WJEC Biology for A2: Student Bk

You learned about enzyme inhibitors in the first year of this course. Link Going further Penicillin binds irreversibly to a serine residue at the active site of DD-transpeptidase. It is not complementary to the active site shape and so it is a non-competitive inhibitor. Going further Most amino acids in living organisms have the symmetry described as L-form. The alternative, D-amino acids, are rare in eukaryotes, but occur as a brain neurotransmitter and in some proteins. They are, however, abundant in the peptidoglycan wall of bacteria. Going further Mammalian cells cannot pump tetracycline into their cells. A little may diffuse in but the effect on protein synthesis is negligible. Examtip Make sure you can explain the difference between antibiotics that are: bacteriostatic or bactericidal; broad or narrow spectrum; injected or ingested. Antibiotic mechanisms Penicillin The fungus Penicillium releases penicillin when its growth is inhibited and it is under stress. Penicillin was mass-produced from P. notatum initially, but now, high-yielding strains of P. chrysogenum are used. The fungus is grown aerobically in industrial fermenters and the penicillin is purified for use. The first available penicillin was penicillin G. This had to be injected, rather than ingested, because the stomach acid broke it down. Penicillin V and other derivatives, such as ampicillin, can be taken orally. They work by disrupting the bacterial cell wall: ▪ Penicillin readily diffuses through the cell wall of Gram-positive bacteria and it enters some Gram-negative bacteria through surface molecules called porins. ▪ Bacteria continually make and break down parts of their cell wall. ▪ The enzyme DD-transpeptidase catalyses condensation reactions that make cross- links between amino acid side chains joining peptidoglycan molecules. This enzyme is sometimes called PBP (penicillin binding protein) because penicillin binds to it, acting as an enzyme inhibitor. ▪ The breakdown by hydrolysis continues, so more cell wall is lost than gained. ▪ In addition, as no peptide cross-links are made, precursor molecules build up. These are hydrolysed also. ▪ The cell wall is so weakened that, as water enters the cell by osmosis, the wall is too weak to withstand the increased pressure potential and the cell lyses. Unlike some other antibiotics, such as vancomycin, the penicillin molecule is small enough to penetrate right through the murein, so the whole thickness of the cell wall is affected. Tetracycline The fungus Streptomyces produces tetracycline, a broad-spectrum antibiotic. It acts against Gram-positive and Gram-negative bacteria and so it has a wide medical use against the bacteria that cause acne, against common infections, such as Chlamydia , but also against rare diseases, such as anthrax and plague. It even has some activity against some eukaryote parasites, including Plasmodium . Many bacteria, however, now show some resistance to tetracycline. Tetracycline inhibits protein synthesis. It both diffuses and is pumped into bacteria cells. It binds to the small (30S) subunit of ribosomes and blocks tRNA attachment in the second position, the A site, so no new amino acids can be added to a polypeptide chain. Tetracycline binds reversibly, so its effect is bacteriostatic. Tetracycline mechanism Bacteria growing on agar showing resistance to antibiotics diffusing from filter paper discs 50S 30S tetracycline P site A site Option A: Immunology and disease 269