P-Amino hippurate

In addition to its content in the glomerular filtrate, the marker is secreted by the renal tubule. Its clearance rate is used to measure renal blood flow but it overestimates the GFR. The aniline derivatives,p-amino hippurate (PAH) or radiolabeled o-iodohippuxan (OIH), represent this group of renal markers. Note that PAH is partly filtered by the glomerular membrane, but molecules that are exclusively excreted by the renal tubules would be ideal for renal blood flow measurements. 

Plasma protein-bound drugs that are substrates for transport carriers can be cleared from blood at high velocity e.g., p-amino-hippurate by the renal tubule and sulfo-bromophthalein by the liver. Clearance rates of these substances can be used to determine renal or hepatic blood flow. 

D. Pritchard, Luminal and peritubular steps in renal transport of p amino-hippurate, Biochim. Biophys. Acta, 906 295-309 (1987). 

Back S-E, Ljungberg B, Nilsson-Ehle I, Borga O, Nhsson-Ehle P. Age dependence of renal function clearance of iohexol and p-amino hippurate in healthy males. Scand J Clin Lab Invest 1989 49 641-6. 

ORGANIC ANION TRANSPORT Structurally diverse organic anions are secreted in the proximal tubule. The primary function of organic anion secretion appears to be the removal from the body of xenobiotics, including many weakly acidic drugs (e.g., pravastatin, captopril, p-amino-hippurate [PAH], and penicillins) and toxins (e.g., ochratoxin). 

Essig A, Competitive inhibition of renal transport of p-amino-hippurate by analogs of chlorothiazide. Am. /. Physiol., 201, 303-308 (1961) Chamicki WP, Bacher FA, Freeman SA and DeCesare DH, The pharmacy of chlorothiazide A new orally effective diuretic agent, /. Am. Pharm. Assoc., Sci Edn., 48, 656-659 (1959). 

The nephrotoxicity associated with the use of amphotericin B was found to vary with individual susceptibility, not dose.9o jjjg adverse effects of amphotericin B on renal function have been summarized.97 The inhibition of p-amino-hippuric acid (PAH) transport in rat kidney by amphotericin B may reflect on the significance of renal blood measurements.9 Amphotericin B is cleared from cerebrospinal fluid by simple diffusion and not an active transport mechanism.99 Combination therapy of amphotericin B and sulfonamides resulted in a high frequency of patient intolerance. Close attention to fungal pathogen inhibitory values and peak serum levels permitted less amphotericin B to be used with less toxicity. ... 

Inhibitor Glutamo-amide transfer Synthesis of hippuric acid or of p-amino-hippuric acid Synthesis of glutathione Amino acid Synthesis incor-of serum poraton albumin ... 

The enzymes for the synthesis of hippuric acid and for p-amino-hippuric acid have been localized as almost entirely in mitochondria (79). In the synthesis of hippuric acid benzoic acid can be replaced by some other aromatic and heterocyclic carboxylic acids (phenylacetic and cholic acids were inactive), glycine could not be replaced by either iS-alanine or taurine (100). 

In addition to this, the simplest method of synthesising a-amino-acids (a method which is less satisfactory for the preparation of higher members of the series), there are two other processes, both starting from aldehydes. Strecker obtained the nitrile of the amino-acid, Chap. V. 7, p. 229, by addition of ammonium cyanide to the next lower aldehyde, and Erlenmeyer jun. condensed hippuric acid with the aldehyde containing two carbon atoms less than the required amino-acid. 

Hippuric Acid.—When the benzoyl group is introduced into an amino acid in place of an amino hydrogen, by means of the Schotten-Baumann reaction, a benzoyl amino acid is obtained. With amino acetic acid or glycine (p. 388) the product is benzoyl amino acetic acid or benzoyl glycine, also known as hippuric acid. 

So, when p-methoxybenzaldehyde is allowed to react with hippuric acid (N-benzoylglycine), not only does aldol condensation occur but the product of that condensation is also subject to cyclization to an azlactone. Reduction and hydrolysis of the azlactone (oxazolone) produces an amino acid and benzoic acid, and, since a methoxy group is present in this particular synthesis, its cleavage is required and thus reduction here was effected with red phosphorus and HI. These reactions are shown in Scheme 12.43. 

---