Biochemistry Class notes

Aminoacidurias: 

Amino acids are also entirely reabsorbed in PCT. There are 5 independent proximal tubular transport processes for amino acids, including those for

1.      Basic amino acids plus cysteine

2.      Glutamic and aspartic acid

3.      Neutral amino acids

4.      Imino acids and

5.      Glycine.  

Aminoacidurias can be overflow, glomerular, tubular and nephrogenic or secretory.

Cystinuria: 

It is a classic example of an amino aciduria due to true defect in renal tubular function. In most cases of cystinuria other dibasic amino acids like ornithine, arginine and lysine are also lost. The only known clinical manifestation of cystinuria is recurrent urinary calculi, the name cysteine coming from original (erroneous) assumption that the source of these stone was the bladder. Cystine stones form readily in acidic urine. 

They are yellow brown in color and are radio-opaque due to their sulphur content. These patients have higher incidence of calcium oxalate stones and all stone formers should be screened for cystinuria, preferably by formal amino acid measurement in the urine as qualitative screening test. This cystinuria is a metabolic disease and inheritance is autosomal recessive and individuals excrete cysteine, ornithine, arginine and lysine in urine. Defect or mutation in activator of amino acid transporter for cysteine and dibasic amino acids is found. Medical treatment of cystinuria begins with maintenance of high fluid intake throughout 24h and alkalinization of urine, both being aimed at decreasing the chance of precipitation of cysteine in the renal tract. Cystine solubilizing agent like D-penicillamine or chelating agent like captopril can be used. Otherwise cystinuria can damage kidney and result in CRF.

Cystine can be tested in urine by cynide-nitroprusside test, chromatographic techniques or other advanced techniques. In the cyanide-nitroprusside test, cysteine is split into two molecules of cysteine by cyanide. Sodium nitroprusside reacts with free sulfide groups to give a magenta color.

Hartnup disorder: 

In this condition there is also a true defect in renal tubular function. This is named after the family in which it was first described and is again a defect of both renal and intestinal amino acid transport. The feature is failure to reabsorb the neutral amino acids in renal tubule with their appearance in urine (E.g. Alanine, glycine, phenylalanine, tyrosine, asparagine, glutamine, etc). Most affected individual have increased amounts of indoles (e.g. indicant) in urine, which originates from the bacterial breakdown in the gut of unabsorbed tryptophan. There is pellagra like skin rash, renal amino aciduria and other features.

Dent’s disease:

It is X-linked nephrolithiasis, and is caused by mutation in gene coding for voltage gated chloride channel (CLC-5) expressed in PCT. The defect is thought to cause failure of the endosomal acidification that is required to allow recycling of the PCT membrane receptor megalin which mediates protein reabsorption. The syndrome is characterized by hypercalciuria, nephrocalcinosis, and LMW proteinuria.