PHOSPHORUS

Serum level of phosphate is 3-4 mg/dl for adults and 5-6 mg/dl in children. Consumption of calcitriol increases phosphate absorption.

Functions of phosphorus
(a) Plays key role in formation of tooth and bone

(b) Production of high energy phosphate compounds such as ATP, CTP, GTP etc.,

(c) Synthesis of nucleotide co-enzymes such as NAD and NADP

(d) Formation of phosphodiester backbone structure for DNA and RNA synthesis

Hypophosphatemia is the condition which leads to decrease in absorption of phosphorus. it leads to hypercalcamia

Hyperphosphatemia, increase in absorption of phosphate was noticed. Hyperphosphatemia leads to cell lysis, hypocalcemia and thyrotoxicosis.

Proteins are complex macromolecules composed of amino acids that perform diverse biological functions. Understanding their structure-function relationships is crucial for medical applications and biochemistry.

Levels of Protein Structure

Primary Structure

• Linear sequence of amino acids connected by peptide bonds
• Determines all higher levels of organization
• Coded by DNA sequence

Secondary Structure

• Local folding patterns stabilized by hydrogen bonds
• Alpha helix: Right-handed spiral structure
• Beta sheet: Extended polypeptide chains arranged side by side
• Beta turn: Connects different secondary structural elements

Tertiary Structure

• Three-dimensional folding of entire polypeptide chain
• Stabilized by:
  • Hydrogen bonds
  • Disulfide bridges
  • Van der Waals forces
  • Electrostatic interactions
  • Hydrophobic interactions

Quaternary Structure

• Assembly of multiple polypeptide subunits
• Present only in proteins with more than one polypeptide chain
• Examples: Hemoglobin (4 subunits), antibodies

Protein Classification

Based on Structure

1. Fibrous Proteins

   • Elongated, insoluble
   • Structural functions
   • Examples: Collagen, keratin, elastin

2. Globular Proteins

   • Compact, soluble
   • Functional proteins
   • Examples: Enzymes, antibodies, hormones

Based on Composition

1. Simple Proteins

   • Composed only of amino acids
   • Examples: Albumin, globulins

2. Conjugated Proteins

   • Contain non-protein prosthetic groups
   • Glycoproteins: Contain carbohydrates
   • Lipoproteins: Contain lipids
   • Nucleoproteins: Contain nucleic acids
   • Phosphoproteins: Contain phosphate groups
   • Metalloproteins: Contain metal ions

Sugar derivatives

Sugar alcohol - lacks an aldehyde or ketone. An example is ribitol.

Sugar acid - the aldehyde at C1, or the hydroxyl on the terminal carbon, is oxidized to a carboxylic acid. Examples are gluconic acid and glucuronic acid

Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated.

N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH.

Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.

R-OH + HO-R'   → R-O-R' + H₂O

Disaccharides: Maltose, a cleavage product of starch, is a disaccharide with an α (1→4) glycosidic linkage between the C1 hydroxyl of one glucose and the C4 hydroxyl of a second glucose. Maltose is the α anomer, because the O at C1  points down from the ring.

Cellobiose, a product of cellulose breakdown, is the otherwise equivalent β anomer.  The configuration at the anomeric C1 is β (O points up from the ring). The β(1→4) glycosidic linkage is represented as a "zig-zag" line, but one glucose residue is actually flipped over relative to the other.

Other disaccharides

• Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose and fructose. Because the configuration at the anomeric carbon of glucose is α (O points down from the ring), the linkage is designated α (1→2). The full name is α -D-glucopyranosyl-(1→2) β -D- fructopyranose.
• Lactose, milk sugar, is composed of glucose and galactose with β (→4) linkage → the anomeric hydroxyl of galactose. Its full name is β -D-galactopyranosyl-(1→)- α -D-glucopyranose

Polysaccharides:

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects

Amylose is a glucose polymer with α (1→4) glycosidic linkages, as represented above. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end

Amylopectin is a glucose polymer with mainly α (1→4) linkages, but it also has branches formed by α (1→6) linkages. The branches are generally longer than shown above. The branches produce a compact structure, and provide multiple chain ends at which enzymatic cleavage of the polymer can occur. 

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α (1→6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose, with β (1→4) linkages. Every other glucose in cellulose is flipped over, due to the β linkages. This promotes intrachain and interchain hydrogen bonds, as well as van der Waals interactions, that cause cellulose chains to be straight and rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.

