Molecular genetics protein synthesis

Gonsiderable new material has been added on RNA synthesis, protein synthesis, gene regulation, and various aspects of molecular genetics. 

What are the facts of life One of the most striking is that all known living systems involve the same types of polymers, i.e., three varieties of homochiral biopolymers. That is, each variety is composed of unique molecular building blocks having the same three-dimensional handedness. Thus, with rare exceptions, the proteins found in cells are composed exclusively of the 1-enantiomers of 19 optically active amino acids (Fig. 11.1). Similarly, only D-ribose and 2-deoxy-D-ribose sugars are found in the nucleic acid polymers that make up the RNAs and DNAs, which are essential for protein synthesis in the cell and for the transmission of genetic information from one generation to the next. 

In recent years the psychopharmacologist has paid increasing attention to the examination of brain proteins with which psychotropic drugs react, and also the molecular mechanisms that control the synthesis and cellular function of these proteins. For this reason, any understanding of psychopharmacology requires some knowledge of the basic techniques of molecular genetics. 

Some time after the evolution of this primitive protein-synthesizing system, there was a further development DNA molecules with sequences complementary to the self-replicating RNA molecules took over the function of conserving the genetic information, and RNA molecules evolved to play roles in protein synthesis. (We explain in Chapter 8 why DNA is a more stable molecule than RNA and thus a better repository of inheritable information.) Proteins proved to be versatile catalysts and, over time, took over that function. Lipidlike compounds in the primordial soup formed relatively impermeable layers around self-replicating collections of molecules. The concentration of proteins and nucleic acids within these lipid enclosures favored the molecular interactions required in self-replication. 

The molecular and genetic relationship between enzyme induction and repression was clarified by the genetic research of Jacob and Monod at the Pasteur Institute, Paris (see reference l7>). Their classic work led them to develop the operon hypothesis for the control of protein synthesis in prokaryotes, which has since been verified by direct biochemical experiments. 

Extremely sophisticated biological machinery based on specific non-covalent molecular recognition is involved in biological processes such as DNA replication, the transcription of the genetic code and in RNA mediated protein synthesis at the ribosome. This biochemical molecular machinery has recognisable mechanical features. 

The most dramatic advances, without doubt, have been in protein biochemistry. The genetic basis of lipoprotein disorders is being probed with the tools of molecular biology, proteins concerned with lipoprotein metabolism are being characterized with structural and physiological studies, lipoprotein receptors are being fully characterized, and competitive inhibitors of the rate-limiting enzyme for cholesterol synthesis, HMG-CoA reductase, have been produced. 

In mammalian cells, some 1% of the total cellular DNA is found in the mitochondria. This DNA is double stranded, circular, and small, with a molecular weight of about 10 million, which is in the same range as that of viral DNAs. Some four to ten molecules of DNA per mitochondrion, along with some ribosomes, are found in the matrix space. DNA replication, transcription, and synthesis of some mitochondrial proteins take place in the matrix space. This protein synthesis very much resembles that of bacteria. The mitochondrial genetic code differs from the "universal" genetic code (Chapter 12) used for nuclearly encoded proteins and bacteria. The reasons for this are unknown. 

Both pro- and eukaryotic cells have three types of RNA. The largest is messenger RNA (mRNA), whose molecular weight can be as high as 106. It carries genetic information from DNA to the protein synthesis machinery. It is a product of DNA transcription, and it is translated (expressed) into a protein via... 

The central dogma of molecular biology describes how one form of biological information (an organism s genetic sequence) is processed in terms of DNA replication, RNA transcription, and protein synthesis. However, a related mystery is yet to be worked out in sufficient detail how is the information encoded in the DNA (i.e., genotypes) related to cellular functions (i.e., phenotypes) How do different signals tell different cells to synthesize different proteins ... 

Studies of the mineralization of the larvae of sea urchins (they can be conveniently grown in synchronous culture) have made it possible to utilize molecular biologic techniques to determine gene expression, protein synthesis, and macro-molecular organization as well as the sequences of mineral deposition (Benson et al., 1987). These are some of the earliest forms to be studied and illustrate the connections between genetics and biomineralization. Stem cells responsible for spicule formation can be isolated and produce normal spicules in vitro (Kitajima and Okazaki, 1980) since spines regenerate the secondary mineralization process can also be studied (Ebert, 1967). 

Information most probably entered nascent life with the appearance of RNA. One need only look at Figure 10.1 to realize that DNA can be dispensed with provided that RNA can be replicated. In such a DNA-free RNA world," RNA would have served both as the repository of genetic information and as the agent of the expression of this information, hrst by itself and later by way of its protein translation products. On the other hand, the key functions carried out by RNA molecules in protein synthesis indicate strongly that proteins - defined as special polypeptides made with a distinct set of twenty amino acids - are an invention of RNA. It has been proposed, because of the molecular complexity of RNA, that this substance may itself have been preceded by some simpler information-bearing molecule. This hypothesis, however, is unsupported by any evidence. 

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