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Biochemistry - NEETMDS- courses
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Biochemistry

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.

Nomenclature for stereoisomers: D and L designations are based on the configuration about the single asymmetric carbon in glyceraldehydes

 

For sugars with more than one chiral center, the D or L designation refers to the asymmetric carbon farthest from the aldehyde or keto group.

Most naturally occurring sugars are D isomers.

D & L sugars are mirror images of one another. They have the same name. For example, D-glucose and L-glucose

Other stereoisomers have unique names, e.g., glucose, mannose, galactose, etc. The number of stereoisomers is 2 n, where n is the number of asymmetric centers. The six-carbon aldoses have 4 asymmetric centers, and thus 16 stereoisomers (8 D-sugars and 8 L-sugars

An aldehyde can react with an alcohol to form a hemiacetal

Similarly a ketone can react with an alcohol to form a hemiketal

 

Pentoses and hexoses can cyclize, as the aldehyde or keto group reacts with a hydroxyl on one of the distal carbons

E.g., glucose forms an intra-molecular hemiacetal by reaction of the aldehyde on C1 with the hydroxyl on C5, forming a six-member pyranose ring, named after the compound pyran

The representations of the cyclic sugars below are called Haworth projections.

 

 

Fructose can form either: 

  • a six-member pyranose ring, by reaction of the C2 keto group with the hydroxyl on C6
  • a 5-member furanose ring, by reaction of the C2 keto group with the hydroxyl on C5.

 

 

Cyclization of glucose produces a new asymmetric center at C1, with the two stereoisomers called anomers, α & β

 

Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1 extending either:

  • below the ring (α)
  • above the ring (β).

Because of the tetrahedral nature of carbon bonds, the cyclic form of pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar

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

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.

The pH scale

An acidic solution is one in which [H+ ] > [OH- ]

•In an acidic solution, [H+ ] > 10-7 , pH < 7.

•A basic solution is when [OH- ] > [H+ ].

•In a basic solution, [OH- ] > 10-7 , pOH < 7, and pH >7.

• When the pH = 7, the solution is neutral.

•Physiological pH range is 6.5 to 8.0

 

FAT-SOLUBLE VITAMINS

The fat-soluble vitamins, A, D, E, and K, are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess than water-soluble vitamins.

VITAMIN A: RETINOL

 Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division, gene expression, and regulation of the immune system.

The skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers.

One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene. The Recommended Dietary Allowance (RDA) for vitamin A is 900 mcg/ day for adult males and 700 mcg/ day for adult females.

Vitamin A Deficiency

Vitamin A deficiency is rare, but the disease that results is known as xerophthalmia.

Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth.

Vitamin A toxicity The Tolerable Upper Intake Level (UL) for adults is 3,000 mcg RAE.

VITAMIN D

Vitamin D plays a critical role in the body’s use of calcium and phosphorous. It works by increasing the amount of calcium absorbed from the small intestine, helping to form and maintain bones.

Vitamin D benefits the body by playing a role in immunity and controlling cell growth. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth.

RDA  From 12 months to age fifty, the RDA is set at 15 mcg.

20 mcg of cholecalciferol equals 800 International Units (IU), which is the recommendation for maintenance of healthy bone for adults over fifty.

Vitamin D Deficiency

Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults may result in osteomalacia (muscle and bone weakness), and osteoporosis (loss of bone mass).

Vitamin D toxicity

The Tolerable Upper Intake Level (UL) for vitamin D is set at 100 mcg for people 9 years of age and older. High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning.

VITAMIN E: TOCOPHEROL

Vitamin E benefits the body by acting as an antioxidant, and protecting vitamins A and C, red blood cells, and essential fatty acids from destruction.

RDA  One milligram of alpha-tocopherol equals to 1.5 International Units (IU). RDA guidelines state that males and females over the age of 14 should receive 15 mcg of alpha-tocopherol per day.

Vitamin E Deficiency Vitamin E deficiency is rare. Cases of vitamin E deficiency usually only occur in premature infants and in those unable to absorb fats.

 

VITAMIN K

Vitamin K is naturally produced by the bacteria in the intestines, and plays an essential role in normal blood clotting, promoting bone health, and helping to produce proteins for blood, bones, and kidneys.

RDA

Males and females age 14 - 18: 75 mcg/day; Males and females age 19 and older: 90 mcg/day

Vitamin K Deficiency

Hemorrhage can occur due to sufficient amounts of vitamin K.

Vitamin K deficiency may appear in infants or in people who take anticoagulants, such as Coumadin (warfarin), or antibiotic drugs.

Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week.

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 = Ka. 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:

Ka = [H+][A-]/[HA]

As in the case of the ion product:

pKa = -logKa

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

-logKa = -log[H+][A-]/[HA]

 

Since as indicated above -logKa = pKa and taking into account the laws of logrithms:

 

pKa = -log[H+] -log[A-]/[HA]

pKa = pH -log[A-]/[HA]

From this equation it can be seen that the smaller the pKa 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.

 

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