Human Physiology Cell Function and cell Reproduction by Talib F. Abbas

Cell Function and cell Reproduction Virtually everyone knows that the genes, located in the nuclei of all cells of the body, control heredity from parents to children, but most people do not realize that these same genes also control day-today function of all the body’s cells. Each gene, which is a nucleic acid called deoxyribonucleic acid (DNA), automatically controls the formation of another nucleic acid, ribonucleic acid (RNA); this RNA then spreads throughout the cell to control the formation of a specific protein.

NUCLEOSIDES, NUCLEOTIDES, & NUCLEIC ACIDS Nucleosides contain a sugar linked to a nitrogen- containing base. The physiologically important bases, purines and pyrimidines, have ring structures These structures are bound to ribose or 2-deoxyribose to complete the nucleoside. When inorganic phosphate is added to the nucleoside, a nucleotide is formed. Nucleosides and nucleotides form the backbone for RNA and DNA, as well as a variety of coenzymes and regulatory molecules (eg, NAD+, NADP+, and ATP) of physiological importance.

Nucleotide structure

DNA: Deoxyribonucleic acid (DNA) DNA is made up of two extremely long nucleotide chains containing the bases adenine (A), guanine (G), thymine (T), and cytosine (C) . The chains are bound together by hydrogen bonding between the bases, with adenine bonding to thymine and guanine to cytosine. This stable association forms a double-helical structure. The double helical structure of DNA is compacted in the cell by association with histones, and further compacted into chromosomes. A diploid human cell contains 46 chromosomes. A fundamental unit of DNA, or a gene, can be defined as the sequence of DNA nucleotides that contain the information for the production of an ordered amino acid sequence for a single polypeptide chain.

DNA Chromosome DNA segments (exons) separated by segments that are not translated (introns). Near the transcription start site of the gene is a promoter, which is the site at which RNA polymerase

Genetic Code The importance of DNA lies in its ability to control the formation of proteins in the cell. It does this by means of the so-called genetic code. That is, when the two strands of a DNA molecule are split apart, this exposes the purine and pyrimidine bases projecting to the side of each DNA strand. The genetic code consists of successive “triplets” of bases—that is, each three successive bases is a code word. The top strand of DNA, reading from left to right, has the genetic code GGC, AGA, CTT, the triplets being separated from one another by the arrows.

Transcription and translation Because the DNA is located in the nucleus of the cell, yet most of the functions of the cell are carried out in the cytoplasm, there must be some means for the DNA genes of the nucleus to control the chemical reactions of the cytoplasm. This is achieved through the intermediary of another type of nucleic acid, RNA, the formation of which is controlled by the DNA of the nucleus. Thus, the code is transferred to the RNA; this process is called transcription. The RNA, in turn, diffuses from the nucleus through nuclear pores into the cytoplasmic compartment, where it controls protein synthesis , the process of translation.

Control of Gene Function and Biochemical Activity in Cells However, the degree of activation of respective genes must be controlled as well; otherwise, some parts of the cell might overgrow or some chemical reactions might overact until they kill the cell. Each cell has powerful internal feedback control mechanisms that keep the various functional operations of the cell in step with one another.

The “Operon” of the Cell and Its Control of Biochemical Synthesis— Function of the Promoter. Synthesis of a cellular biochemical product usually requires a series of reactions, and each of these reactions is catalyzed by a special protein enzyme. Formation of all the enzymes needed for the synthetic process often is controlled by a sequence of genes located one after the other on the same chromosomal DNA strand. This area of the DNA strand is called an operon, and the genes responsible for forming the respective enzymes are called structural genes.

DNA Replication Replication of the chromosome is accomplished by the two strands splitting apart, and each strand acting as a template for a new DNA strand. Each parental strand thus acts as a template for a new strand running in the opposite direction to create a new chromosome. This replication is said to be semi-conservative. The backbone of each strand consists of Phopho- Ribose part of the nucleic acid being joined to each other by phosphodiester bonds. The phosphate molecule, attached to the 5' carbon ribose atom attaches to the hydroxy molecule at the 3' ribose carbon molecule.

Replication Babbules

Replication Fork Unwinding of parental strands, The formation of the fork is under the control of two enzyme groups, the topoisomerases and the helicases. Lengthening the Transcribed DNA strand, δ-DNA polymerase can only add to an existing chain, it cannot initiate transcription. Initiation is accomplished using a strand of RNA known as RNA primer. This is attached to the parental strand at the initiation point. Two enzymes are involved -  primase and α-DNA polymerase.

Replication legation The lagging strand transcription carried out in the usual manner, away from the replication fork, and continues until it meets the next fragment. Thus the lagging strand is made in fragments - called Okazaki Fragments after scientist who first described them. Okazaki framents are formed by adding a primer strand of RNA catalyzed by the enzymes  primase and α-DNA polymerase. Removing the RNA Primer, When another Okazaki fragment is reached, the RNA primer is removed by δ- DNA polymerase assisted by the enzyme flap endonuclease.

The 3' overhang problem As the replication approaches the end of the chromosome, a problem occurs in the lagging strand. DNA polymerase can only add nucleic acids to the 3' end of the strand, so when the last Okazaki fragment is formed in the lagging, there is no way that than the RNA primer can be reconstituted in the normal manner. When the RNA primer breaks down we are left with an 'overhang' at the 3' end of the parental chain and shortening of the transcribed chain.

Overhang Problem

Telomeres and Chromosome shortening Telomeres are the ends of the eucaryotic chromosome. In humans they consist of numerous (in young humans this can number several thousand bases) repeats of the nucleic acid sequence TTAGGG and its complements. This is the first protection against degradation of the chromosome by overhang. The DNA being shed is merely the non-functional telomere, the TTAGGG sequence. However sooner or later the telomeres will be used up, and the chromosome will start shedding important genes. When this happens, the cell will usually die.

Apoptosis—Programmed Cell Death When cells are no longer needed or become a threat to the organism, they undergo a suicidal programmed cell death, or apoptosis. Necrotic cells may spill their contents, causing inflammation and injury to neighboring cells. Apoptosis, however, is an orderly cell death that results in disassembly and phagocytosis of the cell before any leakage of its contents occurs, and neighboring cells usually remain healthy. Apoptosis is initiated by activation of a family of proteases called caspases.

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