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Video about ethanol metabolism

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Cartoon - electrons

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Metabolic map - Apoptosis

Video about DNA repair

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Amino acids with aromatic side chains

By definition, a molecule is considered aromatic when in its constitution there is at least one derivative of benzene, ie, a cyclic structure with 6 vertices (all carbon atoms!), and 3 double bonds (in fact, as I said in other posts, they are not 3 double bonds, but 6 partially double bonds, with bond order of 1.5). Therefore, when, in a molecule, there is at least one such structure, the molecule is considered aromatic.

Probably some of you may be questioning yourself why to use the concept of "aromatic". In fact, most of the substances we know that have flavour (e.g., cinnamon or clove), have their aroma exactly due to the presence of molecules containing aromatic rings, in this particular case, cinnamaldehyde and eugenol, respectively. It is the delocalized electron cloud of the derivatives of benzene rings that give the fragrance to these (and many other!) molecules, and hence the chemical definition of aromatic is clearly related to the "physiological" setting of aromatic.

Let us return to amino... there are 3 that contain a derivative of the benzene ring on its side chain and are, therefore, referred to as aromatic amino acids:

Phenylalanine - the name itself explains the composition of this amino acid. In a previous post I talked about the nonpolar amino acids with aliphatic side chains, among whom was alanine (this post). Phenylalanine is no more than an alanine with a phenyl group, ie with a benzene ring. Since it only has carbon and hydrogen in its side chain, it is a nonpolar chain.

Tyrosine - this aminoacid is a hydroxylated phenylalanine. In fact, it only differs from phenylalanine because it presents a hydroxyl group on the aromatic ring, more precisely on a diametrically opposed carbon to the alpha carbon position. This hydroxyl group gives it some polarity, with the resulting side chain being therefore amphipathic.

Tryptophan – it is the amino acid with the more complex side chain comprising two cyclic structures: one is a benzene derivative, another is a heterocycle (ring composed of 2 different atoms, carbon and nitrogen in this case). These two fused rings form a functional group called indol group, which is amphipathic, since the nitrogen confers some polarity. Tryptophan is very important from a biological standpoint, because in addition to being used in the production of proteins, it is also the precursor of many important molecules, such as, for example, serotonin.

The tyrosine and tryptophan have an important characteristic, which is that of absorbing ultraviolet radiation. Due to this, the proteins having these amino acids (almost all!) present the ability to absorb UV light. In fact, phenylalanine also absorbs UV radiation, but in much smaller amount than the other aromatic amino acids, because the chemical modifications of the benzene ring (hydroxyl group in the case of tyrosine, and embedding the indole group in the case of tryptophan) significantly increase the UV absorptive capacity of aromatic rings.

Cartoon - Krebs cycle

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Cartoon - Aminoacids

Amino acids with nonpolar aliphatic side chains

As I mentioned here on the blog, in an earlier post (this post), the standard amino acids differ in the chemical composition of their side chains. The 20 standard amino acids can be divided in 5 groups, according to the physico-chemical properties of the side chain, in particular, according to their polarity. Before starting to talk about this division, I want to mention that it is a division that involves some ambiguities, which I will highlight as they appear in the posts that I will devote to this matter.
I'll start by talking about the amino acids with nonpolar aliphatic side chain. First of all, it should be explained what does it means nonpolar and aliphatic. Nonpolar means that there are no significant asymmetries in the distribution of electrons on atoms. Stated more simply, if a molecule (or a side chain) it is non-polar, it contains atoms with similar electronegativities. As mentioned in a previous post (this post), if a molecule is composed only of carbon and hydrogen, it is considered non-polar. Similarly, if a side chain of an amino acid is composed only of carbon and hydrogen atoms, it is considered to be nonpolar. Regarding the term "aliphatic", this relates to the absence of aromatic rings, which are benzene ring derivatives; therefore they are cyclic structures with six vertices, all of them corresponding to carbon atoms and 3 double bonds therein (in fact they are not three double bonds, instead they are six bonds with the connection order of 1.5, but this would complicate things and may be considered three double bonds). Therefore, all amino acids having in its side chain only carbon and hydrogen atoms and that show no aromatic rings, belong to the class of amino acids with nonpolar aliphatic side chains.

They are:

Glycine – it is the simplest amino acid with a side chain consisting only of hydrogen. As the hydrogen is too small to have a major role in the interaction with other amino acid side chains, and do not have by itself a polar (or nonpolar) significant behavior, this amino acid appears in this category by deleting parts, namely because in the other categories did not make sense to include it. Glycine has the distinction of being the only standard amino acid that does not have stereoisomers because its a carbon is not chiral because it is not connected to four different substituents.
 

Alanine – its side chain is a methyl group (-CH3), which fits perfectly in the definition of nonpolar aliphatic side chain.

 Valine, leucine and isoleucine - their side chains are more complex than that of alanine, but they are composed exclusively of carbon and hydrogen atoms.

