NEET MDS Lessons
Biochemistry
Enzyme Kinetics
Enzymes are protein catalysts that, like all catalysts, speed up the rate of a chemical reaction without being used up in the process. They achieve their effect by temporarily binding to the substrate and, in doing so, lowering the activation energy needed to convert it to a product.
The rate at which an enzyme works is influenced by several factors, e.g.,
- the concentration of substrate molecules (the more of them available, the quicker the enzyme molecules collide and bind with them). The concentration of substrate is designated [S] and is expressed in unit of molarity.
- the temperature. As the temperature rises, molecular motion - and hence collisions between enzyme and substrate - speed up. But as enzymes are proteins, there is an upper limit beyond which the enzyme becomes denatured and ineffective.
- the presence of inhibitors.
- competitive inhibitors are molecules that bind to the same site as the substrate - preventing the substrate from binding as they do so - but are not changed by the enzyme.
- noncompetitive inhibitors are molecules that bind to some other site on the enzyme reducing its catalytic power.
- pH. The conformation of a protein is influenced by pH and as enzyme activity is crucially dependent on its conformation, its activity is likewise affected.
The study of the rate at which an enzyme works is called enzyme kinetics.
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
The pentose phosphate pathway is primarily an anabolic pathway that utilizes the 6 carbons of glucose to generate 5 carbon sugars and reducing equivalents. However, this pathway does oxidize glucose and under certain conditions can completely oxidize glucose to CO2 and water. The primary functions of this pathway are:
- To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.
- To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
- Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates
Enzymes that function primarily in the reductive direction utilize the NADP+/NADPH cofactor pair as co-factors as opposed to oxidative enzymes that utilize the NAD+/NADH cofactor pair. The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis and lactating mammary gland have high levels of the PPP enzymes. In fact 30% of the oxidation of glucose in the liver occurs via the PPP. Additionally, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione. The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source, therefore, any rapidly proliferating cell needs large quantities of NADPH.
Regulation: Glucose-6-phosphate Dehydrogenase is the committed step of the Pentose Phosphate Pathway. This enzyme is regulated by availability of the substrate NADP+. As NADPH is utilized in reductive synthetic pathways, the increasing concentration of NADP+ stimulates the Pentose Phosphate Pathway, to replenish NADPH
- There are two important phospholipids, Phosphatidylcholine and Phosphatidylserine found the cell membrane without which cell cannot function normally.
- Phospholipids are also important for optimal brain health as they found the cell membrane of brain cells also which help them to communicate and influence the receptors function. That is the reason food stuff which is rich in phospholipids like soy, eggs and the brain tissue of animals are good for healthy and smart brain.
- Phospholipids are the main component of cell membrane or plasma membrane. The bilayer of phospholipid molecules determine the transition of minerals, nutrients, and drugs in and out of the cell and affect various functions of them.
- As phospholipids are main component of all cell membrane, they influence a number of organs and tissues, such as the heart, blood cells and the immune system. As we grown up the amount of phospholipids decreases and reaches to decline.
- Phospholipids present in cell membrane provide cell permeability and flexibility with various substances as well its ability to move fluently. The arrangement of phospholipid molecules in lipid bilayer prevent amino acids, carbohydrates, nucleic acids, and proteins from moving across the membrane by diffusion. The lipid bi-layer is usually help to prevent adjacent molecules from sticking to each other.
- The selectivity of cell membrane form certain substances are due to the presence of hydrophobic and hydrophilic part molecules and their arrangement in bilayer. This bilayer is also maintained the normal pH of cell to keeps it functioning properly.
- Phospholipids are also useful in the treatment of memory problem associated with chronic substances as they improve the ability of organism to adapt the chronic stress.
