Friday, February 17, 2017
Tuesday, February 14, 2017
Hemoglobin
Forhigher animals, simple diffusion mechanisms in body fluids are not an
efficient way to meet the oxygenation needs of their tissues and
cellular material. To the low area/volume ratio of these living beings,
it is added the fact that O2 is a molecule that is essentially
insoluble, which makes its transport even more difficult. The solution
then passes through carrier proteins, associated with erythrocytes -
hemoglobin, to which the following lines refer.Hemoglobin is an
oligomeric protein and is generally a metalloprotein consisting of about
600 amino acids, arranged in 2 alpha chains and 2 paired beta chains in
a quaternary globular structure. The four chains constitute the organic
part of the molecule, and are attached to heme prosthetic groups
(consisting of a porphyrin ring and a transition metal: Fe2+) which have
affinity for the O2 molecules because of the electron configuration. It
is the Fe2+ that assumes this function, always in its ferrous form, and
the ferric form - Fe3+ - is not able to bind O2, being at the same time
more unstable and prone to the formation of reactive species. Fe2+ has
one O2 binding site and this bond as expected would be reversible to
allow oxygen to be transported to where it is needed. Due to this
binding, there is a change of color in human blood, from bright red when
it is in its oxygenated form, to a more purplish tone in its venous
phase. Some molecules such as CO2 and NO have a higher affinity for the
heme group, "expelling" O2 molecules from erythrocytes, which explains
their toxicity to the organism.
Porphyrias are genetic diseases related to porphyrin of the heme group.
Examples are acute intermittent porphyria and accumulation of
uroporphyrogen I each with specific symptoms.
Concerning the coordinated transport of O2, CO2 and H+, the mechanism is as follows:
Examples are acute intermittent porphyria and accumulation of
uroporphyrogen I each with specific symptoms.
Concerning the coordinated transport of O2, CO2 and H+, the mechanism is as follows:
O2 binds cooperatively to hemoglobin (this means that the bonds promote
more bonds) and then the affinity of hemoglobin varies with pH. In an
acidic environment, H+ and CO2 cause the release of O2 whereas in a
basic medium, O2 causes the release of H+ and CO2. This is the so-called
Bohr effect(reciprocal effect): CO2 + H2O <-> HCO3- + H+
The dead erythrocytes release the heme group generating: Fe3+ (which is
recycled) and bilirubin (which is excreted in the liver). The latter may
have a negative effect if released into the blood because it causes
jaundice, or a positive antioxidant effect especially as an antioxidant
of the membrane, because it collects two hydroperoxide radicals, having
about 1/10 the efficiency of vitamin C.
more bonds) and then the affinity of hemoglobin varies with pH. In an
acidic environment, H+ and CO2 cause the release of O2 whereas in a
basic medium, O2 causes the release of H+ and CO2. This is the so-called
Bohr effect(reciprocal effect): CO2 + H2O <-> HCO3- + H+
The dead erythrocytes release the heme group generating: Fe3+ (which is
recycled) and bilirubin (which is excreted in the liver). The latter may
have a negative effect if released into the blood because it causes
jaundice, or a positive antioxidant effect especially as an antioxidant
of the membrane, because it collects two hydroperoxide radicals, having
about 1/10 the efficiency of vitamin C.
Text written by:
Beatriz Ribeiro
Cláudia Campos
.
Wednesday, February 8, 2017
Oxidative stress - Antioxidants
Recently I have madea post about oxidative stress (you can read it here), in which,
of course, I gave some prominence to the reactive oxygen species. Well, today
I'm going to talk about the "good ones", that is, the antioxidants...
The word "antioxidant" is probably the word most often heard in
social media ads, whether in the context of food, cosmetics, etc. And, in fact,
we can (and should!) ensure a high exogenous supply of antioxidants, being this
an important issue in different contexts. What possibly fewer people know is
that we already have several internal antioxidants. Therefore, we can already
divide the antioxidants into 2 categories:
- Exogenous antioxidants, which are
those that we obtain mainly from the diet;
- Endogenous antioxidants, which are
those that we produce in our cells and that, under normal conditions, are
always present in them.
Another possible classification is as follows:
- Enzymatic antioxidants, which are
enzymes that we produce and whose function is to eliminate reactive oxygen
species. For example, there is an enzyme, called superoxide dismutase that
catalyzes the conversion of 2 superoxide anions (that are free radicals), to a
hydrogen peroxide molecule (which, although being a reactive oxygen species, is
not a free radical). Another example is catalase (you can read more about thisenzyme here), which converts hydrogen peroxide into two products
potentially harmless to our biomolecules, water and oxygen.
- Non-enzymatic antioxidants, which
are molecules that function as antioxidants because they react with reactive
oxygen species, promoting their inactivation. In the background, they are
molecules that "generously" put themselves at the forefront of the
battle against the pro-oxidants. Therefore, these pro-oxidants will react with
them, promoting their oxidation. This situation is beneficial, because it is
the antioxidants that end up getting oxidized, sparing our biomolecules from
oxidative damage. These non-enzymatic antioxidants often have in their
composition benzene rings which stabilize the presence of a possible unpaired
electron, and may also react with one another so that their unpaired electrons become
paired.
Within this class we have glutathione, for example, which is anendogenous antioxidant very important for red blood cells (and for other cell
types...) and that reacts with peroxides undergoing oxidation. When it
undergoes oxidation, it dimerizes with another oxidized glutathione. We also
have some molecules that are exogenous antioxidants, namely vitamin C and
vitamin E, which are very important antioxidants for our plasma and for our
membranes, respectively. Note that there are many vitamins that do not have
antioxidant function, that is, this characteristic can not be generalized to
all other vitamins. There are also several antioxidants that are not
indispensable to our metabolism, but they contribute to its good functioning,
belonging to the class of bioactive compounds of the diet. Flavonoids or
lycopene from tomatoes are good examples of this.
