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tRNA is a key component in translation. The various tRNA species decode at different speeds and fidelity that depend on the availability of the tRNA species, of the codon choice, and of the codon context. Some tRNA may act as a cofactor in enzymatic reactions. The first precursor to porphyrins in many bacteria and organelles is glutamate-1-semialdehyde (GSA), which is formed after the ligation of Glu to tRNA^Glu. In bacteria, an unexpected link between tRNA modification and intermediary metabolism is the requirement of chorismic acid or its derivative in a previously unknown metabolic pathway to synthesize uridine-5-oxyacetic acid (cmo⁵U34) and its methyl ester (mcmo⁵U34). Thus, whereas links between tRNA modification and metabolism are well documented in bacteria, such links also exist in eukaryotes. In a study of human immunodeficiency virus (HIV)-positive intravenous heroin addicts, researchers found that serum Ψ was an independent predictor of progression to AIDS in Centers for Disease Control and Prevention (CDC) stage A2 HIV-infected patients. Interestingly, queuine in higher organisms may have such a role, since it influences the physiology of the cell in a tRNA independent way. In multicellular organisms, there is turnover of stable RNA, and modified nucleosides are found intact in rather large amounts in serum and in the urine. Therefore, urinary excretion of modified nucleosides reflects the turnover of RNA. Most of the RNA, which contains modified nucleosides in the multicellular eukaryotes, is stable and participates in translation (rRNA and tRNA) or in splicing (the various U RNAs).