Connective Tissues
Collagen
Elastin
Tropocollagen
Superhelix Fibers
Triple-Helix Structure
Hierarchical
Lattice Network
Three Protein Chains
Covalent Carbon Bonds
Polypeptide Chains
Alpha Chains
Glycine-X-Y
Proline
Hydroxyproline
Lysine
Hydroxylysine
Hyaluronic Acid
Negatively Charged
Polysaccharide
Organic Acids
Tricarboxylic

Examples of Triple Helices:

Triplex DNA
Triplex RNA
Collagen Helix
Collagen-like Proteins

Post-Translational Hydroxy Modification

Post-translationally modified hydroxyproline can enter into favorable interactions with water, which stabilizes the triple helix. Proline hydroxylation requires ascorbic acid (vitamin C).

The individual helices are also held together by an extensive network of amide-amide hydrogen bonds formed between the strands.

Superhelix Electrostatic Interactions

Charged ends: Short N-terminal and C-terminal "triblock" peptides with oppositely charged amino acids.

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Glycine buffers hydrochloric acid (HCl) by reacting with it to form glycine hydrochloride and by having its own buffering groups resist changes in pH.

Formation of glycine hydrochloride: Glycine and HCl react to form glycine hydrochloride, which is the salt where the glycine molecule is protonated and forms an ionic bond with the chloride ion.

Glycine buffers HCl by using its amino and carboxyl groups to react with and neutralize the strong acid. When HCl is added to a glycine solution, it protonates the negatively charged carboxylate group on the zwitterionic form of glycine, forming the neutral glycine form and the glycine hydrochloride salt. This process resists a large drop in pH because the added 𝐻+ ions from the HCl are consumed by the glycine, which has a pKa value of approximately 2.35 for the carboxyl group.

Glycine's zwitterionic form: In aqueous solution, glycine exists primarily as a zwitterion with a net neutral charge, featuring a positive charge on the amino group (−NH+3) and a negative charge on the carboxylate group (−COO−).

Protonation by HCl: When you add a strong acid like HCl, the 𝐻+ ions from the acid will react with the most basic site on the glycine molecule, which is the carboxylate group (−COO−).

Buffering effect: This reaction consumes the added 𝐻+ ions, preventing a drastic decrease in pH. The buffer capacity is maintained as long as there is a significant concentration of both the carboxylate (−COO−) and the protonated carboxyl (−COOH) forms of glycine present.

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Amino acids like histidine, arginine, and lysine can help buffer (stabilize) the pH of hydrochloric acid solutions because of their basic side chains that can accept protons. Sugars like glucose, galactose, sucrose, and trehalose can also help stabilize proteins in acidic conditions, but their primary function is not buffering, unlike amino acids.

Sugars can increase the stability of proteins in acidic solutions. However, their stabilizing effect is generally considered a form of preferential exclusion, where the sugar molecules preferentially stay in the bulk solvent, forcing the protein to adopt a more stable conformation that minimizes its surface area exposed to the solvent, rather than acting as a buffer.

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Explanation of Preferential Exclusion

Mechanism: When certain solutes (like sugars or polyols, known as osmolytes) are added to a protein solution, they are thermodynamically unfavorable in the protein's microenvironment. The system minimizes free energy by "excluding" these solutes from the protein surface, effectively creating a shell around the protein that is richer in water than the bulk solution.Steric and Charge Effects: This exclusion is primarily due to steric hindrance (the size of the solute molecule) and repulsion from charged groups on the protein surface, especially at specific pH values that affect protein charge.Biological Relevance: This process is crucial in biological systems for stabilizing protein structures. The excluded solutes (osmolytes) help prevent protein denaturation by making the unfolded state (which would require a larger exclusion volume) even more thermodynamically unfavorable than the native, folded state.

While solution pH can modulate the charge of a protein and thus affect the magnitude of preferential exclusion, preferential exclusion is a separate thermodynamic concept related to the interaction of macromolecules with cosolvents and water, not a mechanism of pH regulation itself.

Protein Compaction: To minimize this unfavorable interaction, the protein equilibrium shifts towards more compact, ordered native states with the smallest possible surface area exposed to the solution.

