Studies on the temperature-dependent autoinhibition of human plasma kallikrein I

Levison, Peter R.; Tomalin, Geoffrey

doi:10.1042/bj2050529

Cited by 5 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the time between milk expressions, milk proteins and enzymes exit the mammary epithelial acinar cells and are stored in lactiferous ducts for a sufficient incubation time to allow indigenous proteases to hydrolyze milk proteins. As most of the milk proteases are active at body temperature [17–19], storage of milk within the mammary gland provides favorable conditions for activity of milk proteases. Most milk proteases also function well at the neutral pH of breast milk (including plasmin, kallikrein, thrombin, elastase, carboxypeptidase B2 and cytosol aminopeptidase) [7].…”

Section: Discussionmentioning

confidence: 99%

Milk Proteins Are Predigested Within the Human Mammary Gland

Nielsen

Beverly

Dallas

2017

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

Previous work demonstrates that proteases present in human milk release hundreds of peptides derived from milk proteins. However, the question of whether human milk protein digestion begins within the mammary gland remains incompletely answered. The primary objective of this study was to determine whether proteolytic degradation of human milk proteins into peptides begins within the mammary gland. The secondary objectives were to determine which milk proteases participate in the proteolysis and to predict which released peptides have bioactivity. Lactating mothers (n = 4) expressed their milk directly into a mixture of antiproteases on ice followed by immediate freezing of the milk to limit post-expression protease activity. Samples were analyzed for their peptide profiles via mass spectrometry and database searching. Peptidomics-based protease prediction and bioactivity prediction were each performed with several different approaches. The findings demonstrate that human milk contains more than 1,100 unique peptides derived from milk protein hydrolysis within the mammary gland. These peptides derived from 42 milk proteins and included 306 potential bioactive peptides. Based on the peptidomics data, plasmin was predicted to be the milk protease most active in the hydrolysis of human milk proteins within the mammary gland. Milk proteases actively cleave milk proteins within the mammary gland, initiating the release of functional peptides. Thus, the directly breastfed infant receives partially pre-digested proteins and numerous bioactive peptides.

show abstract

Section: Discussionmentioning

confidence: 99%

Milk Proteins Are Predigested Within the Human Mammary Gland

Nielsen

Beverly

Dallas

2017

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

show abstract

“…Timed aliquots (10 μL) were removed and quenched in 70 μL ice‐cold Quench Buffer I. Following quenching, amidolytic activities were quantified by measuring A 405 at 37°C (to prevent temperature‐dependent auto‐inhibition of PKa). Amidolytic activities were converted to PKa concentrations by reference to a standard curve.…”

Section: Methodsmentioning

confidence: 99%

Polyphosphate, Zn2+ and high molecular weight kininogen modulate individual reactions of the contact pathway of blood clotting

Wang

Ivanov

Smith

et al. 2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background: Inorganic polyphosphate modulates the contact pathway of blood clotting, which is implicated in thrombosis and inflammation. Polyphosphate polymer lengths are highly variable, with shorter polymers (approximately 60–100 phosphates) secreted from human platelets, and longer polymers (up to thousands of phosphates) in microbes. We previously reported that optimal triggering of clotting via the contact pathway requires very long polyphosphates, although the impact of shorter polyphosphate polymers on individual proteolytic reactions of the contact pathway was not interrogated. Objectives and methods: We conducted in vitro measurements of enzyme kinetics to investigate the ability of varying polyphosphate sizes, together with high molecular weight kininogen and Zn2+, to mediate four individual proteolytic reactions of the contact pathway: factor XII autoactivation, factor XII activation by kallikrein, prekallikrein activation by factor XIIa, and prekallikrein autoactivation. Results: The individual contact pathway reactions were differentially dependent on polyphosphate length. Very long-chain polyphosphate was required to support factor XII autoactivation, whereas platelet-size polyphosphate significantly accelerated the activation of factor XII by kallikrein, and the activation of prekallikrein by factor XIIa. Intriguingly, polyphosphate did not support prekallikrein autoactivation. We also report that high molecular weight kininogen was required only when kallikrein was the enzyme (ie, FXII activation by kallikrein), whereas Zn2+ was required only when FXII was the substrate (ie, FXII activation by either kallikrein or FXIIa). Activation of prekallikrein by FXIIa required neither Zn2+ nor high molecular weight kininogen. Conclusions: Platelet polyphosphate and Zn2+ can promote subsets of the reactions of the contact pathway, with implications for a variety of disease states.

show abstract

“…The cofactor was originally distinguished from kallikrein and Factor XIa, but, in retrospect, it might be kallikrein whose activity is modulated by aggregation or autoinhibition. 111 Definite identification, and the relationship of this cofactor with the unidentified Factor XII-dependent plasminogen activator, mentioned previously, has not been achieved as yet. Reinvestigation of the relationship of prekallikrein to the Hageman factordependent plasminogen proactivator originally described by Kaplan and Austen 87 resulted in the conclusion that this proactivator concerned prekallikrein or a derivative as well.…”

Section: Fig 3 Relative Contributions Of Plasma Factors Capable Of mentioning

confidence: 99%