Amino Acids

• The relative strengths of weak interactions are: covalent bond >350 kJoule/mole, ionic interaction ≈80 kJoule/mole, hydrogen bond ≈20 kJoule/mole, hydrophobic effects ≈10 kJoule/mole, van der Waals forces ≈10 kJoule/mole.
• Amino acids are modified Lehninger Fig 2-7b, with energy state Lower, Lowest, Maximal, Micelle, Therm Stability Greater, Maximal, Lowest.
• Molecules that are ionized, form hydrogen bonds, or share electrons in water are polar by nature and are hydrophilic, reacting with water to dissolve.
• Nonpolar molecules are hydrophobic, do not interact with water, and do not dissolve well in water.
• Charged Hydrophilic (Polar) Amino Acids include Lysine (Lys), Arginine (Arg), Histidine (His), and Aspartate (Asp).
• Acids are any molecules, ions, or functional groups that will donate a hydrogen ion (H+).
• Uncharged Hydrophilic (Polar) Amino Acids include Cysteine (Cys), Serine (Ser), Threonine (Thr), Tyrosine (Tyr), Asparagine (Asn), and Glutamine (Gln).
• Hydrophobic (Nonpolar) Amino Acids include Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Isoleucine (Ile), Methionine (Met), Proline (Pro), Phenylalanine (Phe), and Tryptophan (Trp).
• Must still restrict Phe in diet, and test blood regularly.
• Elevates PAH activity is only effective with PAH activity.
• Bases combine with a H+ ion.
• Many biological molecules possess both acidic and basic groups.
• A zwitterion is a molecule with equal number of positive and negative ions, having no net charge (neutral).
• At a given pH, specific functional groups have a predictable ionization state, based on the pH and pK of the functional group.
• Carbonic Acid / Bicarbonate Anion Buffer System is important in maintaining blood pH.
• H2CO3 ↔ HCO3- + H+ is produced in tissues and combines with H2O (catalyzed by carbonic anhydrase) to form H2CO3, which is rapidly ionized to HCO3- and H+.
• Hemoglobin shifts to T-state (weak binding O2) partly because protonated His bonds more tightly to nearby Asp residue.
• T-state: His-Asp bonded, R-state: His-Asp not bonded.
• T-state: His-Asp, C-term-Lys bonded, R-state: His-Asp, C-term-Lys not bonded.
• Nonpolar aliphatic R groups are hydrophobic and clustered within protein by hydrophobic interactions, providing structure.
• Aromatic R groups, with aromatic ring in side chain, are relatively hydrophobic, with Phe being most nonpolar, Tyr and Trp less so.
• Uncharged polar R groups are soluble in water, more hydrophilic, and form hydrogen bonds.
• Cysteine pairs oxidized to form disulfide bond.
• Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism, caused by defect in phenylalanine hydroxylase (PAH), preventing breakdown of Phe, alternatively caused by tetrahydrobiopterin deficiency, a cofactor needed in PAH reaction.
• Peptide Bond Formation is a process that occurs in a plane, with the directionality of N’ → C’.
• Postranslational Modifications can predict how modification changes properties of the proteins.
• Treatment for PKU is life long diet low in Phe, excluding high protein foods (milk, cheese, eggs, meat, fish), diet drinks and foods with aspartame (contains phenylalanine, Nutrasweet or Equal).
• If pH is < pKa, the protonated form is predicted, while if pH is > pKa, the unprotonated form is predicted.
• PKU is an autosomal recessive disorder (1:25,000) with ethnic predominance in Northern European and Native American ancestry, causing mental retardation and brain damage.
• Positively Charged Polar R Groups are soluble in water and contain + charged amino, guanidino or imidazole groups, respectively, making them strongly hydrophilic.
• In December 2007, Kuvan (tetrahydrobiopterin) was approved for treating PKU.
• Protein phosphorylation is a process that regulates glycogen phosphorylase, which releases glucose-1 phosphate from glycogen.
• Testing for PKU is routine in post-natal screening.
• Cystinuria is an autosomal recessive defect in cystine reabsorption in the kidney and absorption in the small intestines. It has a frequency of < 1/10,000.
• Negatively Charged Polar R Groups are soluble in water and contain a second-charged carboxyl group, making them strongly hydrophilic.
• Protein glycosylation is a process that occurs in Coronavirus Spike, as seen in Nature Structural & Molecular Biology 23, 899–905 (2016).
• Sequence alignment, similarity can be achieved with identical substitutions, similar substitutions, known as "conservative substitutions", and divergent substitutions known as "non-conservative substitutions".
• The amino acid sequence determines protein structure and function.
• Urolithiasis: Crystals or stones inurine, kidneys and bladder
• Cystinuria/urolithiasis treatments: Lower Cysteine and Methionine in diet, increase fluid intake to help flush crystals. Drugs to alkalize urine, increase solubility and reduce crystallization. Surgical removal of stones.