regulation

Regulation is key to cellular differentiation, to control of gene expression, and to control of cellular metabolic processes. Gene regulation is key to biological evolution because alterations in regulatory genes can amplify small alterations in genotype into large alterations of phenotype.

Tables  Regulatory Proteins Sequences  gene regulation in E.coli :

1. Cellular differentiation – within the cell cycle, DNA replication and cell division are coordinated such that the distribution of new DNA copies to each daughter cell is ensured. Cell cycle entry and progression is regulated by checkpoints and by a series of CDC gene encoded cyclin-CDKs. Differentiation into distinct tissue types in multicellular organisms requires regulated timing of the location and expression of specific genes, such that initially totipotent (all lines - zygotes, early embryonic cells), and subsequently pluripotent (many lines – stem, meristematic) cells become committed to the characteristics of single cell lines. Differentiation involves alterations in numerous aspects of cell physiology such that structure and polarity are determined, while metabolic activity, responsiveness to signals, and gene expression are variably regulated.

2. Regulation of gene expression :
Prokaryotes:
(a) long-term regulation of metabolism in bacteria is achieved through the control of initiation of transcription by such mechanisms as sigma factors, repressor proteins during induction and repression, and by the attenuation of many biosynthetic operons.

Control of prokaryotic gene expression is brought about by control of the rate of transcriptional initiation by two DNA promoter sequence elements that promote recognition of transcriptional start sites by RNA polymerase. Regulatory accessory proteins alter the activity of RNA polymerase at a given promoter by affecting the ability of RNA polymerase to recognize start-sites. These regulatory proteins can act both positively (activators) and negatively (repressors). Proteins with sequences termed operators regulate the accessibility of promoter regions to prokaryotic DNA. The operator region is adjacent to the promoter elements in most operons, and in most cases the sequences of the operator bind a repressor protein. However, E. coli possesses several operons that contain overlapping sequence elements, one that binds a repressor and one that binds an activator.

Two major modes of transcriptional regulation in bacteria (E. coli) utilize repressor proteins to control the expression of operons.
1. Catabolite-regulated operons employ repressor proteins to down-regulate operons that produce gene products necessary for the utilization of energy. A classic example of a catabolite-regulated operon is the lac operon, responsible for obtaining energy from b-galactosides such as lactose.
2. Attenuated operons regulate operons that produce gene products necessary for the synthesis of small biomolecules such as amino acids. Expression of the an attenuated operon class of operons is repressed by sequences within the transcribed RNA. A classic example of an attenuated operon is the trp operon, responsible for the biosynthesis of tryptophan.  Table gene regulation in E.coli .

In eukaryotes, mechanisms for control of gene expression are more varied than in prokaryotes
(a) Most commonly affect the rate of transcription is regulated,
(b) Some mechanisms alter the rate of RNA processing within the nucleus.
(c) Alternative promoters can modify the location at which transcription commences, altering the protein transcribed from a particular DNA sequence.
(c) Some control mechanisms affect the stability and degradation of RNA molecules (nonsense-mediated decay, nonstop decay).
(d) Some regulatory mechanisms control the efficiency of ribosomal translation into ribosomal polypeptides and proteins.
(e) Much variability in the proteome is provided by alternative splicing, which generates different proteins from the same genome.
(f) Epigenetic mechanisms modify mRNAs.

Table  Regulatory Proteins Sequences  Comparisons of Eubacteria, Archaea, and Eukaryotes  Gene Regulation in E.coli .

3. Regulation of metabolism primarily involves modulation of key steps that determine the flux of metabolites through various pathways. Metabolism is regulated such that (a) cell components are maintained at the proper concentrations, despite alterations in the environmental milieu, and such that (b) energy and materials are conserved.

Localization of enzymes and metabolites in separate compartments of a cell assists in regulation and coordination of metabolic activity. The activity of a metabolic pathway is often controlled by the end-products of the pathway (a)through feedback inhibition of regulatory enzymes located at the start of the sequence, or (b) at branch points.

Enzymes control the flux of metabolites through metabolic pathways, regulating the rates of metabolic pathways, and mechanisms exist to control the activity or synthesis of allosteric and inducible/repressible enzymes. The activity of regulatory enzymes can be altered through reversible binding of effectors to a regulatory (allosteric) site that is separate from the catalytic site, or through covalent modification of the enzyme. Regulation of enzyme activity operates rapidly and serves as a fine-tuning mechanism to adjust metabolism from moment to moment.

 Glycolysis in bacteria  Comparison of Photosynthesis and Respiration  Enzymes Function Krebs Cycle  Enzymes Cofactors of Krebs Cycle  Second Messengers  Phosphate-handling Enzymes  Electron Transport Chain vs Oxidative Phosphorylation  Regulatory Proteins Sequences  Gene Regulation in E.coli  Cell signaling  Second Messengers .

· adenylyl (adenylate) cyclase · calcium ions · cAMP-dependent protein kinase · CDKs · cyclin-dependent kinases · DAG · diacylglycerol · DNA ligases · ERKs· GPCRs · GPCR families · guanylate cyclases · guanyl cyclase · inositol triphosphate · IP3 · MAP kinases · mitogen activated protein kinases · phosphatases · phosphodiesterases · phospolipases · phosphorylation · PKA · PKC · phospholipase C-gamma · protein kinase A · protein kinase C · protein tyrosine kinases (PTKs) · receptor tyrosine kinases · second messengers · second messenger cAMP · second messenger cGMP · signal transduction · two-component systems ·

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