Glycosaminoglycans (mucopolysaccharides) are polymers of repeating disaccharides. Within the disaccharides, the sugars tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1→3) and β(1→4).

When covalently linked to specific core proteins, glycosaminoglycans form complexes called proteoglycans. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules. For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues.

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to a sulfated sugar called iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated

Heparin, a glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated.

Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling and adhesion at the cell surface have been identified that recognize and bind segments of heparan sulfate chains having particular patterns of sulfation

Lectins are glycoproteins that recognize and bind to specific oligosaccharides.

• Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools
• Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting phagocytosis of these organisms as part of the immune response.
• Selectins are integral proteins of the plasma membrane with lectin-like domains that protrude on the outer surface of mammalian cells. Selectins participate in cell-cell recognition and binding.

These amino acids have aromatic side chains, which contribute to protein structure, UV absorbance, and biochemical signaling.

1. Phenylalanine (Phe, F)

• Structure: Contains a benzyl side chain (a phenyl group attached to a CH₂).

• Properties: Non-polar, hydrophobic.

• Function: Precursor to tyrosine, dopamine, norepinephrine, and epinephrine.

2. Tyrosine (Tyr, Y)

• Structure: Similar to phenylalanine but with a hydroxyl group (-OH) on the aromatic ring.

• Properties: Polar, can participate in hydrogen bonding.

• Function: Precursor to catecholamines and thyroid hormones; involved in signal transduction via phosphorylation.

3. Tryptophan (Trp, W)

• Structure: Contains an indole ring (a fused double ring with nitrogen).

• Properties: Slightly polar, bulky.

• Function: Precursor to serotonin, melatonin, and niacin; absorbs UV light strongly at 280 nm.

4. Histidine (His, H) (sometimes included due to its aromatic-like imidazole ring)

• Structure: Has an imidazole ring (five-membered ring with two nitrogen atoms).

• Properties: Polar, positively charged at physiological pH.

• Function: Key role in enzyme active sites; acts as a proton donor/acceptor.

Bonus Insight: UV Absorbance

• Tryptophan and Tyrosine absorb UV light at ~280 nm, which is useful for measuring protein concentration.

• Phenylalanine absorbs weakly at ~260 nm.

FACTORS AFFECTING ENZYME ACTIVITY

Velocity or rate of enzymatic reaction is assessed by the rate of change in concentration of substrate or product at a given time duration. Various factors which affect the activity of enzymes include:

1. Substrate concentration

2. Enzyme concentration

3. Product concentration

4. Temperature 5. Hydrogen ion concentration (pH)

6. Presence of activators

7. Presence of inhibitor

Effect of substrate Concentration :  Reaction velocity of an enzymatic process increases with constant enzyme concentration and increase in substrate concentration.

Effect of enzyme Concentration: As there is optimal substrate concentration, rate of an enzymatic reaction or velocity (V) is directly proportional to the enzyme concentration.

Effect of product concentration In case of a reversible reaction catalyzed by a enzyme, as per the law of mass action the rate of reaction is slowed down with equilibrium. So, rate of reaction is slowed, stopped or even reversed with increase in product concentration

Effect of temperature: Velocity of enzymatic reaction increases with temperature of the medium which they are most efficient and the same is termed as optimum temperature.

Effect of pH: Many enzymes are most efficient in the region of pH 6-7, which is the pH of the cell. Outside this range, enzyme activity drops off very rapidly. Reduction in efficiency caused by changes in the pH is due to changes in the degree of ionization of the substrate and enzyme.

Highly acidic or alkaline conditions bring about a denaturation and subsequent loss of enzymatic activity

Exceptions such as pepsin (with optimum pH 1-2), alkaline phosphatase (with optimum pH 9-10) and acid phosphatase (with optimum pH 4-5)

Presence of activators Presence of certain inorganic ions increases the activity of enzymes. The best examples are chloride ions activated salivary amylase and calcium activated lipases.

Effect of Inhibitors The catalytic enzymatic reaction may be inhibited by substances which prevent the formation of a normal enzyme-substrate complex. The level of inhibition then depends entirely upon the relative concentrations of the true substrate and the inhibitor

Role of Coenzymes

The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another.

Ex. The hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD;

The amine (-NH2) carried by pyridoxal phosphate