 

Methionine – another amino acid that appears in this group somewhat by a process of elimination. The sulfur atom is an inner position of the chain (is a thioether group), and does not significantly affect the polarity thereof.
 

All amino acids in this group will tend to establish London dispersion forces (so-called "hydrophobic interactions") with neighboring amino acids and, therefore, in a 3D structure of a protein, they tend to appear in proximity to each other.

I just wanted to finish with an idea that is often said in the wrong way. The amino acids shown in this post are not nonpolar amino acids, they are amino acids with nonpolar side chains. No amino acid is nonpolar because they have two very polar groups (amino and carboxylic) connected to a carbon.

Video about aminoacid structure

Metabolic map about aminoacid catabolism and urea cycle

Cartoon - Last Words

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Cytochrome c and apoptosis

As mentioned in one of my last posts, cytochrome c is a small protein, essential for mitochondrial respiratory chain, where it acts as an electron carrier between the complex III and complex IV. Besides this very important function, cytochrome c is also an important activator of programmed cell death, or apoptosis; more specifically, it is an activator of the intrinsic pathway of apoptosis. Because of this dual role, cytochrome c is often classified as "a central molecule for life in our oxygen world, and simultaneously a key that opens the door to death."

While apoptosis is a form of cell death, it is a fundamental mechanism for keeping the homeostasis of our body. In fact, when a cell accumulates irreparable damage (in DNA or in another biomolecule), when placed in an environment where it may be potentially dangerous to the remaining cells (shortage of nutrients, detachment from the surrounding cells, deprivation of growth factors, infection, autoreactive leukocytes, etc.), or when it is not important in the body (natural selection of neurons, for example) tends to commit suicide - apoptosis. This obvious idea, but at the same time strange, suggests something that I often refer in my classes, that is the fact that multicellular organisms must be regarded not as a living being composed of many cells, but as a living community, where each cell has its role, and lives in community with the others.

Apoptosis is a complex process that involves many mediators and that ultimately leads to the activation of enzymes that promote cell self-digestion. Caspases are a class of proteases that plays a key role in the apoptotic response. Overall, there are defined two apoptosis activation mechanisms: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is also sometimes referred to as pathway initiated by the cytochrome c, since this protein is the main actor in early apoptotic response. Several stimuli can lead to the release of cytochrome c from the intermembrane space into the cytosol. When this happens, it starts the activation of caspases. Under normal conditions cytochrome c does not abandon the intermembrane space, since it interacts with an existing glycerophospholipid in the inner mitochondrial membrane, cardiolipin. The high density of negative charges of the phospholipid electrostatically attracts the positively charged cytochrome c. In addition, a hydrophobic tail of the lipid is inserted in a hydrophobic cavity of the protein, enhancing the interaction between both molecules. It is the damage caused on cardiolipin which can make these interactions to be destroyed and the cytochrome c released.

Once in the cytosol, cytochrome c promotes the release of calcium stored in the endoplasmic reticulum, increasing the ion concentration in the cytosol. One of the functions of calcium is the stimulation of the release of more cytochrome c into the cytosol, thus causing a positive feedback loop. A further consequence of the presence of cytochrome c in the cytosol is the activation of caspase 9, which in turn activates caspases 3 and 7, and the fate of the cell is irreversible - death by apoptosis!

T-shirt - Biochemistry (4)

Rap music about Biochemistry

Cartoon about (inexact) science

Metabolic map about cholesterol metabolism regulation

Cellular respiration - Cytochrome c

The cytochrome c is a small protein with 104 amino acids and a mass of about 12 kDa (12.233 kDa in humans). As a consequence of its small size, it is highly conserved among different mammalian species; for example, the human cytochrome c is identical to the chimpanzee! It is a heteroprotein because beyond its amino acid, it contains also an heme group as a cofactor, which is bound to cysteines 14 and 17. It is a hydrophilic protein, highly soluble (solubility ~100 g/L), which is located in the mitochondrial intermembrane space, where it plays a key role in the mitochondrial respiratory chain, though it does not belong to any of the four complexes.
The function of the cytochrome c is to receive electrons from the complex III, and deliver them to the complex IV.  

To acomplish this function, its heme group, as any heme group, has an iron ion that can oscillate between two different oxidation states (Fe²⁺ and Fe³⁺). Since it has only 1 heme group, it can carry only one electron at a time. This feature has two very important consequences:

1. To deliver the 2 electrons from NADH or FADH₂ to O₂ in cellular respiration, it is required 2 molecules of cytochrome c.
2. O2, which is the final electron acceptor of the complex IV, receives one electron at a time, which means that it converted to, even temporarily (in most situations!), a free radical, which potentiates the oxidative stress.
Other functions less characterized of citocromoc are its involvement in catalytic hydroxylation reactions, aromatic oxidation and peroxidation. Also, it appears to be important to the catalytic activity of the nitrite reductase enzyme.

Finally, a very important characteristic of cytochrome c is that it can function as an activator of the intrinsic pathway of programmed cell death, a process referred to as apotose. Soon I will post more information on this subject...