Dipeptidyl peptidase-4: difference between revisions
Diff·revision 4 → 5·15:40, 3 Aug 2024
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| Revision 4 — 22:03, 22 Jul 2024 SatietySunniva (talk) add the reference range with the assay it was established on 2,323 bytes ±0 | Revision 5 — 15:40, 3 Aug 2024 CiteBot (talk) bot: update parent category chain 3,055 bytes +732 | ||
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| 10 | The enzyme exists as a type II membrane protein on endothelial cells, epithelial cells and lymphocytes, and as a catalytically active soluble form in plasma. Cleavage of GLP-1 begins in the capillaries of the intestinal lamina propria, before the hormone reaches the portal vein, so that only a minority of secreted GLP-1 arrives at the systemic circulation intact.{{r|holst2007}} | 10 | The enzyme exists as a type II membrane protein on endothelial cells, epithelial cells and lymphocytes, and as a catalytically active soluble form in plasma. Cleavage of GLP-1 begins in the capillaries of the intestinal lamina propria, before the hormone reaches the portal vein, so that only a minority of secreted GLP-1 arrives at the systemic circulation intact.{{r|holst2007}} |
| 11 | 11 | ||
| + | 12 | DPP-4 defines the design problem for the entire [[GLP-1 receptor agonist]] class, and also constitutes a drug target in its own right. Inhibitors of the enzyme raise endogenous incretin concentrations two- to three-fold and lower glycated haemoglobin by roughly 0.5–0.8 percentage points, an effect substantially smaller than that of receptor agonists because the ceiling is set by physiological secretion.{{r|deacon2019}} | |
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| 12 | == Catalytic action and substrate range == | 14 | == Catalytic action and substrate range == |
| 13 | DPP-4 cleaves the dipeptide His-Ala from the N-terminus of GLP-1(7–36)amide to yield GLP-1(9–36)amide. The truncated product binds the [[GLP-1 receptor]] with roughly two orders of magnitude lower affinity and behaves as a weak antagonist at pharmacological concentrations; whether it has independent cardiovascular activity remains an open question in the literature.{{r|holst2007}} | 15 | DPP-4 cleaves the dipeptide His-Ala from the N-terminus of GLP-1(7–36)amide to yield GLP-1(9–36)amide. The truncated product binds the [[GLP-1 receptor]] with roughly two orders of magnitude lower affinity and behaves as a weak antagonist at pharmacological concentrations; whether it has independent cardiovascular activity remains an open question in the literature.{{r|holst2007}} |
| 14 | 16 | ||
| 15 | The substrate range is wide. Substance P, neuropeptide Y, several chemokines and the incretins are all cleaved, and the enzyme also has non-catalytic functions as a co-stimulatory molecule on T cells and as a binding partner for adenosine deaminase. The breadth of this range is the reason inhibitor development required careful selectivity against the related enzymes DPP-8 and DPP-9.{{r|deacon2019}} | 17 | The substrate range is wide. Substance P, neuropeptide Y, several chemokines and the incretins are all cleaved, and the enzyme also has non-catalytic functions as a co-stimulatory molecule on T cells and as a binding partner for adenosine deaminase. The breadth of this range is the reason inhibitor development required careful selectivity against the related enzymes DPP-8 and DPP-9.{{r|deacon2019}} |
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| + | 19 | Kinetically the enzyme is efficient rather than abundant: plasma DPP-4 activity is sufficient to halve circulating intact GLP-1 in about one minute, which is why the intact fraction must be measured with an assay that distinguishes GLP-1(7–36) from GLP-1(9–36) if the measurement is to mean anything. | |
| 16 | 20 | ||
| 17 | == References == | 21 | == References == |