Alkaptonuria(Black Urine Disease)

By: Rebecca MartinKrista Blackwell

Krysten LaFountain-PavlakVeronica Jones

WHAT IS IT?

• Rare, recessive, genetic disorder • Caused by genetic mutation to

homogentisate 1,2-dioxygenase gene (HGD gene)

• 1/250,000 affected (AKU Brochure, 2010) • Homogentisate dioxygenase enzyme

cannot breakdown homogentisic acid from Phenylalanine and Tyrosine

• Not a well known diseaseAKU. Liverpool : Alkaptonuria Society, 2006. Print.

Metabolic Pathway

• Homogentisate dioxygenase (enzyme) breaks down Phenylalanine and Tyrosine– Pathway not working, can’t break down

Amino Acids• Without breakdown, phenylalanine and

tyrosine accumulate in connective tissues – Ochronosis– i.e. cartilage

Genetics Home Reference, 2010.AKU. Liverpool : Alkaptonuria Society, 2006. Print.

METABOLIC PATHWAY http://www.google.com/imgres?imgurl=http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi%3Fbook%3Dgene%26part%3Dalkap%26blobname%3DalkapFig1.jpg&imgrefurl=http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi%3Fbook%3Dgene%26part%3Dalkap&usg=__nINDz314Tuj61aTi9kfswFgZR1g=&h=451&w=575&sz=213&hl=en&start=0&zoom=1&tbnid=DT46oUD0as8cpM:&tbnh=142&tbnw=181&prev=/images%3Fq%3DAlkaptonuria%2Bmetabolic%2Bpathway%26um%3D1%26hl%3Den%26client%3Dfirefox-a%26sa%3DN%26rls%3Dorg.mozilla:en-US:official%26biw%3D1280%26bih%3D589%26tbs%3Disch:1&um=1&itbs=1&iact=hc&vpx=334&vpy=79&dur=2463&hovh=199&hovw=254&tx=74&ty=222&ei=xRvUTPf1AsL58Aaq7_26BQ&oei=xRvUTPf1AsL58Aaq7_26BQ&esq=1&page=1&ndsp=18&ved=1t:429,r:1,s:0

http://memo.cgu.edu.tw/chia-chu/c6.html

Phenylalanine & Tyrosine Catabolic Pathway

Isomerase

Oxidoreductase

Oxidoreductase

Hydrolase

http://www.elmhurst.edu/~chm/vchembook/635pku.html

http://umbbd.msi.umn.edu/core/graphics/c0109.gif

4-Fumarylacetoacetate

Fumarate Acetoacetate

http://umbbd.msi.umn.edu/core/graphics/c0069.gif http://

umbbd.msi.umn.edu/core/graphics/c0111.gif

Symptomshttp://mizzouderm.com/uploads/4/4/2/3/4423869/7790022.jpg?237Color change in Connective Tissue (cartilage)

http://bjo.bmj.com/content/83/6/680/F1.large.jpg Ochronosis in Eye sclera

•Dark brown, black, blue urine•Arthritis•Kidney stones•Prostate stones•Heart problems•Darkening of ear•Dark spots in white of eyes (Ochronosis)•Hardening of blood valves•Build-up of fats and cholesterol in blood•Brittle bones•Build-up of pigments in respiratory system (leads to troubled breathing)

AKU. Liverpool : Alkaptonuria Society, 2006. Print.

SymptomsA: Normal UrineB: Urine from patient with AKUBlack urine results from exposure to Oxygen

http://www.clinmedres.org/content/vol2/issue4/images/large/209.fig3.jpeg

Treatments• No known cure• Low protein diet• Vitamin C• Clinical Testing: Nitisione (herbicide)– Reduces acid production– Currently undergoing Clinical Testing– Results have proven to reduce acid

buildup by 95% (short-term studies)

Alkaptonuria Society, 2006

WORKS CITED:• AKU. Liverpool : Alkaptonuria Society, 2006. Print. • U.S. National Library of Medicine. 2010. Genetics

Home Reference. Alkaptonuria. http://ghr.nlm.nih.gov/condition/alkaptonuria

• 2010. Photograph. University of Minnesota: Biocatalysis/Biodegredation Database. http://umbbd.msi.umn.edu/