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Mg Atp
1. Role of Ion Mg as Cofactor ATP in Assurance
of Energetic Environment Cells
Aurelian
Udristioiu,
Clinical Laboratory, Medical Analyses
Emergency County Hospital Targu Jiu
2. Magnesium is an essential element in biological systems.
Magnesium occurs typically as the Mg2+ ion. It is an essential
mineral nutrient for life and is present in every cell type in every
organism. For example, ATP (adenosine triphosphate), the main
source of energy in cells, must be bound to a magnesium ion in
order to be biologically active. What is called ATP is often
actually Mg-ATP.
Mg to Cell membranes
Biological cell membranes and cell walls are poly-
anionic surfaces. This has important implications for the
transport of ions, particularly because it has been shown
that different membranes preferentially bind different ions.
Both Mg2+ and Ca2+ regularly stabilize membranes by
the cross-linking of carboxylated and phosphorylated
head groups of lipids.
3. The transport of ions is dependent on both the concentration gradient
of the ion and the electric potential (ΔΨ) across the membrane, which
will be affected by the charge on the membrane surface. The entry of
Mg2+ into cells may occur through one of two pathways, via channels
using the ΔΨ (negative inside) across this membrane or by support
with H+ ions.
A schematic of a plant cell is shown including the four major
compartments currently recognition as interacting with Mg2+, H+-
ATPases maintains a constant ΔpH across the plasma membrane
and the vacuole membrane. Mg2+ is transported into the vacuole
using the energy of ΔpH. The transport of Mg2+ into mitochondria
probably uses ΔΨ and it is likely with chloroplasts which take Mg2+
by a similar system.
Magnesium ions can be critical in maintaining the positional integrity
of closely clustered phosphate groups.
These clusters appear in numerous and distinct parts of the
cell nucleus and cytoplasm.
Figure 1
5. Mg and ANAEROBIC METABOLISM in CYTOPLASM OF CELLS
In all alive bodies immediated energy sources there are process of
oxidation of glucose. In biochemical processes of Anaerobic.
Metabolism, the donor of phosphate group is ATP and the reaction is
catalyzed of the enzymes hexokinase or glucokinase.
hexokinase
Glucose +ATP=Glucose-6-phosphate
Mg
(DGo = -3.4kal/mol).
The process of transformation of glucose-6-phosphate in fructose-6-
phosphate is catalyzed by enzyme phospho-glucomutase, having as
and co-factor ATP+Mg.
In fellow step,transformation G-6-phosphate in F-1-6-biphophate, under the
action of enzyme phosphofructokinase, reactant is ATP-Mg, and the reaction
have place with decrease of free energy, being un-reversible in cellular normal
conditions in sequence of glicolitc degradation.
6. In twice steady of glicolyse, the acid phopho-enolpiruvic, in present of
Mg²+ and K+ is transformed in piruvic acid. In cancer cells or in absence
of oxygen have place the transformation piruvic acid in lactic acid and the
glicolyse stop here.
The energetic sum of anaerobic-glicolyse is total DG0 = -34.64
kcal/mol but the molecule of glucose contain 686 kcal/mol and the
difference (-654 .51 kcal ) can remains a potential for un-controlled
reactions in carcinogenesis.
Lack of Mg in one of reaction of anaerobic glicolyse, can block the
transformation of anaerobic process in aerobic process and the
carcinogenetic process will be installed on via pentozo-phosphate
away( G-6-P + NADPH+ - RIBOZA – 5 –P + CO2 + NAPHH+
2H+).
The pentose way is a strategic steps for malign cell with multiple
syntheses of nucleic acids, without ATP consume, in build of
purine bases necessary in build of sequences of AND.
7. CITOPLASM CELLS-AEROBIC METABOLISM
In Aerobic Glucose Metabolism, acid citric oxidation is helped of ADP
and Mg²+ increases speed of reaction: Iso-citric acid + NADP (NAD)
---isocitrat-dehidrogenase = alpha-ceto-glutaric acid. Finally, in a
health cell, will be delivery -299.06 kcal(71.54 KJ), minim level of
energy for alive cells being 60 KJ, corresponding to a potential
membrane of +- 60-90 mEv, the difference from 654.51 kcal will be
lost by reversible reactions.
Role of ATP-Mg to Mitocondryal Level
To level of mitochondria the gradient of pH and potential membrane
means “motrice force” of proton which is necessary in ATP synthesis
from Krebs cycle. The concentration of H+ become high in place of
mitocondrial cytosolic and a electric potential is born in this place. This
proton of “ motric force”, of 0.22 mEv, correspond to a level of free
energy de 5.2 Kcal/ proton molecule. The transfer of electron from
NADPH in each every place of conserved energy transmit
conformational exchanges of mitocondrial enzymes.
