Protein metabolism of the heart.

The heart contains many cell types; mechanical work is done by cardiomyocytes which do not divide but are terminally differentiated and capable of continuous protein synthesis and degradation. The steps in protein synthesis are (1) transport of amino acids into heart cells by a variety of cell-membrane carriers, (2) ATP-dependent activation of the amino acids by specific enzymes, forming aminoacyl-transfer RNA molecules, (3) initiation of protein synthesis on ribosomes to which messenger-RNA molecules are bound at the initiation 'code word', (4) elongation of the polypeptide chains by the repetitive operation of a ribosomal enzyme acting on incoming aminoacyl-transfer RNAs selected by their ability to bind to the messenger-RNA code words in place at any one time, and (5) completion of chain growth when the appropriate termination code word appears in the messenger RNA on the ribosome. Certain genes are available in differentiated heart cells for transcription by RNA polymerase into pre-messenger RNA molecules. These RNA molecules are chemically modified, complexed with proteins and shortened by means of specific excisions before they leave the nuclei as messenger-ribonucleoprotein complexes which can be used for protein synthesis. Regulation of protein synthesis involves both 'quantity' and 'quality' control and is exerted mainly, but not exclusively, at the two levels of initiation, namely that of RNA synthesis in the nucleus, and protein synthesis in the cytoplasm. Protein degradation to the level of amino acids is a process which probably requires disassembly of protein complexes or organelles, and is catalyzed by proteinases present in the cytoplasm or by others occurring in lysosomes, or possibly by both. Basal degradation occurs continuously, and may be supplemented by a separate process, called autophagy, which is under hormonal or nutritional control. The complex processes of biosynthesis and degradation are finely balanced and do not interfere with function despite their occurrence at a rate which means that most of the cardiac protein is replaced every 7 to 14 days. Nutritional and hormonal factors, and especially workload, are determinants that influence the 'set' of the protein turnover mechanism and therefore the size of the organ as a whole.