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.

The Protein Buffer Systems

The protein buffers are very important in the plasma and the intracellular fluids but their concentration is very low in cerebrospinal fluid, lymph and interstitial fluids.

The proteins exist as anions serving as conjugate bases (Pr ⁻ ) at the blood pH 7.4 and form conjugate acids (HPr) accepting H⁺ .  They have the capacity to buffer some H₂CO₃  in the blood.

Carbohydrates (glycans) have the  basic composition

• Monosaccharides - simple sugars,  with multiple hydroxyl groups. Based on the number of carbons (e.g., 3, 4, 5, or 6) a monosaccharide is a triose, tetrose, pentose, or hexose, etc.
• Disaccharides - two monosaccharides covalently linked
• Oligosaccharides - a few monosaccharides covalently linked.
• Polysaccharides - polymers consisting of chains of monosaccharide or disaccharide units

LIPIDS

The lipids are a heterogeneous group of compounds, including fats, oils, steroids, waxes, and related compounds, which are related more by their physical than by their chemical properties.

Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents.

Most membrane lipids are amphipathic, having a non-polar end and a polar end

Lipids are important in biological systems because they form the cell membrane, a mechanical barrier that divides a cell from the external environment.

Lipids also provide energy for life and several essential vitamins are lipids.

Lipids can be divided in two major classes, nonsaponifiable lipids and saponifiable lipids.

A nonsaponifiable lipid cannot be broken up into smaller molecules by hydrolysis, which includes triglycerides, waxes, phospholipids, and sphingolipids.

A saponifiable lipid contains one or more ester groups allowing it to undergo hydrolysis in the presence of an acid, base, or enzyme.

Nonsaponifiable lipids include steroids, prostaglandins, and terpenes

Nonpolar lipids, such as triglycerides, are used for energy storage and fuel.

Polar lipids, which can form a barrier with an external water environment, are used in membranes.

Polar lipids include glycerophospholipids and sphingolipids.

Fatty acids are important components of all of these lipids.

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.

Regulation of PTH secretion

Secretion of parathyroid hormone is controlled chiefly by serum [Ca²⁺] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca²⁺] is low.

Hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.

Hypermagnesemia also results in inhibition of PTH secretion.

Stimulators of PTH includes decreased serum [Ca²⁺], mild decreases in serum [Mg²⁺], and an increase in serum phosphate.

Inhibitors include increased serum [Ca²⁺], severe decreases in serum [Mg²⁺], which also produces symptoms of hypoparathyroidism (such as hypocalcemia), and calcitriol.