Scheme 1. Graphic 1
10. • Changes in pH value into fluids of cells can occur because
inversion of electron spin, to hydrogen atoms, with increase of
energy to electrophil oxygen atom from H2O molecules, becoming
trigger for levogir vibrational molecules, as the estimation:
H-O-H>>H-O-H±.
• The energy of parallel spin at electron from fundamental position
(unexciting) will be increased to anti-parallel position spin (exciting)
in value of 0.04*10³ meV. The energy of oscillation for hydrogen
atom is in water is in value of 0.04*10_5 meV and the difference
between exciting state (J=E¹) and ground state (J=Eº) for the
hydrogen atom is in value of 0.059 meV.
• The supply with a potential level of energy (Eº + 0.059 meV) to
electrons of oxygen from water can increase the value of pH. In the
excited state of trans-conformation molecule, it have been showed
that the angle H-H from oxygen atom, becomes more large
108*grades, in comparison with those in ground state which has
105* grades.
•
11. •
• Because of electron redistribution from central Oxygen ion in
water molecule H-O-H, the O½־ ion becomes with two ions of H
more reached in energy and remains in state for more time, as a
biological memory.
• In the normal status, the molecules of water will pulse in liquid like
a hart, with movement in the same plan,( twisting), and in out of
plane ( rocking). The main changes of inter-atomic distance are also
between the atoms of bridge fragment O-H. During of an excitation,
the total length of distance between H and O atom increases with
0.3 A. The van der Waals forces action to distance of 2-3 A and
depends of stearical energy (0.04* 10³ meV).
• I water, designed photo-reactive molecules, which perform
reaction, during energetic excitation is used as a molecule trigger for
followed molecules of water. The network of molecular wires and
molecular dynamic memory can be implemented into molecular
nano-robots, composed from another molecule of different fluids.
•
12. In reaction ADP³ + P2¯ + H2----ATP + H2O, and in reversible sense, terminal
oxygen from ADP has draws the atom P2¯ with formation of intermediate penta-
covalent length and than has place a dissociation of molecular complex in ATP and
H2O. This reaction need of Mg participation and ATP-synthetase, known as comp;ex
H+_ATP-ase or FoF1-ATP-ase, when FO=conductor proton and F1=ATP
synthesized.
In fact, the Mg and Ca participate to activation more than 300-400 enzymes which
transfer group of phosphate in metabolic process and contribute to intermediate
metabolism by degradation of molecular composes with high energy on aerobe way.
The Mg2+ by high electronegativity of its electrons, stabilizes mitocondrial membrane
in opposite with intracellular calcium which products mitochondrial swollen and the its
damage by calcification.
Mg2+ in generally interacts with substrates through inner coordination sphere,
stabilizing anions or reactive intermediates, also including binding to ATP and
activating the molecule through nucleophilic attack of oxygen atom.
In either case, because Mg2+ is only rarely fully dehydrated, as ligand it is more
important rather than the ion itself. The Lewis acidity of Mg2+ (pKa 11.4) is used to
allow both hydrolysis and condensation reactions.
13. The importance of magnesium to proper cellular function can not be
overstated. Deficiency of Mg in nutrients results in disease which affect the
organism. In single-cells organisms such as bacteria and yeast, a low level of
magnesium manifests in greatly reduced growth rates.
Also, Mg has a role in sinthesys of immune-globulins.
A deficiency of Mg can lead to Non-Hodgkin limphomas, Hodgkin Lymphoma
or Lympho-sarcoma.
The Mg2+ ion tends to bind only weakly to proteins (Ka ≤ 105) and this can
be exploited by the cell to switch enzymatic activity on and of by changes in
the local concentration of Mg2+.
Although the concentration of free cytoplasmic Mg2+ is on the order of
1 mmol/L, the total Mg2+ content of animal cells is 30 mmol/L, in plants the
content of leaf endodermal cells has been measured at values as high as
100 mmol/L (Stelzer et al., 1990), and is buffered in storage compartments.
14. The hydration shell of the Mg2+ ion has a very tightly bound inner
shell of six water molecules and a relatively tightly bound second shell
containing 12 – 14 water molecules (Markham et al., 2002). Thus
recognition of the Mg2+ ion probably requires some mechanism to
interact initially with the hydration shell of Mg2+, followed by a direct
recognition/binding of the ion to the protein.
Due to the strength of the inner sphere complexing between Mg2+
and any ligand, multiple simultaneous interactions, with the transport
protein at this level, might significantly retard the ion in the transport
by pore of membrane cells.
Hence, it is possible that much of the hydration water is retained
during transport, allowing action of in electrons carrier of Mg.
15. Was determined and crystal structures of the full-length protozoar
Thermotoga maritima CorA, Mg protein transporter and its cytoplasmic
domain at 3.9 A and 1.85 A resolution, respectively.
The transporter is a funnel-shaped homo-pentamer protein chains with
two trans-membrane helices per monomer.
