SELENIUM

normal serum level is 50-100 mg/day

Selenium dependent enzymes include glutathione Peroxidase and 5-de-iodinase. Selenium concentration in testis is the highest in adult.  It is very necessary for normal development and maturation of sperm.

Glycolysis enzymes are located in the cytosol of cells.  Pyruvate enters the mitochondrion to be metabolized further

Mitochondrial compartments: The mitochondrial matrix contains Pyruvate Dehydrogenase and enzymes of Krebs Cycle, plus other pathways such as fatty acid oxidation. 

Pyruvate Dehydrogenase catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA

FAD (Flavin Adenine Dinucleotide) is a derivative of the B-vitamin riboflavin (dimethylisoalloxazine-ribitol). The flavin ring system undergoes oxidation/reduction as shown below. Whereas NAD⁺ is a coenzyme that reversibly binds to enzymes, FAD is a prosthetic group, that is permanently part of the complex. 

FAD accepts and donates 2 electrons with 2 protons (2 H):

Thiamine pyrophosphate (TPP) is a derivative of  thiamine (vitamin B₁). Nutritional deficiency of thiamine leads to the disease beriberi. Beriberi affects especially the brain, because TPP is required for carbohydrate metabolism, and the brain depends on glucose metabolism for energy

Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism. The "high energy" thioester linkage makes it an excellent donor of the acetate moiety

For example, acetyl CoA functions as:

• input to the Krebs Cycle, where the acetate moiety is further degraded to CO₂.
• donor of acetate for synthesis of fatty acids, ketone bodies, and cholesterol.

ATPs  formed in TCA cycle from one molecule of Pyruvate

1. 3ATP            7. 3ATP          5. 3 ATP                     

 8. 1 ATP         9. 2 ATP          11.3 ATP         Total =15 ATP.

 ATPS formed from one molecule of Acetyl CoA =12ATP

ATPs formed from one molecule of glucose after complete oxidation

One molecule of glucose -->2 molecules of pyruvate

['By glycolysis] ->8 ATP

2 molecules of pyruvate [By TCA cycle] -> 30 ATP

Total = 38 ATP

Glycogen Metabolism

The formation of glycogen from glucose is called Glycogenesis

Glycogen is a polymer of glucose residues linked mainly by a(1→ 4)  glycosidic linkages. There are a(1→6) linkages at branch points. The chains and branches are longer than shown. Glucose is stored as glycogen predominantly in liver and muscle cells

Glycogen Synthesis

Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis. As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for synthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.

UDP-glucose is formed from glucose-1-phosphate and uridine triphosphate (UTP)

glucose-1-phosphate + UTP → UDP-glucose + 2 P_i

Cleavage of PPi is the only energy cost for glycogen synthesis (1P bond per glucose residue)

Glycogenin initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes glycosylation of one of its own tyrosine residues.

Physiological regulation of glycogen metabolism

Both synthesis and breakdown of glycogen are spontaneous. If glycogen synthesis and phosphorolysis were active simultaneously in a cell, there would be a futile cycle with cleavage of 1 P bond per cycle

To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated, both by allosteric effectors and by covalent modification (phosphorylation)

Glycogen catabolism (breakdown)

Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the →(1→4) glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product.

Glycogen (n residues) + P_i → glycogen (n-1 residues) + glucose-1-phosphate

The Major product of glycogen breakdown is glucose -1-phosphate

Fate of glucose-1-phosphate in relation to other pathways:

Phosphoglucomutase catalyzes the reversible reaction:

Glucose-1-phosphate → Glucose-6-phosphate

VITAMIN C: ASCORBIC ACID, ASCORBATE

Vitamin C benefits the body by holding cells together through collagen synthesis; collagen is a connective tissue that holds muscles, bones, and other tissues together. Vitamin C also aids in wound healing, bone and tooth formation, strengthening blood vessel walls, improving immune system function, increasing absorption and utilization of iron, and acting as an antioxidant.

RDA The Recommended Dietary Allowance (RDA) for Vitamin C is 90 mg/day for adult males and 75 mg/day for adult females

Vitamin C Deficiency

Severe vitamin C deficiency result in the disease known as scurvy, causing a loss of collagen strength throughout the body. Loss of collagen results in loose teeth, bleeding and swollen gums, and improper wound healing.

3-D Structure of proteins

Proteins are the main players in the life of a cell. Each protein is a unique sequence of amino acid residues, each of which folds into a unique, stable, three dimentional structure that is biologically functional.

Conformation = spatial arrangement of atoms that depends on rotation of bonds. Can change without breaking covalent bonds.

• Since each residue has a number of possible conformations, and there are many residues in a protein, the number of possible conformations for a protein is enormous.

Native conformation = single, stable shape a protein assumes under physiological conditions.

• In native conformation, rotation around covalent bonds in polypeptide is constrained by a number of factors ( H-bonding, weak interactions, steric interference)
• Biological function of proteins depends completely on its conformation. In biology, shape is everything.
• Proteins can be classified as globular or fibrous.

There are 4 levels of protein structure

• Primary structure
  • linear sequence of amino acids
  • held by covalent forces
  • primary structure determines all oversall shape of folded polypeptides (i.e primary structure determines secondary , tertiary, and quaternary structures)
• Secondary structure
  • regions of regularly repeating conformations of the peptide chain (α helices, β sheets)
  • maintained by H-bonds between amide hydrogens and carbonyl oxygens of peptide backbone.
• Tertiary structure
  • completely folded and compacted polypeptide chain.
  • stabilized by interactions of sidechains of non-neighboring amino acid residues (fibrous proteins lack tertiary structure)
• Quaternary structure
  • association of two or more polypeptide chains into a multisubunit protein.

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.