Stabilization: This compaction stabilizes the protein against unfolding or aggregation, which typically involves intermediate, expanded states.

HCl acts as a catalyst in the hydrolysis of sucrose into glucose and fructose, a separate chemical reaction that occurs in an acidic environment.

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HCl is a strong, inorganic mineral acid because it does not contain carbon.

Betaine HCl:
Betaine Trimethylglycine
Glycine Anino Acid (Nitrogen)
Hydrochloride (Hydrogen)

Salammoniac (ammonium chloride) and vitriol (hydrated sulfates of various metals), which he distilled together, thus producing the gas hydrogen chloride. In doing so, al-Razi may have stumbled upon a primitive method for producing hydrochloric acid, dissolving it in water, hydrochloric acid may be produced.

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Organic acids Oleic acid (OA) and Madecassic acid (MA), have been found to act as potent telomerase activators in research settings, suggesting a direct potential for organic acids to influence telomere biology.

Hyaluronic Acid (HA)
Chemistry: HA is a naturally occurring sugar molecule (glycosaminoglycan or polysaccharide) found in the human body, particularly in the skin, joints, and eyes.
Function: Its primary role is to attract and retain water, providing lubrication and hydration.

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Tricarboxylic acid (TCA) related post-translational modifications stabilize the collagen triple helix by engaging in hydrogen bonding and coordinating with ions, which effectively increases the structural integrity and thermal stability of the protein.

How Tricarboxylic Acid Modifications Affect Collagen Direct Modification via Intermediates: While not a canonical enzymatic modification within the cell, intermediates from the TCA cycle can interact with collagen. Succinate (succinic acid), a TCA cycle intermediate, has been shown to bind to collagen via hydrogen bonding, encouraging and accelerating the mineralization process in tissues like bone and dentin.

Hydrogen Bonding Enhancement: The carboxylic groups (which can lose H+) ions) in these molecules, such as succinic acid, can form direct or water-mediated hydrogen bonds within the collagen matrix. The increased number and strength of these bonds help "stitch" the individual collagen strands together, significantly raising the thermal stability and overall mechanical strength of the triple helix structure.

Ion Coordination (H+) Ions and Calcium): The presence of multiple negatively charged carboxylate groups (formed by the loss of H+) ions at physiological pH) allows these molecules to coordinate with positive ions, particularly calcium ions. This coordination is a critical factor in regulating the formation and organization of the apatite crystals during bone mineralization, further stabilizing the collagen matrix and the tissue architecture.

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Mycotoxins
Aflatoxins
Ochratoxin A (OTA)

hydroxylation, oxidation, and sulfation are key biotransformation reactions that living organisms use to detoxify or "neutralize" mycotoxins. The term "electrolyte" is not a specific biotransformation mechanism itself but refers to ions essential for biological processes, which are involved in the overall metabolic environment where these reactions occur.

Biotransformation typically involves two phases to convert fat-soluble mycotoxins into more water-soluble compounds that can be easily eliminated from the body. The goal is often to produce less toxic or non-toxic metabolites.

Phase I reactions introduce or expose polar functional groups (like hydroxyl groups) to increase water solubility.

Hydroxylation: This process adds a hydroxyl (-OH) group to the mycotoxin molecule, often catalyzed by cytochrome P450 (CYP) enzymes. This increases the mycotoxin's polarity and generally reduces its toxicity.

Oxidation: Various oxidoreductase enzymes, such as laccases, oxidases, and peroxidases, catalyze oxidation reactions that modify the mycotoxin's structure, breaking down toxic components.

Other Phase I reactions: The body also employs other reactions like reduction, de-epoxidation, and hydrolysis during this phase.

Phase II reactions involve conjugating the mycotoxin (or its Phase I metabolite) with a large, hydrophilic endogenous molecule, making it highly water-soluble for excretion.

Sulfation: This is a major conjugation pathway where a sulfate group is added to the mycotoxin structure by sulfotransferase (SULT) enzymes. This modification significantly increases water solubility and typically leads to rapid elimination of the much less toxic or non-toxic product.

Glucuronidation: Similar to sulfation, this involves the addition of a glucuronic acid moiety, catalyzed by UDP-glucuronosyltransferases (UGTs), which is another primary route for detoxification and elimination.