Prokaryotic and eukaryotic cells compared

Mitochondria and chloroplasts did not arise inside the eukaryotic cell; they were once free-living prokaryotes that were engulfed and kept. The evidence is unusually direct, and it is the strongest reason to say that eukaryotes descended from prokaryotes rather than appearing beside them. Both organelles are about the size of a bacterium. Both are wrapped in a double membrane, and the inner membrane carries the chemical signature of a bacterial membrane while the outer one matches the host vesicle that swallowed it. Both contain their own DNA, which is circular, not packaged as linear chromosomes, and inherited separately from the nuclear genome. Both build their proteins on ribosomes of bacterial lineage rather than the 80S type of the surrounding cytoplasm — 70S in chloroplasts, but a reduced particle of about 55S in the mitochondria of mammals — and both divide on their own by binary fission rather than by mitosis. In the 1960s Lynn Margulis assembled these observations into the endosymbiotic theory, and gene sequencing later placed mitochondrial genes inside the alphaproteobacteria and chloroplast genes inside the cyanobacteria — the very blue-green algae named in the notes, now correctly recognised as prokaryotes. In humans the mitochondrial genome is a small circle of about 16,569 base pairs carrying thirty-seven genes, thirteen of which encode proteins of the respiratory chain; it is inherited almost exclusively from the mother, which is why mitochondrial disease follows a maternal pattern in families and why genetic counselling for it differs from counselling for a mutation in a nuclear gene. The same bacterial ancestry explains a clinical trap: drugs aimed at bacterial 70S ribosomes can also disturb mitochondrial protein synthesis, which contributes to the hearing loss and kidney injury associated with aminoglycosides and to the bone marrow suppression of chloramphenicol.

The S in 70S and 80S is a Svedberg unit, and it measures how fast a particle sediments in a centrifuge rather than how heavy it is, which is why the numbers do not add: a bacterial ribosome is 70S but is built from a large 50S part and a small 30S part, while a human cytoplasmic ribosome is 80S but built from 60S and 40S parts. The pharmacological importance is that the two machines have different shapes, so a drug can be designed that jams the bacterial one and leaves the human one working. This is selective toxicity, the principle Paul Ehrlich called the magic bullet: the drug must hit a target that the pathogen has and the patient’s cells do not. Aminoglycosides such as gentamicin and streptomycin bind the small bacterial part and make it misread messenger RNA, so the bacterium inserts wrong amino acids and its proteins become useless. Tetracyclines block that same small part and stop the message from being read at all. Macrolides such as erythromycin and azithromycin, chloramphenicol and linezolid act on the large bacterial part, blocking the formation of the peptide bond or the movement of the ribosome along the message. Human cytoplasmic ribosomes are 80S and are not affected at the doses used, which is why these drugs can be given systemically. The selectivity is not perfect, and the reason is mitochondrial ancestry: mitochondria carry ribosomes of bacterial lineage rather than 80S particles, so the same drugs can interfere with the patient’s own energy production. That is the mechanism behind the dose-limiting ototoxicity and nephrotoxicity of aminoglycosides, the rare aplastic anaemia of chloramphenicol, and the lactic acidosis and marrow suppression seen with prolonged linezolid, as well as the diarrhoea caused by disturbance of the gut flora. It also explains why ribosome-targeting drugs cannot be used against fungi: fungal ribosomes are 80S like our own, so an antifungal must attack something else, such as the ergosterol of the fungal membrane or the glucan of the fungal wall, which is one reason antifungal therapy is slower, narrower and more toxic. For nursing, the practical consequences are therapeutic drug monitoring for gentamicin, baseline and repeated checks of renal function and hearing, and never assuming that “it only affects bacteria” means “it cannot affect the patient”.

The words the notes use — lower Protists and higher Protists — belong to an older picture in which living things were arranged on a single ladder from simple to complex. Modern classification is not a ladder but a branching tree, and the prokaryote–eukaryote line is the deepest branch that cell structure alone can draw: it was Roger Stanier and C. B. van Niel who made that structural distinction central in 1962, and the notes’ date of 1992 is wrong. Later systems kept the boundary but changed what sits on either side. Whittaker’s five-kingdom scheme of 1969 placed all prokaryotes in a single kingdom, Monera, beside Protista, Fungi, Plantae and Animalia. That scheme broke when Carl Woese and his colleagues compared the sequences of 16S ribosomal RNA, a molecule that every cell needs and that changes slowly enough to record ancient relationships. The comparison showed that the organisms then called archaebacteria differ from ordinary bacteria as much as both differ from eukaryotes, so in 1990 the three-domain system was adopted: Bacteria, Archaea and Eukarya. Archaea are prokaryotes in cell plan — no nucleus, one circular chromosome, 70S ribosomes — but they are chemically distinct: their membrane lipids are joined by ether bonds rather than ester bonds, their RNA polymerase resembles the eukaryotic enzyme, and their walls, where present, are not true peptidoglycan. The group includes the methanogens of the gut and of sewage, the extreme halophiles of salt lakes and the thermophiles of hot springs. No archaeon is a recognised human pathogen, which is why the clinically useful contrast remains the one this section teaches: a prokaryotic cell presents targets that a eukaryotic cell does not. The lesson of the redrawing is that names follow evidence. The notes call blue-green algae prokaryotes, which is correct, but the name is a fossil: they are cyanobacteria, and calling them algae hides the fact that they are bacteria that photosynthesise. For a nurse, the translation never changes: identify the cell type, and you know which drug family can possibly work.