Peptide metabolism

Dyn is not yet known, it is likely that such changes reflect variations in the activity of the associated pathways. One possible explanation is that increases in neuropeptide tissue levels are due to decreased release of the transmitter, which dunmishes the extracellular peptide metabolism and results in accumulation of these peptide substances. Another possible contributing factor is a drug-related alteration in neuropeptide synthesis. For example, Bannon et al. (1987) reported that METH administration increased the quantity of striatal messenger RNA for the SP precursor preprotachykinin. Thus, increases in peptide synthesis might contribute to increases in peptide content caused by treatment with METH or the other amphetamine analogs. 

Hoang VD, Uchenna AR, Mark J, Renaat K, Norbert V (2002) Characterization of human nasal primary culture systems to investigate peptide metabolism. Int J Pharm 238 247-256. 

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

Another major site of peptide metabolism is the blood and especially blood serum and plasma. From an extensive compilation of peptide tm values (over 100 peptides, plus derivatized and cyclized analogues, D-amino acid stereoisomers, peptide bond isosteres, etc.), it appears that the differences between serum, heparinized plasma, and whole blood are fairly limited [161]. Interspecies differences are larger, particularly between humans and rats, with most human/rat t1/2 ratios ranging from 1 1 to 25 1 ... 

Lew, R.A. HPLC in the analysis of peptide metabolism. In HPLC of Peptides and Proteins Methods and Protocols Methods in Molecular Biology Aguilar, M.-I., Ed. Humana Press, 2003 Vol. 251, 275-290. 

Some horses exhibiting signs of photic headshaking respond favorably to treatment with the antihistamine drug cyproheptadine (Wilkins 1997). In addition to antihistaminic action, cyproheptadine has anticholinergic action and is a 5-hydroxytryptamine (serotonin) antagonist, altering proopiomelanocortin peptide metabolism... 

K Zheng, X Liang, DT Rossi, GD Nordblom, CM Barksdale, D Lubman. Elucidation of peptide metabolism by on-line immunoaffinity liquid chromatography mass spectrometry. Rapid Commun Mass Spectrom 14 261—269, 2000. 

The major sites of the peptide metabolism are the lungs, followed by the liver and the kidneys. The peptide is degraded by neutral endopeptidase, mast cell tryp-tase and mast cell chymase [17]. 

Figure 8 Proposed catalytic mechanisms for enzymes involved in protein/peptide metabolism using a single bifunctional general acid-base catalyst, (a) CPA and (b) PDF.

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