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Analysis of Melanin-like Pigment Synthesized from Homogentisic Acid, with or without Tyrosine, and Its Implications in Alkaptonuria

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Analysis of Melanin-like Pigment Synthesized from Homogentisic Acid, with or without Tyrosine, and Its Implications in Alkaptonuria. / Taylor, Adam Michael; Vercruysse, Koen.
JIMD Reports. Vol. 35 Springer, 2017. p. 79-85 (JIMD Reports; Vol. 35).

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Taylor AM, Vercruysse K. Analysis of Melanin-like Pigment Synthesized from Homogentisic Acid, with or without Tyrosine, and Its Implications in Alkaptonuria. In JIMD Reports. Vol. 35. Springer. 2017. p. 79-85. (JIMD Reports). Epub 2016 Dec 10. doi: 10.1007/8904_2016_27

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@inbook{191e69dd3a7b4cc5b08bdac354ae6fae,
title = "Analysis of Melanin-like Pigment Synthesized from Homogentisic Acid, with or without Tyrosine, and Its Implications in Alkaptonuria",
abstract = "Alkaptonuria is an iconic disease used by Archibald Garrod to demonstrate the theory of “inborn errors of metabolism”. AKU knowledge has advanced in recent years; development of an in vitro model, discovery of murine models and advances in understanding bone and cartilage phenotypes and arthropathy in AKU. These discoveries have aided in a new clinical trial into nitisinone. However, there are still knowledge gaps surrounding the pigment in AKU and the pigmentation process. We demonstrate an advance in the understanding in the kinetics and chemistry of the polymerization of homogentisic acid (HGA) into its pigment using size exclusion chromatography and IR spectroscopy. We compared the properties of HGA-based pigments that were freshly prepared to those stored in solution for two years. Our results demonstrate the importance of pH in the polymerisation process and that colour change seen in solution (analogous to AKU patient urine) is not initially due to presence of ochronotic pigment but the quinone intermediary. In addition, we observed pigment formation from HGA can occur in the presence of tyrosine, without the inclusion of this tyrosine into the pigment. These observations have positive implications for patients with alkaptonuria; an increased understanding of the pigment polymer chemistry, the presence of an intermediary and their kinetics present more therapeutic opportunities for treating the condition, including preventing the pigment forming, binding or reversing established pigmentation. AKU patients treated with nitisinone show elevated tyrosine levels causing side effects such as corneal opacities, our data demonstrates that elevated tyrosine levels should not contribute or add to the ochronotic pigment burden in these patients. ",
keywords = "Alkaptonuria, Homogentisic acid , Pigment, Size-exclusion chromatography, Tyrosine",
author = "Taylor, {Adam Michael} and Koen Vercruysse",
year = "2017",
month = jan,
day = "1",
doi = "10.1007/8904_2016_27",
language = "English",
volume = "35",
series = "JIMD Reports",
publisher = "Springer",
pages = "79--85",
booktitle = "JIMD Reports",

}

RIS

TY - CHAP

T1 - Analysis of Melanin-like Pigment Synthesized from Homogentisic Acid, with or without Tyrosine, and Its Implications in Alkaptonuria

AU - Taylor, Adam Michael

AU - Vercruysse, Koen

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Alkaptonuria is an iconic disease used by Archibald Garrod to demonstrate the theory of “inborn errors of metabolism”. AKU knowledge has advanced in recent years; development of an in vitro model, discovery of murine models and advances in understanding bone and cartilage phenotypes and arthropathy in AKU. These discoveries have aided in a new clinical trial into nitisinone. However, there are still knowledge gaps surrounding the pigment in AKU and the pigmentation process. We demonstrate an advance in the understanding in the kinetics and chemistry of the polymerization of homogentisic acid (HGA) into its pigment using size exclusion chromatography and IR spectroscopy. We compared the properties of HGA-based pigments that were freshly prepared to those stored in solution for two years. Our results demonstrate the importance of pH in the polymerisation process and that colour change seen in solution (analogous to AKU patient urine) is not initially due to presence of ochronotic pigment but the quinone intermediary. In addition, we observed pigment formation from HGA can occur in the presence of tyrosine, without the inclusion of this tyrosine into the pigment. These observations have positive implications for patients with alkaptonuria; an increased understanding of the pigment polymer chemistry, the presence of an intermediary and their kinetics present more therapeutic opportunities for treating the condition, including preventing the pigment forming, binding or reversing established pigmentation. AKU patients treated with nitisinone show elevated tyrosine levels causing side effects such as corneal opacities, our data demonstrates that elevated tyrosine levels should not contribute or add to the ochronotic pigment burden in these patients.

AB - Alkaptonuria is an iconic disease used by Archibald Garrod to demonstrate the theory of “inborn errors of metabolism”. AKU knowledge has advanced in recent years; development of an in vitro model, discovery of murine models and advances in understanding bone and cartilage phenotypes and arthropathy in AKU. These discoveries have aided in a new clinical trial into nitisinone. However, there are still knowledge gaps surrounding the pigment in AKU and the pigmentation process. We demonstrate an advance in the understanding in the kinetics and chemistry of the polymerization of homogentisic acid (HGA) into its pigment using size exclusion chromatography and IR spectroscopy. We compared the properties of HGA-based pigments that were freshly prepared to those stored in solution for two years. Our results demonstrate the importance of pH in the polymerisation process and that colour change seen in solution (analogous to AKU patient urine) is not initially due to presence of ochronotic pigment but the quinone intermediary. In addition, we observed pigment formation from HGA can occur in the presence of tyrosine, without the inclusion of this tyrosine into the pigment. These observations have positive implications for patients with alkaptonuria; an increased understanding of the pigment polymer chemistry, the presence of an intermediary and their kinetics present more therapeutic opportunities for treating the condition, including preventing the pigment forming, binding or reversing established pigmentation. AKU patients treated with nitisinone show elevated tyrosine levels causing side effects such as corneal opacities, our data demonstrates that elevated tyrosine levels should not contribute or add to the ochronotic pigment burden in these patients.

KW - Alkaptonuria

KW - Homogentisic acid

KW - Pigment

KW - Size-exclusion chromatography

KW - Tyrosine

U2 - 10.1007/8904_2016_27

DO - 10.1007/8904_2016_27

M3 - Chapter

VL - 35

T3 - JIMD Reports

SP - 79

EP - 85

BT - JIMD Reports

PB - Springer

ER -