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A new kinin moiety in human plasma kininogens
T Mindroiu1, O A Carretero, D Proud
1Hypertension Research Division, Henry Ford Hospital, Detroit, MI.
Biochemical and Biophysical Research Communications
|April 29, 1988
Summary
A novel kinin found in human urine was identified as hydroxyproline-containing bradykinin, not the previously suspected alanine variant. This discovery reveals hydroxyproline is present in human kininogens.
Area of Science:
- Biochemistry
- Peptide Research
- Human Physiology
Background:
- A previously isolated urinary kinin was tentatively identified as [Ala3]-Lys-bradykinin.
- Inconsistencies were noted between the natural kinin and its synthetic counterpart, prompting further investigation.
Purpose of the Study:
- To determine if the new kinin originates from human plasma kininogen.
- To elucidate the precise structure of the newly discovered kinin.
Main Methods:
- Incubation of human plasma with human urinary kallikrein.
- Separation of kinins using High-Performance Liquid Chromatography (HPLC).
- Quantification of kinins via Radioimmunoassay (RIA), amino acid sequencing, and composition analysis.
Main Results:
- The new kinin constituted 23% of total kinins released from plasma, with Lys-bradykinin comprising 76%.
- This kinin was also released from purified low- and high-molecular-weight kininogens (40-42% of total).
- Structural analysis confirmed the kinin as [Hyp3]-Lys-bradykinin, containing hydroxyproline, not alanine, at position three.
Conclusions:
- The study identifies [Hyp3]-Lys-bradykinin as a significant kinin derived from human kininogens.
- A substantial portion of human kininogens incorporate hydroxyproline in place of proline at the third position of the bradykinin sequence.