Homogentisate

C. Excreted in the urine in the rare hereditary disease alkaptonuria. Homogentisic acid is easily oxidized in the air to dark-coloured polymeric products, so that urine from patients with alkaptonuria turns gradually black. It is formed from tyrosine and is an intermediate in tyrosine breakdown in the body. Alkaptonuria is due to the absence of the liver enzyme which cleaves the aromatic ring. 

Self-Test 10.10B The pH of a 0.50 m aqueous solution of the metabolic intermediate homogentisic acid is 2.35. What is the K, of homogentisic acid, C7Hs(OH)2COOH ... 

Heterocyclics 252, 260, 299,416 n-Hexadecanol esters 63 Hexaporphyrin 102 Hexitols 426 Hexobarbital 254,255 Hexoses 161,202 Hexuronic acid 158 Histamine 294,296, 355 Homogentisic acid 166,167 Horizontal chamber 127 Hotplates 93 ff -, temperature distribution 95 Hydrazines 269,284 Hydrazone formation 71 ff -with 2,4-dinitrophenylhydrazine 71, 72, 274... 

Examples include the liver enzymes, homogentisate dioxygenase (oxidase) and 3-hydroxyantliranilate dioxygenase (oxidase), that contain iron and L-trypto-phan dioxygenase (tryptophan pyrrolase) (Chapter 30), that utilizes heme. 

Tyrosine. Figure 30-12 diagrams the conversion of tyrosine to amphibolic intermediates. Since ascorbate is the reductant for conversion of y>-hydroxyphenylpyru-vate to homogentisate, scorbutic patients excrete incompletely oxidized products of tyrosine catabohsm. Subsequent catabohsm forms maleylacetoacetate, fu-marylacetoacetate, fumarate, acetoacetate, and ultimately acetyl-CoA>... 

Arias-Barrau E, ER Olivera, JM Lnengo, C Eemandez, B Galan, JL Garcia, E Dfaz, B Minambres (2004) The homogentisate pathway a central catabolic pathway involved in the degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in Pseudomonas putida J Bacterial 186 5062-5077. 

Denoya CD, DD Skinner, MR Morgenstern (1994) A Streptomyces avermitilis gene encoding a 4-hydroxy-phenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli. J Bacterial 176 5312-5319. 

Lindblad B, G Lindstedt, S Lindsted (1970) The mechanism of enzymatic formation of homogentisate from / -hydroxyphenylpyruvate. J Am Chem Soc 92 7446-7449. 

Homogentisic acid (2,5-dihydroxyphenylacetic acid, HGA) +0.45 glassy carbon t... 

One of the classical studies made by Garrod was of alcaptonuria. Here the abnormality, in which the urine turns black soon after voiding, although disconcerting, has only slight effects on the patient. The compound responsible is homogentisic acid. Phenylalanine, tyrosine,... 

Accumulation of homogentisic add in the blood causes its excretion in urine, after which it gradually darkens upon exposure to air. This sign of alcaptonuria is not present in all patients with the enzyme defidency. The dark pigment also accumulates over years in the cartilage (ochronosis), and most patients develop arthritis in adulthood. 

Answer A. Adults with alcaptonuria show a high prevalence of ochronotic arthritis due to deficiency of homogentisate oxidase. 

Brushtail possum Tridwsurus vulpecula Sternal gland Eucalyptus leaves 5-Methyl-2-furoic acid, homogentisic acid... 

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

Fig. 5. Metabolism of labeled phenylalanine p-HPP,p-hydroxyphenylalanine DHPA, 2,5-dihy-droxyphenylacetic acid (homogentisate)...

This enzyme [EC 1.13.11.5], an iron-dependent system (also called homogentisicase and homogentisate oxygenase), catalyzes the reaction of homogentisate with dioxygen to produce 4-maleylacetoacetate. 

HOMOCYSTEINE S-METHYLTRANSEERASE HOMOGENEOUS CATALYSIS HOMOGENEOUS REACTION HOMOGENTISATE 1,2-DIOXYGENASE HOMOISOGITRATE DEHYDROGENASE Homoleptic,... 

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