes in serum levels of m-Tyr and urinary excretion of both m- and o-Tyr [ 53 ].…”

Section: Acute Diseases Associated With Oxidative Stressmentioning

confidence: 95%

“…However, p-Tyr could more effectively overcome the inhibition by o-Tyr than by m-Tyr [ 78 ]. In the study on septic patients, serum levels of m-Tyr seemed at least as high as that of o-Tyr, however, urinary concentration and fractional excretion of o-Tyr was markedly higher than that of m-Tyr in the patients [ 53 ]. In the study on glycemia in septic patients, serum m- and o-Tyr levels were identical, however urinary concentration, daily excretion, clearance and fractional excretion of o-Tyr were approx.…”

Section: Relative Abundance Of Tyrosine Isomers and Their Significancmentioning

confidence: 99%

“…The data suggest that o-Tyr is retained less efficiently by the kidney, in fact, some data support active secretion or in loco production of o-Tyr, e.g. in the kidney of patients with sepsis or diabetes [ 53 , 22 ]. Also, the biologic value and efficacy of m- and o-Tyr may not be equal, as suggested by data on glucose metabolism or inhibition of cell growth [ 54 , 78 , 85 , 86 ].…”

Section: Relative Abundance Of Tyrosine Isomers and Their Significancmentioning

confidence: 99%

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Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review

Molnár¹,

Kun²,

Sélley³

et al. 2016

CMC

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Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + ortho-tyrosine)/para-tyrosine proved to be markers of carbohydrate homeostasis.In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine.Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases.

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“…The interplay between malignant cells and surrounding stromal cells is a milestone for understanding the role of microenvironment in tumor progression [ 108 ]. In this context, an active network is regulated by signals driven by cytokines, chemokines, growth factors, inflammatory cells, immune cells and enzymes involved in stroma remodeling [ 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ].…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

Non-Melanoma Skin Cancers: Biological and Clinical Features

Cives

Mannavola

Lospalluti

et al. 2020

IJMS

117

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Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Merkel cell carcinoma (MCC). These neoplasms are highly diverse in their clinical presentation, as well as in their biological evolution. While the deregulation of the Hedgehog pathway is commonly observed in BCC, SCC and MCC are characterized by a strikingly elevated mutational and neoantigen burden. As result of our improved understanding of the biology of non-melanoma skin cancers, innovative treatment options including inhibitors of the Hedgehog pathway and immunotherapeutic agents have been recently investigated against these malignancies, leading to their approval by regulatory authorities. Herein, we review the most relevant biological and clinical features of NMSC, focusing on innovative treatment approaches.

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Time courses of changes ofpara-,meta-, andortho-tyrosine in septic patients: A pilot study

Cited by 10 publications

References 34 publications

Roles of the tyrosine isomers meta- tyrosine and ortho- tyrosine in oxidative stress

Roles of the tyrosine isomers meta- tyrosine and ortho- tyrosine in oxidative stress

Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review

Non-Melanoma Skin Cancers: Biological and Clinical Features

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