The amino acids buffer system

Amino acids contain in their molecule both an acidic (− COOH) and a basic (− NH₂) group. They can be visualized as existing in the form of a neutral zwitterion in which a hydrogen atom can pass between the carboxyl and amino groups. 

By the addition or subtraction of a hydrogen ion to or from the zwitterion, either the cation or anion form will be produced 

Thus, when OH⁻ ions are added to the solution of amino acid, they take up H⁺ from it to form water, and the anion is produced. If H⁺ ions are added, they are taken up by the zwitterion to produce the cation form. In practice, if NaOH is added, the salt H₂N - CH₂ - COONa would be formed. and the addition of HCl would result in the formation of amino acid hydrochloride.

Acids and bases can be classified as proton donors and proton acceptors, respectively. This means that the conjugate base of a given acid will carry a net charge that is more negative than the corresponding acid. In biologically relavent compounds various weak acids and bases are encountered, e.g. the acidic and basic amino acids, nucleotides, phospholipids etc.

Weak acids and bases in solution do not fully dissociate and, therefore, there is an equilibrium between the acid and its conjugate base. This equilibrium can be calculated and is termed the equilibrium constant = K_a. This is also  referred to as the dissociation constant as it pertains to the dissociation of protons from acids and bases.

In the reaction of a weak acid:

HA <-----> A^- + H⁺

the equlibrium constant can be calculated from the following equation:

K_a = [H⁺][A^-]/[HA]

As in the case of the ion product:

pK_a = -logK_a

Therefore, in obtaining the -log of both sides of the equation describing the dissociation of a weak acid we arrive at the following equation:

-logK_a = -log[H⁺][A^-]/[HA]

Since as indicated above -logK_a = pK_a and taking into account the laws of logrithms:

pK_a = -log[H⁺] -log[A^-]/[HA]

pK_a = pH -log[A^-]/[HA]

From this equation it can be seen that the smaller the pK_a value the stronger is the acid. This is due to the fact that the stronger an acid the more readily it will give up H⁺ and, therefore, the value of [HA] in the above equation will be relatively small.

General structure of amino acids

• All organisms use same 20 amino acids.
• Variation in order of amino acids in polypeptides allow limitless variation.
• All amino acids made up of a chiral carbon attached to 4 different groups      

 - hydrogen
 - amino group
 - carboxyl
 - R group: varies between different amino acids

• Two stereoisomers (mirror images of one another) can exist for each amino acid. Such stereoisomers are called enantiomers. All amino acids found in proteins are in the L configuration.
• Amino acids are zwitterions at physiological pH 7.4. ( i.e. dipolar ions). Some side chains can also be ionized

Structures of the 20 common amino acids

• Side chains of the 20 amino acids vary. Properties of side chains greatly influence overall conformation of protein. E.g. hydrophobic side chains in water-soluble proteins fold into interior of protein
• Some side chains are nonpolar (hydrophobic), others are polar or ionizable at physiological pH (hydrophilic).
• Side chains fall into several chemical classes: aliphatic, aromatic, sulfur-containing, alcohols, bases, acids, and amides. Also catagorized as to hydrophobic vs hydrophilic.
• Must know 3-letter code for each amino acid.

Aliphatic R Groups

• Glycine: least complex structure. Not chiral. Side chain small enough to fit into niches too small for other amino acids.
• Alanine, Valine, Leucine, Isoleucine
  • no reactive functional groups      
  • highly hydrophobic: play important role in maintaining 3-D structures of proteins because of their tendency to cluster away from water
• Proline has cyclic side chain called a pyrolidine ring. Restricts geometry of polypeptides, sometimes introducing abrupt changes in direction of polypeptide chain.

Aromatic R Groups

• Phenylalanine, Tyrosine, Tryptophan
  • Phe has benzene ring therefore hydrophobic.  
  • Tyr and Trp have side chains with polar groups, therefore less hydrophobic than Phe.
  • Absorb UV  280 nm. Therefore used to estimate concentration of proteins.

Sulfur-containing R Groups

• Methionine and Cysteine)
  • Met is hydrophobic. Sulfur atom is nucleophilic.
  • Cys somewhat hydrophobic. Highly reactive. Form disulfide bridges and may stabilize 3-D structure of proteins by cross-linking Cys residues in peptide chains.

Side Chains with Alcohol Groups

• Serine and Threonine
  • have uncharged polar side chains. Alcohol groups give hydrophilic character.
  • weakly ionizable.

Basic R Groups

• Histidine, Lysine, and Arginine.
  • have hydrophilic side chains that are nitrogenous bases and positively charged at physiological pH.
  • Arg is most basic a.a., and contribute positive charges to proteins.

Acidic R Groups and their Amide derivatives

• Aspartate, Glutamate
  • are dicarboxylic acids, ionizable at physiological pH. Confer a negative charge on proteins.
• Asparagine, Glutamine
  • amides of Asp and Glu rspectively
  • highly polar and often found on surface of proteins
  • polar amide groups can form H-bonds with atoms in other amino acids with polar side chains.

MAGNESIUM

The normal serum level of Magnesium is 1.8 to 2.2. mg/dl.

Functions of Magnesium

(a) Irritability of neuromuscular tissues is lowered by Magnesium

(b) Magnesium deficiency leads to decrease in Insulin dependent uptake of glucose

(c) Magnesium supplementation improves glucose tolerance

Causes such as liver cirrhosis, protein calorie malnutrition and hypo para thyroidism leads to hypomagnesemia

The main causes of hypermagnesemia includes renal failure, hyper para thyroidism, rickets, oxalate poisoning and multiple myeloma.

Cholesterol synthesis:

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol synthesis. 

HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different, enzymes in the cytosol.

HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by HMG-CoA Synthase.

HMG-CoA Reductase, the rate-determining step on the pathway for synthesis of cholesterol.

Clinical significance

Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH in the parathyroid gland

Secondary hyperparathyroidism is an appropriately high PTH level seen as a physiological response to hypocalcemia.

A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.