Amino acids
Proteins are linear polymers of amino acids. Participate in virtually every biological process. Perform diverse functions:
1. Enzymes: catalyze all reactions in living organisms
2. Storage and transport
3. Structural
4. Mechanical work ( flagella, muscles, separation of chromosomes)
5. Decoding information (translation, transcription, DNA replication)
6. Cell-signalling (hormones and receptors)
7. Defence (antibodies)
IONIZATION OF WATER, WEAK ACIDS AND WEAK BASES
The ionization of water can be described by an equilibrium constant. When weak acids or weak bases are dissolved in water, they can contribute H+ by ionizing (if acids) or consume H+ by being protonated (if bases). These processes are also governed by equilibrium constants
Water molecules have a slight tendency to undergo reversible ionization to yield a hydrogen ion and a hydroxide ion :
H2O = H+ + OH−
The position of equilibrium of any chemical reaction is given by its equilibrium constant. For the general reaction,
A+B = C + D
STEROIDS
Steroids are the compounds containing a cyclic steroid nucleus (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene nucleus (rings A, B and C) to which a cyclopentane ring (D) is attached.
Steroids are the compounds containing a cyclic steroid nucleus (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene nucleus (rings A, B and C) to which a cyclopentane ring (D) is attached.
There are several steroids in the biological system. These include cholesterol, bile acids, vitamin D, sex hormones, adrenocortical hormones,sitosterols, cardiac glycosides and alkaloids
Glycolysis Pathway
The reactions of Glycolysis take place in the cytosol of cells.
Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate. Initially, there is energy input corresponding to cleavage of two ~P bonds of ATP.
1. Hexokinase catalyzes: glucose + ATP → glucose-6-phosphate + ADP
ATP binds to the enzyme as a complex with Mg++.
The reaction catalyzed by Hexokinase is highly spontaneous
2. Phosphoglucose Isomerase catalyzes:
glucose-6-phosphate (aldose) → fructose-6-phosphate (ketose)
The Phosphoglucose Isomerase mechanism involves acid/base catalysis, with ring opening, isomerization via an enediolate intermediate, and then ring closure .
3. Phosphofructokinase catalyzes:
fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP
The Phosphofructokinase reaction is the rate-limiting step of Glycolysis. The enzyme is highly regulated.
4. Aldolase catalyzes:
fructose-1,6-bisphosphate → dihydroxyacetone phosphate + glyceraldehyde-3-phosphate
The Aldolase reaction is an aldol cleavage, the reverse of an aldol condensation.
5. Triose Phosphate Isomerase (TIM) catalyzes
dihydroxyacetone phosphate (ketose) → glyceraldehyde-3-phosphate (aldose)
Glycolysis continues from glyceraldehydes-3-phosphate
The equilibrium constant (Keq) for the TIM reaction favors dihydroxyacetone phosphate, but removal of glyceraldehyde-3-phosphate by a subsequent spontaneous reaction allows throughput.
6. Glyceraldehyde-3-phosphate Dehydrogenase catalyzes:
glyceraldehyde-3-phosphate + NAD+ + Pi → 1,3,bisphosphoglycerate + NADH + H+
This is the only step in Glycolysis in which NAD+ is reduced to NADH
A cysteine thiol at the active site of Glyceraldehyde-3-phosphate Dehydrogenase has a role in catalysis .
7. Phosphoglycerate Kinase catalyzes:
1,3-bisphosphoglycerate + ADP → 3-phosphoglycerate + ATP
This transfer of phosphate to ADP, from the carboxyl group on 1,3-bisphosphoglycerate, is reversible
8. Phosphoglycerate Mutase catalyzes: 3-phosphoglycerate → 2-phosphoglycerate
Phosphate is shifted from the hydroxyl on C3 of 3-phosphoglycerate to the hydroxyl on C2.
9. Enolase catalyzes: 2-phosphoglycerate → phosphoenolpyruvate + H2O
This Mg++-dependent dehydration reaction is inhibited by fluoride. Fluorophosphate forms a complex with Mg++ at the active site .
10. Pyruvate Kinase catalyzes: phosphoenolpyruvate + ADP → pyruvate + ATP
This transfer of phosphate from PEP to ADP is spontaneous.
Balance sheet for high energy bonds of ATP:
- 2 ATP expended
- 4 ATP produced (2 from each of two 3C fragments from glucose)
- Net Production of 2~ P bonds of ATP per glucose