Enzymes and Nucleic Acids: Essential Biomolecules

Posted on Dec 7, 2024 in Biology

Enzymes

Concept: Enzymes are usually proteins that specifically catalyze certain biochemical reactions by binding to the molecule or metabolite that is going to transform, the substrate.

Chemical Nature: Some protein enzymes are not exclusively proteins but are associated with other molecules. The nature of these molecules depends on the enzyme’s activity. These associations are called conjugated enzymes or holoenzymes. Holoenzymes are composed of cofactors and the protein part of the enzyme, the apoenzyme. The cofactors are diverse in nature and may include:

  1. Metal cations such as Zn2+, Ca2+, which bind to the apoenzyme or regulate its activation.
  2. Complex organic molecules: They are called coenzymes when bound weakly to the apoenzyme. When bound tightly to the apoenzyme by covalent bonds, they are known as prosthetic groups. This is the case of heme.

Active Center: One of the most important features of enzyme activity is their specificity in the reaction they catalyze. This property is due to the dimensional conformation of the enzyme’s active site, which is complementary to the substrate molecule that it binds.

Action of Enzymes: The complementarity in the binding of enzyme to substrate has been likened to that between a key and a lock, hence the model is called the lock-and-key model. However, this union cannot be rigid. The binding of the substrate itself induces a conformational change in the enzyme’s active site, which eventually causes the perfect and definitive link between the enzyme and the substrate. This model is called the induced-fit model.

Inhibition: The activity of an enzyme can be modulated through different mechanisms to inhibit or activate it. Enzymatic reactions are regulated by molecules or cellular components that can inhibit them reversibly or irreversibly.

  • Reversible inhibitors: They bind temporarily to the enzyme and are called competitive inhibitors, as they have a similar spatial conformation to the substrate and compete with it by binding to the enzyme’s active center.
  • Irreversible inhibitors or poisons: They bind irreversibly to the enzyme’s active site and completely suppress its activity.

Another form of inhibition is allostery. Various molecules can specifically bind to the enzyme, causing a conformational change in it. This change results in the transformation between the inactive form of the enzyme and the functionally active form, and vice versa. Both conformations of the enzyme are different and stable. These ligands bind to the enzyme in so-called regulatory centers, which are different from the active site.

Nucleic Acids

Nucleosides: Result from the union of a pentose and a nitrogenous base through an N-glycosidic bond between C1′ of the pentose and a nitrogen of the base, with the loss of a water molecule. They are named by adding the suffix -osine to the name of the base if it is a purine base, or the ending -idine if it is a pyrimidine base. If the pentose is deoxyribose, the prefix deoxy- is also added.

Nucleotides: Are the phosphate esters of nucleosides. They are formed by assembling a nucleoside with a phosphoric acid molecule in the form of a phosphate ion, which gives a strongly acidic character to the compound. The ester bond occurs between the hydroxyl group on carbon 5′ of the pentose and phosphoric acid. They are named as the corresponding nucleoside, eliminating the ending and adding the ending 5′-phosphate or monophosphate.

Watson and Crick Model: The spatial structure of DNA was established in 1952 by Watson and Crick. It was already known that DNA was composed of nucleotides of known size and structure, linked by phosphodiester bonds. They took the work of Chargaff, Franklin, and Wilkins on the content of nitrogenous bases and X-ray diffraction as a basis for discovering the structure of DNA:

  1. The DNA molecule is long, stiff, and not folded.
  2. In the molecule, there are repeated structural details.
  3. The base composition varies, but for the same species, the content of purine bases equals that of pyrimidine bases.

Watson and Crick proposed a model that was consistent with the data and allowed understanding the functioning of DNA in the transmission of genetic information:

  1. The DNA double helix is 2 nm in diameter, consisting of two polynucleotide chains wound around an imaginary axis. The nitrogenous bases are located in the interior. The planes of their rings are parallel to each other and perpendicular to the axis of the double helix.
  2. The winding is right-handed (clockwise) and plectonemic, meaning that to separate the two chains, they need to be unrolled.
  3. Each pair of nucleotides is separated by a distance of 0.34 nm, and every turn of the double helix is formed by 10 pairs of nucleotides, resulting in a turn length of 3.40 nm.
  4. The two polynucleotide chains are antiparallel, meaning that the 5′ to 3′ links are oriented in opposite directions and are complementary. In other words, there is a correspondence between the nitrogenous bases.

Biological Importance: DNA is the storehouse of genetic information and the molecule responsible for transmitting to offspring the necessary instructions to build all proteins in a living being. It can make copies of itself through a mechanism called replication, based on the complementarity between the nitrogenous bases of the two strands of DNA. There is some correspondence between the complexity of an organism and the amount of DNA it contains. The more complex an organism, the more different proteins are needed. There is a notable difference in the DNA content of viruses, bacteria, yeast, and multicellular beings. However, within the same group, such as vertebrates, there may be large differences in DNA content, with no significant difference in complexity.

RNA: RNA is formed by the joining of ribonucleotides of adenine, guanine, cytosine, and uracil by phosphodiester bonds in the 5′ to 3′ direction. Besides the four main bases, other derivatives, mostly methylated, can occur. In most organisms, RNA is single-stranded, except for some viruses where it is double-stranded. In some parts of its single-stranded molecule, called hairpins, it may have a double-helix structure as a result of the formation of hydrogen bonds between complementary bases. Areas where there is no complementarity are separated, forming loops. In almost all living organisms, the function of RNA is the same: to direct the synthesis of proteins from the information obtained from DNA.

Messenger RNA (mRNA): It constitutes between 2% and 5% of total RNA. Its function is to copy genetic information from DNA (transcription) and take it to the ribosomes, which are the organelles where protein synthesis takes place. In eukaryotes, mRNA is called monocistronic, while in prokaryotes, each RNA molecule is called polycistronic. mRNA has a short life because it is rapidly destroyed by the action of enzymes called ribonucleases.

Ribosomal RNA (rRNA): It makes up to 80% of total cell RNA. Also called structural RNA, several molecules of this RNA associate with a set of basic proteins to form a ribosome, the organelle where proteins are synthesized.

Transfer RNA (tRNA): Its function is to transport amino acids to the ribosomes, where they unite to form proteins. It consists of a number of nucleotides ranging from 70 to 90. Some areas of the molecule have a double-helix structure, and where there is no base pairing, loops are formed. One feature of tRNA is the presence of nucleotides with nitrogenous bases different from the usual ones. There are 50 different types of tRNA, but all have some common characteristics:

  1. At the 5′ end, there is a triplet of nitrogenous bases with guanine, and there is always free phosphoric acid.
  2. The 3′ end consists of three unpaired nitrogenous bases (CCA), this being the place where tRNA binds to the amino acid to be delivered to the ribosome.
  3. In arm A, there is a triplet of nitrogenous bases called the anticodon, which is different for each tRNA depending on the amino acid it carries. It is complementary to the corresponding codon triplet in the mRNA.

Nucleolar RNA: It is associated with different proteins, forming the nucleolus. It originates in the nucleus from different segments of DNA, known as nucleolar organizers. Once formed, it fragments and gives rise to different types of ribosomal RNA.