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Posts Tagged ‘synaptic function’


Larry H. Bernstein, MD, FCAP, Interviewer, Curator

Leaders in Pharmaceutical Intelligence

Biochemical Insights of Dr. Jose Eduardo de Salles Roselino

https://pharmaceuticalintelligence.com/12/24/2014/larryhbern/Biochemical_
Insights_of_Dr._Jose_Eduardo_de_Salles_Roselino/

Biochemical Insights of Dr. Jose Eduardo de Salles Roselino

How is it that developments late in the 20th century diverted the attention of
biological processes from a dynamic construct involving interacting chemical
reactions under rapidly changing external conditions effecting tissues and cell
function to a rigid construct that is determined unilaterally by the genome
construct, diverting attention from mechanisms essential for seeing the complete
cellular construct?

Larry, I assume that in case you read the article titled Neo – Darwinism, The
Modern Synthesis and Selfish Genes that bares no relationship with Physiology
with Molecular Biology J. Physiol 2011; 589(5): 1007-11 by Denis Noble, you might
find that it was the key factor required in order to understand the dislodgment
of physiology as a foundation of medical reasoning. In the near unilateral emphasis
of genomic activity as a determinant of cellular activity all of the required general
support for the understanding of my reasoning. The DNA to protein link goes
from triplet sequence to amino acid sequence. That is the realm of genetics.
Further, protein conformation, activity and function requires that environmental
and micro-environmental factors should be considered (Biochemistry). If that
were not the case, we have no way to bridge the gap between the genetic
code and the evolution of cells, tissues, organs, and organisms.

  • Consider this example of hormonal function. I would like to stress in
    the cAMP dependent hormonal response, the transfer of information
    that 
    occurs through conformation changes after protein interactions.
    This mechanism therefore, requires that proteins must not have their
    conformation determined by sequence alone.
    Regulatory protein conformation is determined by its sequence plus
    the interaction it has in its micro-environment. For instance, if your
    scheme takes into account what happens inside the membrane and
    that occurs before cAMP, then production is increased by hormone
    action. A dynamic scheme  will show an effect initially, over hormone
    receptor (hormone binding causing change in its conformation) followed
    by GTPase change in conformation caused by receptor interaction and
    finally, Adenylate cyclase change in conformation and in activity after
    GTPase protein binding in a complex system that is dependent on self-
    assembly and also, on changes in their conformation in response to
    hormonal signals (see R. A Kahn and A. G Gilman 1984 J. Biol. Chem.
    v. 259,n 10 pp6235-6240. In this case, trimeric or dimeric G does not
    matter). Furthermore, after the step of cAMP increased production we
    also can see changes in protein conformation.  The effect of increased
    cAMP levels over (inhibitor protein and protein kinase protein complex)
    also is an effect upon protein conformation. Increased cAMP levels led
    to the separation of inhibitor protein (R ) from cAMP dependent protein
    kinase (C ) causing removal of the inhibitor R and the increase in C activity.
    R stands for regulatory subunit and C for catalytic subunit of the protein
    complex.
  • This cAMP effect over the quaternary structure of the enzyme complex
    (C protein kinase + R the inhibitor) may be better understood as an
    environmental information producing an effect in opposition to
    what may be considered as a tendency  towards a conformation
    “determined” by the genetic code. This “ideal” conformation
    “determined” by the genome  would be only seen in crystalline
    protein.
     In carbohydrate metabolism in the liver the hormonal signal
    causes a biochemical regulatory response that preserves homeostatic
    levels of glucose (one function) and in the muscle, it is a biochemical
    regulatory response that preserves intracellular levels of ATP (another
    function).
  • Therefore, sequence alone does not explain conformation, activity
    and function of regulatory proteins
    .  If this important regulatory
    mechanism was  not ignored, the work of  S. Prusiner (Prion diseases
    and the BSE crisis Stanley B. Prusiner 1997 Science; 278: 245 – 251,
    10  October) would be easily understood.  We would be accustomed
    to reason about changes in protein conformation caused by protein
    interaction with other proteins, lipids, small molecules and even ions.
  • In case this wrong biochemical reasoning is used in microorganisms.
    Still it is wrong but, it will cause a minor error most of the time, since
    we may reduce almost all activity of microorganism´s proteins to a
    single function – The production of another microorganism. However,
    even microorganisms respond differently to their micro-environment
    despite a single genome (See M. Rouxii dimorphic fungus works,
    later). The reason for the reasoning error is, proteins are proteins
    and DNA are DNA quite different in chemical terms. Proteins must
    change their conformation to allow for fast regulatory responses and
    DNA must preserve its sequence to allow for genetic inheritance.
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English: diagram based on Squire and Zola (199...

