Alfred Bennun, Ph.D.
Full Professor-Emeritus-Rutgers University Consultant,
Rutgers University, NJ, USA
Series: Biochemistry and Molecular Biology in the Post Genomic Era
Sensorial neurons activate the locus coeruleus long axons for a presynaptic Ca2+-dependent release of noradrenaline (NA). Postsynaptic adenylyl cyclase (AC) of several areas of the brain shows Mg2+-dependent responsiveness to the neurotransmitter in the absence of Ca2+ when the free Mg2+ is present in excess of substrate Mg-ATP.
The brain capillary glucose uptake by red-cells leads to the endogenous generation of 2,3-DPG, and promotes the oxyHb-deoxygenation to discharge Mg2+ at the noradrenergic synapses.
Since adrenaline cannot cross the blood brain barrier, it could not have a feedback; however, cortisol does.
cAMP controls the activation of the initial voltage-gated state of the action potential, configuring nerve impulse, transcription-plasticity mechanism and long-term memory.
Overall, this molecular mechanism could be used to propose a model linking environmental stimulus resulting in cAMP and the rate of gene expression.
DNA-dependent RNA polymerase activation is inducible, expressed under the conditions of adaptive value by cAMP. The zipper-closure role of the enzyme functions with divalent metal for inclusion of the cyclic nucleotide cAMP and cGMP in DNA. cAMP by binding to Mg2+ ion interacts with the negatively charged phosphate groups. The latter chelated by Mg2+ opens the double chain in DNA for binding DNA-dependent RNA polymerase. The greater activity of cAMP-Me2+-DNA complex with regard to a stabilized double helix allows for the introduction of a mechanism for genetic induction vs constitutive state.
The cAMP-Me2+-DNA complex by increasing a turn-on activity could consolidate cAMP stimulus, allowing genetic variance by insertion of cAMP, by adhesion of cAMP to stimulate a similar area of the DNA at different stages on the overall evolutionary/adaptive response to environmental stress.
Charles Darwin discovers evolution relating the adaptive strength of the birds’ beaks conditioned by the hardness of environmental nuts.
The nutritional stress increases free Mg2+. Noradrenaline-stimulated adenylyl cyclase stimulates the hypothalamus, which involves additional metabolic resources to increase the strength of the bird beak. Specific stimulus for the DNA location controlling the bird’s beak development allows for a complementary configuration for cAMP insertion into the near specific bird-beak-DNA segment involved in beak growing and development. cAMP-Me2+-DNA complex inserted in the DNA complex is continuously open for DNA transcript involved in developing a new, stronger beak.
A genetic link between the induction mechanism and a transitory modification of DNA expression could enrich the relationship of induced vs constitutive templates in the reproductive cells.
The balance would favor the tendency toinduce activation and increase the DNA response to external stimuli over the constitutive remaining and more stable DNA. (Imprint: Nova)