Renal tubular transport and catabolism of proteins and peptides

Abstract

The kidney plays an important role in the metabolism of proteins and peptides. Current evidence indicates that only the proximal tubule possesses the mechanism for degradation or transport of these substances and reabsorption of metabolic products. Proteins and large polypeptides filtered at the glomerulus are absorbed from proximal tubular fluid by luminal endocytosis into apical vacuoles. These fuse with primary lysosomes, where hydrolysis occurs followed by diffusion of metabolites out of the cells and into the blood. Recent evidence indicates that small linear peptides are handled by a different mechanism. It is likely that small peptides are degraded at the luminal surface of the brush border of proximal tubules, which contains many hydrolytic enzymes, by the process of membrane or contact digestion with reabsorption of the breakdown products. The probable biological significance of proximal tubular mechanisms for handling of proteins and peptides are conservation of amino acids, inactivation of toxic substances, and participation in the regulation of the circulating level of protein and peptide hormones.

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study

“…NT-proBNP (8.5 kDa) is subsequently eliminated via the kidneys (7 ), whereas the elimination routes of cTnT and cTnI are unknown. However, based on their molecular weight, free cTnT (37 kDa), free cTnI (24 kDa), and their fragments may be (partly) filtered by the glomeruli and catabolized by the tubules (25,26 ). Indeed, after myocardial infarction, cTnT and cTnI have been observed as free cTnT and cTnI, larger cTnT-I-C (77 kDa) and cTnI-C (40 kDa) complexes, and fragments (27)(28)(29)(30)(31).…”

Cystatin C

“…Several authors have attempted to look for tubular secretion of low-molecular-weight proteins such as cystatin C. 59,60 In general, it appears that, in the absence of signi¢cant tubular damage, there is no passage of proteins such as cystatin C from the renal vasculature directly into the renal tubule. These data suggest that cystatin C is a plausible candidate for the assessment of GFR and that it o¡ers a number of physiological advantages over creatinine.…”

Pacifastin-derived Peptides Target Tumors for Use in In Vivo Imaging

“…However, THP1*-MMAE was ~1,000-fold less potent than MMAE alone at growth inhibition of Ramos cells with IC 50 values from 100-1,000 nM. This potency reduction is also seen with brentuximab vedotin, which sees potency losses of up to 30-fold in antigen-positive cells when compared with MMAE alone (26). In order to assess activity in models of chemotherapy resistance, we generated Ramos-250 and Ramos-1000 sublines (resistance to 250 nM and 1,000 nM doxorubicin, respectively) by continuouly exposing them to increasing concentrations of doxorubicin.…”

“…Additionally, tumor specific uptake had an 8.3-fold higher delivery to tumor than to liver. While THP1-AF647 has 60-fold higher fluorescent signal observed in the kidneys when compared with AF647 treated mice this accumulation is often seen following glomerular filtration of small peptides (26). To investigate the biodistribution of the THP1, both with and without conjugation to AF647, we evaluated a further modified form, termed THP1* and containing a single-lysine (K18), by using whole-body autoradiography.…”