Therefore, if we look at the two classifications, it is easy to see that the
exogenous antioxidants are always non-enzymatic, and that the endogenous
antioxidants can be enzymatic or non-enzymatic. Regardless of the class where
they are inserted, they are extremely important molecules and if we can
guarantee an adequate contribution of them, surely we will be better prepared
to deal with oxidative stress.
Monday, February 6, 2017
Thursday, February 2, 2017
Glucagon
Glucagon is derived from the Greek words gluco (glucose) and agon(agonist). It is a single-chain polypeptide with 29 amino acids,
produced in the α-cells of the islets of Langerhans, located in the
endocrine portion of the pancreas. This protein is important in the
metabolism of carbohydrates. Its function is to increase glycemia by
acting as an insulin antagonist. In a hypoglycaemia, glucagon is
released into the bloodstream and acts mainly in the liver, where it
binds to specific receptors on hepatocytes (which store glycogen),
stimulating them to produce and then release glucose. This mechanism is
called glycogenolysis. After glycogen stores cease, the liver
synthesizes glucose through gluconeogenesis.Thus, under normal
conditions, glucose ingestion inhibits glucagon secretion. During
fasting, there is a decrease in hepatic glycogen, a decrease in
glycolysis in the liver, a stimulation of gluconeogenesis, a stimulation
of fatty acid oxidation in adipocytes and increase of serum levels of
this protein. An important function of glucagon is to maintain the
concentration of glucose high enough for the normal functioning of
neurons, preventing seizures or hyporglycemic coma in normal fasting
situations, such as in nighttime sleep.
Glucagon secretion is
controlled physiologically not only by the hypoglycemia, but also by low
levels of fatty acids, hyperaminoacidemia, vagal stimulation and
adrenal system stimuli, such as stress or physical exercise. Increased
glucagon in the blood will activate lipase from fat cells, inhibit the
storage of triglycerides in the liver, inhibit the reabsorption of
sodium by the kidneys, increase cardiac output, increase the secretion
of bile and inhibit the secretion of gastric acid.
In the cases of
pathology, high levels of glucagon in the blood may be present related
to glucagonoma, a rare neoplasm of the α-cells of the pancreas, causing
increased glucose and lipid levels, decreased levels of amino acids,
anemia, diarrhea and weight loss. It is also observed the appearance of
migratory erythema, characterized by the presence of erythematous
blisters in the lower abdomen, buttocks, perineum and groin. Diabetes
mellitus often results from the imbalance between the hormones insulin
and glucagon present in this neoplasm.
Glucagon can be used in dental
emergencies as in severe hypoglycemia, common in an uncontrolled
diabetic. It can be administered intramuscularly, causing the rapid
increase of glucose levels in the
blood.
Text written by:
- Catarina Capelo
- Dina Nair
- Marta Santos
- Samyra Matni
Wednesday, February 1, 2017
Monday, January 30, 2017
Oxidative stress (general considerations)
Today
I decided to make a post on a very important topic, oxidative stress. This
subject is often referred to in biochemistry classes (and not only!), but it is
not always clear to the speaker or to the audience, what it actually
represents.
Nevertheless,
the idea is simple to understand ... As I say many times in my classes, we have
a bad habit, which kills us slowly, without exception: we spend our lives breathing
oxygen! And
this molecule, so important for our biochemistry, in particular for aerobic
metabolism, is what kills us slowly, and makes us grow old. And
do not hesitate, if we do not die of an accident, or of some illness, we will
die because we have been breathing O2 during our life! :)
So,
what does oxygen contain that makes it so dangerous? Basically
nothing, that is, the molecule itself is harmless to our molecules/cells. The
problem is in its susceptibility to suffer partial reductions, that is, to
capture electrons. In
fact, we are continually forming the so-called reactive oxygen species, which
are essentially 3: the hydroxyl radical (free radical), the superoxide anion
(free radical) and hydrogen peroxide. Of
these 3, the first two are more aggressive because they are free radicals. Free
radicals are molecules that have an unpaired electron (which is why they are
represented with a black speckle, which is that unpaired electron).
The
electrons have a serious problem, they do not like to walk alone, so they will
look for "companionship" in the first molecule that appears ahead, be
it a lipid, a protein or a nucleic acid. That
is, reactive oxygen species are highly reactive molecules, they are powerful
oxidizing agents, which will react with our biomolecules, removing an electron
and altering/destroying them. And
the problem is that although the free radical ceases to be when it picks up an
electron, the molecule with which it reacts becomes a free radical, giving rise
to a destructive chain process.
To
counteract this, our cells have several defenses, called antioxidants. Therefore,
oxidative stress arises when we have an imbalance between the pro-oxidants
(reactive oxygen species and reactions that produce them) and the antioxidants
(processes that prevent the formation and/or action of the pro-oxidants),
favoring the
first, or disfavoring the seconds.
electrons have a serious problem, they do not like to walk alone, so they will
look for "companionship" in the first molecule that appears ahead, be
it a lipid, a protein or a nucleic acid. That
is, reactive oxygen species are highly reactive molecules, they are powerful
oxidizing agents, which will react with our biomolecules, removing an electron
and altering/destroying them. And
the problem is that although the free radical ceases to be when it picks up an
electron, the molecule with which it reacts becomes a free radical, giving rise
to a destructive chain process.
To
counteract this, our cells have several defenses, called antioxidants. Therefore,
oxidative stress arises when we have an imbalance between the pro-oxidants
(reactive oxygen species and reactions that produce them) and the antioxidants
(processes that prevent the formation and/or action of the pro-oxidants),
favoring the
first, or disfavoring the seconds.
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