The cytoplasmic neck of the pore is surrounded, on the outside of the
funnel, by a ring of highly conserved positively charged residues.
Two negatively charged helices in the cytoplasmic domain extend back
towards the membrane on the outside of the funnel and abut the ring of
positive charge. An apparent Mg2+ ion was bound between monomers at a
conserved site in the cytoplasmic domain, suggesting a mechanism to link
gating of the pore, to the intracellular concentration of Mg2+.
Figure 2
16.
17. To date, the ZntA protein of protozoar Paramecium, Mg protein trasporter,
has been shown to be a Mg2+ channel.
The mechanisms of Mg2+ transport by the remaining proteins are
beginning to be uncovered with the first three dimensional structure of a
Mg2+ transport complex.
Magnesium ions (Mg2+) in cellular biology are usually in almost
all senses opposite to Ca2+ ions, because they are bivalent too, but
have greater electronegativity and thus hold on to water molecules
stronger, preventing passage through the channel of membrane.
Thus Mg2+ ions block Ca2+ channels. Magnesium can affect
muscle relaxation through direct action on the cell membrane. Mg++
ions close certain types of calcium channels, which conduct a
positively charged calcium ion into the neuron.
With an excess of magnesium, more channels will be blocked and
the nerve will have less activity.
Scheme 2
18.
19. Traditional medicine along years has confirmed that red, orange and green
vegetables, by reach content of Beta-oydants and Beta-alanina, Fe and Mg,
(Example, Beetroot), have an anti-tumor activity, block development of cancer
cells which have a predominant an-aerob metabolism and activate the system
cyto-chrome oxidase enzyme, on aerobic away, increasing the speed of celullar
breath from mithocondria, in “vivo” and in “vitro’.
Some good sources of magnesium: Green vegetables such as spinach provide
a high cantity of magnesium because of the abundance of chlorophyll molecules
which contain the Mg ion. Nuts (especially almonds) and some whole grains are
also good sources of magnesium.
Figure 3
Too much magnesium may make it difficult for the body to absorb calcium. Not
enough magnesium can lead to hypomagnesemia, manifested by irregular heart
beats, high blood pressure (a sign in humans but not some experimental animals),
insomnia and muscle spasms (fasciculation).
20. Figure 3
Space-filling model of the chlorophyll a molecule, with the Magnesium ion
(bright green) visible at the center of the porphyrin group.
21. ROLE OF Mg to NUCLEIC ACIDS
Nucleic acids have an important range of interactions with Mg2+. The binding
of Mg2+ to DNA and RNA stabilizes its structure; this can be observed in the
increased melting temperature (Tm) of double-stranded DNA in the presence of
Mg2+. Additionally, ribosomes contain large amounts of Mg2+ and the
stabilization by Mg ion is essential to the complex of ribo-proteins.
A large number of enzymes is involved in the biochemistry of nucleic acids
bind Mg2+, using the ion for its both activation and catalysis. Finally, the
autocatalysis of many ribozymes (enzymes containing only RNA) is Mg2+
dependent.
Biological membranes are impermeable to Mg2+ (and some other ions) so
transport proteins must facilitate the flow of Mg2+, both into and out of cells and
intracellular compartments.
22. Indeed, Mg2+-dependent enzymes appear in virtually every metabolic pathway:
specific binding of Mg2+ to biological membranes is frequently observed, Mg2+
being also used as a signal molecule.
In nucleotides, the triple phosphate moiety of the compound is invariably
stabilized by association with Mg2+ in all enzymatic processes.
Normally the body cells communicate by intra-cytoplasmic channel and energetic
potential of membrane cells is 1-2.5 absolute value, as raport:
ATP-ADP/ATP-ADP-IMP.
In conditions of this range has place process of normal division of cells.
If intracellular level of Mg is low, the extra-membrane charges of cells will by not
uniformly distributed and a high positive extra-potential of cell will drive to loss of
contact inhibition of cells, initiating the process of carcinogenesis by effect of
elctromagnetic induction of oscillation, from central malign cells, the molecules
from around malign cells be charged with the same high positive electric potential,
as an energetic tranfer between cells and will be initiated the aberrant processes of
high proteins and enzymes synthesis, characteristically cancer cells.
High level of energy from anaerobic ATP, in 100 time values more than in normal
cells, correspond to a very high membrane potential, carcateriscaly with high rate of
divisions cells
25. CONCLUSIONS:
The mechanisms of Mg2+ transport by the remaining proteins are beginning
to be uncovered with the first three dimensional structure of a Mg2+
transport complex, recent discovered. Figure 4
Natural compounds of Mg can be used in bio-technology to manufacture
of dugs, in conventional classic medicine, in naturist medicine, in
homeopath medicine and in laboratories of molecular biology, in the
experiments for to increase life span of stem cells, cultivated on a specific
biological culture medium