Kidneys flavins

Krause, R.J., Lash, L.H., and Elfarra, A.A. (2003) Human kidney flavin-containing monooxygenases (FMOs) and their potential roles in cysteine S-conjugate metabohsm and nephrotoxicity. J. Pharmacol. Exp. Ther. 304,185-191. 

While their physiologic role is uncertain, L-amino acid oxidases of liver and kidney convert amino acids to an a-imino acid that decomposes to an a-keto acid with release of ammonium ion (Figure 29-6). The reduced flavin is reoxidized by molecular oxygen, forming hy-... 

Hamman MA, Haehner-Daniels BD, Wrighton SA, et al. Stereoselective sulfoxidation of sulin-dac sulfide by flavin-containing monooxygenases. Comparison of human liver and kidney microsomes and mammalian enzymes. Biochem Pharmacol 2000 60(1) 7-17. 

Flavin Coenzymes.—5-Deazaflavin-adenine dinucleotide (2) can be prepared from the 5-deazaFMN,21 using a FAD pyrophosphorylase from rat liver.22 When the apoprotein of D-amino-acid oxidase from pig kidney is reconstituted with (2), no oxidation of D-alanine is observed, although the flavin chromophore in the reconstituted enzyme is reduced on the addition of DL-amino-acids.22 This has been interpreted as indicating that hydrogen transfer from the amino-acid to (2) can still... 

It is highly protein bound (approx. 96%), metabolised in the liver by N-oxidation to inactive metabolites by the enzyme flavin-containing monooxygenase. It is excreted mainly by the kidneys in the form of metabolites and as unchanged drug. 

The attention of biochemists was first attracted to flavins as a result of their color and fluorescence. The study of spectral properties of flavins (Fig. 15-8) has been of importance in understanding these coenzymes. The biochemical role of the flavin coenzymes was first recognized through studies of the "old yellow enzyme"144 145 which was shown by Theorell to contain riboflavin 5 -phosphate. By 1938, FAD was recognized as the coenzyme of a different yellow protein, D-amino acid oxidase of kidney tissue. Like the pyridine nucleotides, the new flavin coenzymes were reduced by dithionite to nearly colorless dihydro forms (Figs. 15-7 and 15-8) revealing the chemical basis for their function as hydrogen carriers. 

Nitroreductase activity has been demonstrated in liver homogenates as well as in the soluble fraction, whereas other studies have reported that nitroreductase activity has been found in all liver fractions evaluated. The reductase appears to be distributed in liver, kidney, lung, heart, and brain. The reaction utilizes both NADPH and NADH and requires anaerobic conditions. The reaction can be inhibited by the addition of oxygen. The reaction is stimulated by FMN and FAD, and at high flavin concentrations they can act simply as nonenzymatic electron donors. The reduction... 

The existence of choline dehydrogenase was first demonstrated by Mann and Quastel in 1937 247, 248) in extracts of rat liver and kidney. These authors also obtained evidence that the first oxidation product of choline was betaine aldehyde. Others showed subsequently that choline oxidase activity resided in the mitochondrial fraction of rat liver and is linked to the respiratory chain 249, 250). Detergents 251, 252), solvent treatment of fragmented mitochondria 253), and venom phospholipase 254-256) have been used for extraction and solubilization of choline dehydrogenase. Among these, the best method reported to date appears to be the digestion of acetone-powdered mitochondria with venom phospholipase. Choline dehydrogenase, partially purified from phospholipase extracts of rat liver mitochondria, contains 1 mole of flavin and 4 g-atoms of nonheme iron per 850,000 g protein. The flavin is claimed to be acid-... 

Rich sources of the coenzyme forms of the vitamin are liver, kidney, and heart. Many vegetables are also good sources, but cereals are rather low in flavin content. However, current practices of fortification and enrichment of cereal products have made these significant contributors to the daily requirement. Milk, from cows ° and humans, is a good source of the vitamin, but considerable loss can occur from exposure to light during pasteurization and bottling or as a result of irradiation to increase the vitamin D content. 

An enzyme that catalyzes the deamination of a-ami-no acids by dehydrogenation to keto acids and ammonia. Two types are recognized, acting on the d-and L-amino acids. Recent emphasis has been on characterization of the D-amino oxidase, which is known to contain the flavin isoalloxazine as coenzyme. Both types are found in animal tissue, especially in liver and kidney, as well as in snake venom and certain bacteria. 

High levels of D-amino acid oxidases are found in the liver and kidney. The enzyme contains flavin adenine dinucleotide (FAD) and deaminates many D-amino acids and... 

L-Amino add oxidases. Small amounts of ammonia are generated by various L-amino acid oxidases, found in liver and kidney, that require a flavin mononucleotide (FMN) coenzyme. FMN is regenerated from FMNH2 by reacting with 02 to form H202. 

One class of mechanism-based MAO inhibitors includes the unsaturated alkylamines (propargylamine analogs) (Table II). Although the kinetics of enzyme inactivation for these compounds are consistent with a mechanism-based inhibitor, in only a few cases has the chemical mechanism and site of protein modification been determined. Pargyline (iV-benzyl-N-methyl-2-propynylamine) is a classic example. Pargyline reacts stoichiometrically and irreversibly with the MAO of bovine kidney, with protection from inactivation afforded by substrate benzylamine (91). Furthermore, the reaction involves bleaching of the FAD cofactor at 455 nm and the formation of a new absorbing species at 410 nm and a covalent adduct of inactivator with flavin cofactor (92). 

Wang et al. (2001) investigated the effect of salinity of water on the toxicity of aldicarb in fishes. Their stndies indicated that salinity-mediated enhancement of aldicarb toxicity was species-dependent. In rainbow tront, salinity increased the toxicity of aldicarb, the effect attribnted to greater sulfoxidation to aldicarb snlfoxide cansed by increased flavin-containing monooxygenase and the catalytic activities in microsomes of liver, gill and kidney of rainbow trout. 

The biosynthesis of flavocoenzymes is regulated by the supply of riboflavin, competition for ATP and hormonal balances. Increasing riboflavin concentrations in the intestinal lumen decreases the rate of vitamin absorption, while riboflavin deficiency leads to increased absorption efiiciency. The hormones thyroxine and triiodothyronine stimulate FMN and FAD synthesis in mammals by increasing the activity of flavokinase and for this reason hypothyroidism leads to reduced tissue levels of flavins. In the kidney, aldosterone promotes an increase in the activity of fla vokinase and therefore an increase of flavins. 

L-Amino Add Oxidase. In 1944 L-amino acid oxidases were described in 3 sources animal kidney, snake venom, and bacteria. The enzyme was also detected in animal liver. The purification from rat kidney required large amounts of tissue because of the low activity. A 200-fold purification gave a preparation believed to be essentially pure. This protein has a molecular weight somewhat over 120,000, and contains 2 flavin mononucleotides per mole. If the protein isolated is indeed the enzyme, it has one of the lowest turnover numbers determined only 6 molecules of amino acid are oxidized per molecule of protein per minute, whereas n-amino add oxidase has a turnover number of more than 1000. 

---