Ricin kinetics

The metabolism and elimination of toxalbumins is poorly understood. Ricin is eliminated by first order kinetics when injected IV into mice and human cancer patients (Godal et al, 1984). The plasma half-life in humans is about 2 days (Kopferschmitt, 1983). 

The glycoproteins (ricin) are poorly absorbed from the gastrointestinal tract however, once absorbed, they most likely follow a distribution pattern similar to that of albumin. Many cell surfaces contain receptors specific for the ricin molecules. This molecule consists of two subunits, A and B, bound by a disulfide link. When this link is broken, the B subunit binds to galactose-containing receptors in the cell wall and is transported intracellularly. The A subunit inhibits protein synthesis. The liver, spleen, adrenal cortex, and bone marrow are the primary sites of distribution. The biotransformation and elimination of toxalbumins are poorly understood. The elimination half-life in one patient was 2 days. The reported disappearance of ricin from the plasma is according to first-order kinetics when... 

Cancer patients treated with i.v. ricin every 2 weeks at doses as low as 14 pg/m" (about 0.5 pg/kg) experience flu-like symptoms of fatigue and myalgia with occasional episodes of nausea or emesis most patients tolerate doses up to 18-20 pg/m" (Fodstad et al., 1984). Ricin is cleared from circulation within 24 h after a bolus injection, with apparently first-order kinetics and 99% clearance by 18 h (Fodstad et al., 1984). 

Chen, X.Y., Link, T.M. and Schramm, V.L. (1998) Ricin A-chain kinetics, mechanism, and RNA stem-loop inhibitors. Biochemistry, 37, 11605-11613. 

Sandvig, K., Olsnes, S. and Pihl, A. (1976) Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J Biol Chem, 251, 3977-3984. 

Chaddock JA and Roberts LM (1993). Mutagenesis and kinetic analysis of the active site Glul77 of ricin A-chain. Protein Eng, 6, 425 431. 

Kinetic experiments have shown that pure ricin A chain inactivates salt-washed ribosomes at a rate of 1500 ribosomes per min per A chain molecule. The Km with respect to ribosomes is (1-2) x 10 7 M, which indicates that the A chain acts in the cytosol at close to its Fmax. Penetration of a single A-chain molecule into the cytoplasm is believed to be sufficient to kill a cell [53]. Ricin inhibits protein synthesis by both animal and plant ribosomes, including those from Ricinus communis itself [116], but, in general, plant ribosomes seem to be significantly less sensitive. 

Youle R, Neville D. Kinetics of protein synthesis inactivation by ricin-anti-thy.1.1 monoclonal antibody hybrids Role of the ricin B subunit demonstrated by reconstitution. J Biol Chem. 1982 267 1598-1601. 

Chen X-Y, Berti PJ, Schramm VL (2000) Ricin a-chain kinetic isotope effects and transition state structure with stem-loop RNA f- J Am Chem Soc 122 1609-1617. doi 10.1021/ Ja992750i... 

Sturm, M.B., Schramm, V.L., 2009. Detecting ricin sensitive luminescent assay for ricin A-chain ribosome depurination kinetics. Anal. Chem. 81, 2847-2853. 

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