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LECTURE of the AGEING reasons (1/2)

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(1 / 2) of the reasons LECTURE AGEING


Nonenzymatic glycosylation of proteins and aging

Centenarians

When studied those whose age exceeded 100 years,
were in this group of drinkers and drinkers, smokers and nonsmokers, with
high and low cholesterol, calm and explosion, and practitioner
nieruchawi. Among these factors are not found significant differences in
the rest of society. However, they all had certain characteristics
joint strongly differentiates them from others. These were: an exceptionally
low blood sugar, triglycerides and very low relatively low levels of
insulin.


Can you relate to the coexistence of longevity and performance
biochemical direct cause-effect relationship? Research
recent years, at least partially give a positive answer to this
question. Seems to be indisputable role of sugar and insulin in the
process. Triglycerides appear to be the only effect
increase in sugar and insulin in the blood and in themselves do not accelerate the
significant aging.

In the current article will try to bring a bit mechanisms
the impact of high levels of sugar in the pace of the aging process.



Nonenzymatic glycosylation

The basic mechanism of the negative effects of circulating
Blood sugar is a non-enzymatic binding to different molecules
protein and change its properties. This process is called
nonenzymatic glycosylation. The term "non-enzymatic means that
this process occurs spontaneously, without any special reaction accelerators
chemical, such as enzymes. It means so that the basic parameter
designating the overlap of the reaction rate at a given moment is
actual concentration of glucose (fructose, galactose) in the blood. The higher
is the concentration, the faster the reaction. Another parameter,
which could affect the reaction rate is temperature. Higher
temperature facilitates the chemical reaction of each incident, since the molecule
You will then have more energy to overcome the energy barrier defending
before the occurrence of the reaction.

From the outset I wish to emphasize that the process of glycosylation
occurs in our body very slowly, and the special mechanisms
Defensive non-stop "clean up" glycosylated proteins and build their new
place. An example of the process used today in the glycosylation
medicine is the determination of glycosylated hemoglobin in
monitoring of diabetes, which reflects average blood sugar
blood in the last 6-8 weeks. During the life blood for up to
120 days on average glycosylation is normally around 10%
hemoglobin molecules. As in the blood cells at any given time about
different ages, the average glycosylated hemoglobin of approximately
5%.

In diabetes, the average concentration of sugar increases such as 2-fold (from
approximately 100 mg% to about 200 mg%), plugging of hemoglobin increases
also approximately doubled. However, because cells
glycosylated live shorter, the average glycosylated hemoglobin
increases slightly less than 2x.



Stages of glycosylation

Interaction with sugar molecules to proteins is
two stages. The first step is reversible, meaning that after reaching
equilibrium reaction occurs at the same speed in both directions.
State of equilibrium is reached after approximately 1 month, which in practice means
that for proteins with rapid turnover in the body, it is not achieved
never. Proteins miss uglikozylowane be spread, and in their place
creates nieuglikozylowane. The second stage is irreversible.
Liable to the protein remaining long in the body, such as collagen
(White skin, tendons, cartilage, bone). The result of this step is
they are so called. advanced glycation end products - (Advanced
Endproducts glycation, AGE). Abbreviation used in the literature is here for AGE
so interesting that the word "age means in English is getting old
up. AGE so we understand certain chemicals, which
complicated names will not be quoted, which can be determined
examined tissues and fluids, and the number of which indicates
progress of an irreversible process of glycosylation.



Examples of glycosylation

Biological effects of these processes are multiple and
perhaps not all are yet unknown. What is known today?

Albumin - glycosylation impairs its transport functions.
Decreases its ability to transport bilirubin and long chain
fatty acids.

Erythrocyte membrane proteins - their glycosylation reduces its
elastic properties, thus decreasing the ability of erythrocytes to
deformation in the capillaries.

Cathepsin B - The enzyme involved in the conversion of proinsulin
insulin. Under the influence of glycosylation inhibited.

Antithrombin III - its glycosylation processes leads to the advantage
solidification process of removing blood clots.

Superoxide dismutase - an enzyme that is part of the system
antioxidants. Its inhibition under the influence of glycosylation leads
the development of so-called. oxidative stress in the cell. Put simply: free
radicals are removed more slowly, thus increasing their harmful effects.

Apolipoprotein B - main protein of LDL. Glycosylation in
binding site to the receptor causes that this fraction is slower
removed from the blood. In total, nothing bad happens, so that increases
bit LDL in plasma, which is often seasoned investigator to be needlessly
of stress. Knowing we generally prevailing social phobia
high LDL, once at this point I will add that the question of the level of LDL in
blood also depends on many other factors. As the level of
blood component is actually a wide range of irrelevant
evolutionarily not evolved mechanisms to regulate its
levels within narrow limits. There is therefore a large variation
Individual levels of plasma LDL. In the course of evolution, individuals with high or
low levels of LDL were not simply eliminated from the population.

Collagen - under the influence of glycosylation, the number of bonds
cross between molecules of collagen, which makes the increase
stiffness of collagen fibers is also reduced their
solubility and susceptibility to enzymatic digestion, which makes it difficult
regeneration.

Nucleic acids (DNA) - are very long molecules of living,
can thus be significantly modified under the influence of sugar. This may
lead to changes in the genetic material. Glycosylation of DNA can be
explanation of why the famous cloned sheep Dolly so quickly
grown old. The reason could be higher than normal
Glycosylation of genetic material.




tbc ...

MD Piotr Krzysztof Michalak
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LECTURE of the AGEING reasons (1/2)
 

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