Tuesday, February 21, 2017

Oxidative stress - Advantages and disadvantages



Oxidative stress results primarily from an imbalance between molecules potentially dangerous to our cells, the so-called reactive oxygen species, and molecules that protect the oxidative integrity of our cellular structures, as discussed in another post (more information here). When this imbalance favors the former, or disadvantages the latter, we have the condition called oxidative stress.
Oxidative stress is the mainstay of the aging theory, because although we have several antioxidant defenses to protect us, there are always reactive oxygen species that can bypass these defenses, causing little damages that start to accumulate. Furthermore, in the case of smokers, there is permanent oxidative stress, especially at the level of lung cells, since tobacco smoke contains large amounts of reactive oxygen species (and reactive nitrogen species, but I will not talk about them today), which causes the antioxidant defenses in the lungs to be unable to cope completely with the aggressions from tobacco smoke.
But not everything is bad news, because our biochemistry is full of examples where even the most dangerous situations/molecules can be converted into an advantage, at least in some contexts... This is what happens with oxidative stress! Although it is a potentially fatal situation for cells and therefore, most often, is a situation we should avoid, there is a context where oxidative stress is beneficial to our body. I'm talking about the inflammatory response...
In a simple way, when there is an invading microorganism (or other types of stimuli), our organism detects that something is not well, and initiates the inflammatory response. One of the most important cellular components of it is neutrophils, a class of white blood cells. One of the ways neutrophils act, is related to their contact with invading microorganisms. In response to this situation, neutrophils increase their metabolic rate, and the reason is simple: they want to overproduce reactive oxygen species, that means, they want to induce oxidative stress. Of course, this is a controlled process, that is, the stimulation of oxidative stress occurs at a level that can still be effectively eliminated by our antioxidant defenses, but most microorganisms will no longer have this capability. Thus, neutrophils induce oxidative stress, at a level still tolerated by most of our cells, but not tolerated by most microorganisms. In this way, the invasion is controlled and ideally does not cause significant damage to our body.
Therefore, even oxidative stress can be advantageous, as long as properly controlled. It is another notable example of how fascinating is the World of Biochemistry ... ;)

Tuesday, February 14, 2017

Hemoglobin

For higher 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: 
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.

Text written by:
Beatriz Ribeiro
Cláudia Campos
.

Wednesday, February 8, 2017

Oxidative stress - Antioxidants



Recently I have made a 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 an endogenous 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.

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