English: diagram based on Squire and Zola (1996) about decalarative and non-declarative memory (Photo credit: Wikipedia)

Larry H Bernstein, MD, FCAP, Reporter

An interesting paper recently published.

I only show abstract and part of introduction.

Available online http://www.interesjournals.org/JMMS

Copyright © 2012 International Research Journals
Review

Martin Ezeani, Maxwell Omabe, J.C. Onyeanusi, I.N. Nnatuanya, Elom S.O.
*1Department of Neurosciences, University of Sussex UK
*2Molecular Pathology Division, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Ebonyi State
University.
*3Department of Medical Biochemistry, Faculty of Basic Medical Sciences, Ebonyi State University.

ABSTRACT
Molecular studies of both declarative and non-declarative memory in Aplysia californica, lymaea stagnalis and hippocampal slices implicate experience-dependent changes of synaptic structure and strength as the fundamental basis of memory storage and maintenance. The essential outcome of these changes in synaptic structure and strength is our ability to remember what we are thought.
Remembrance is of critical importance. In disease conditions like Alzheimer’s there is lack of the ability to recreate the past. From this perspective, memory literally is the glue that binds our mental life, the scaffolding that holds our personal history and that makes it possible to change throughout life. What causes memory persistence after labile phase of memory is not yet fully known.

Elegant discoveries have explained why labile memory phase could persist over time into long term memory phase. Synaptic connections are not fixed but become modified by learning. These modifications in synaptic structure and strength persist and become the fundamental component of memory storage
after learning. Learning-induced changes in behavioural performance are the result of a fundamental physiological phenomenon.

The fundamental physiological phenomenon is neuronal plasticity. In the
process of neuronal plasticity, we review only the emerging aspect of the roles of prion like-protein, neuronal astrocyte and protein kinase Mzeta (PKMζ) in memory maintenance.
Keywords: Memory Maintenance, NMDARs and AMPARs, CPEB, Neuronal Lacate and Protein Kinase Mzeta.

INTRODUCTION
Memory defines the ability to retain, store and recall events. Memory maintenance is the process of keeping optimally these events. For instance, the beautiful nature of Sussex genomic center and its Medical School are
examples of explicit or declarative memory. Memories such as these are stored very well in the brain for recall of details later in life. Apart from these explicit or
declarative memories another type of memory is implicit or non-declarative memory. In this latter type of memory, motor skills and other type of tasks are done through performance with no conscious recall of past experience.
For instance riding a bicycle and driving a car.

Studies suggest that experience-dependent changes of synaptic strength, growth, structure and fundamental mechanism are ways of which these memories are encoded, processed and stored within the brain (Hawkins et al.,
2006; Bailey et al., 2004; and Beckinschtein et al., 2010). In these processes of initial memory formation and consolidation, memory basically exists in forms. These forms may include; short term memory (STM), intermediate memory (IM) and Long term memory (LTM) (Beckinschtein et al., 2010). There is also early and late LTM. Memories are maintained because, if all these memories are formed by similar molecular process, then what accounts for these types of basic memory?

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