The cytotoxicity has been associated with either impairment of protein synthesis by the binding of the compounds to the ribosomes of eukaryotic cells, or the dysfunction of cellular membranes.
The structure and function of the ribosome are fascinatinglycomplex. Two-thirds of the ribosome consist of ribosomal RNA (rRNA),while over 50 ribosomal proteins make up the rest. The geneticinformation is delivered to the ribosome by a messenger RNA(mRNA). Transfer RNAs (tRNAs) are adapter molecules, each equipped withan anticodon to match the codons in the mRNA, and charged with an aminoacid that corresponds to the anticodon as dictated by the geneticcode. The ribosome contains three tRNA-binding sites: A, P, and E (seeelongation cycle box, or watch a ). In addition to mRNA and tRNAs, the ribosomeinteracts with protein factors such as the elongation factors Tu (EF-Tu)and G (EF-G), that are important players in the so-called elongationcycle. The elongation cycle results in the addition of an amino acid tothe nascent peptide chain, and consists of three main steps. In thedecoding step, a ternary complex comprised of an aminoacyl-tRNA(aa-tRNA), EF-Tu, and GTP binds to the ribosome,leading to the recognition of the codon by the anticodon. The followingstep is the peptidyl transfer. Here the peptide chain bound to theP-site tRNA is covalently linked to the amino acid bound to the A-sitetRNA. In the translocation step, the position of the mRNA/tRNA complexshifts by one codon, accompanied by a ratchet-like motion of theribosomal subunits.
It facilitatesribosomal binding and therefore, protein synthesis.
The anticodon is complementary to the corresponding mRNA codon and can temporarily match up to it. This is how the tRNA knows when to drop off its amino acid when a protein is being made.
Protein Synthesis Powerpoint Flashcards | Quizlet
Ochratoxin A injected intravenously as a single dose (4.1 mg/kg) in albumin-deficient and normal rats was excreted in the bile and urine 20-70 times faster in the albumin-deficient rats than in normal rats, indicating that the binding of ochratoxin A to blood albumin delays the excretion of the compound through the liver and kidney (Kumagai, 1985).
Ribosomes and Protein Synthesis | Translation (Biology) …
The competitive inhibitor effect of ochratoxin A on tRNA synthetase and protein synthesis in rat hepatoma cells can be prevented by the addition of phenylalanine in the cell culture medium at a molar ratio of phenylalanine: ochratoxin A of 1.7:1 (Creppy et al., 1979b).
transfers amino acids to ribosomes during protein synthesis
In terms of clinical haematological changes, such as haemorrhaging, blood cell counts, serum-enzyme activities, and serum-protein levels, the no-observed-effect level could not be accurately determined, but was higher than 12 mg/kg, based on the weight gain.
Role of Ribosomes in Protein Synthesis (With Diagram)
Factor X, and prothrombin and fibrinogen activities were reduced only at the highest dietary dose, whereas Factor VII was reduced at dietary doses of 4, 8, and 16 mg/kg and was the most sensitive of the clotting components to T-2 toxin toxicosis.
Ribosomes provide framework on which protein synthesis takes place
Much of what is known about SecM stalling comes from biochemicalexperiments, in which every amino acid in SecM's sequence has beenmutated and the resulting effects measured. These experiments revealedfew residues as critical, although one stands out in every species asinvariable: arginine 163 (R163, see Fig. 13 below). However, untilrecently, little was known about the precise mechanisms at work. Acryo-EM map of a SecM-stalled ribosome revealed a shifted linkage in thePTC between the P-site tRNA and the SecM peptide. Although the shift wasonly 0.2 nm, it was hypothesized to be sufficient to inhibit peptide-bondformation, preventing synthesis of the remainder of SecM.