NEET MDS Lessons
Biochemistry
Clinical significance
Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH in the parathyroid gland
Secondary hyperparathyroidism is an appropriately high PTH level seen as a physiological response to hypocalcemia.
A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.
The Bicarbonate Buffer System
This is the main extracellular buffer system which (also) provides a means for the necessary removal of the CO2 produced by tissue metabolism. The bicarbonate buffer system is the main buffer in blood plasma and consists of carbonic acid as proton donor and bicarbonate as proton acceptor :
H2CO3 = H+ + HCO3–
If there is a change in the ratio in favour of H2CO3, acidosis results.
This change can result from a decrease in [HCO3 − ] or from an increase in [H2CO3 ]
Most common forms of acidosis are metabolic or respiratory
Metabolic acidosis is caused by a decrease in [HCO3 − ] and occurs, for example, in uncontrolled diabetes with ketosis or as a result of starvation.
Respiratory acidosis is brought about when there is an obstruction to respiration (emphysema, asthma or pneumonia) or depression of respiration (toxic doses of morphine or other respiratory depressants)
Alkalosis results when [HCO3 − ] becomes favoured in the bicarbonate/carbonic acid ratio
Metabolic alkalosis occurs when the HCO3 − fraction increases with little or no concomitant change in H2CO3
Severe vomiting (loss of H+ as HCl) or ingestion of excessive amounts of sodium bicarbonate (bicarbonate of soda) can produce this condition
Respiratory alkalosis is induced by hyperventilation because an excessive removal of CO2 from the blood results in a decrease in [H2CO3 ]
Alkalosis can produce convulsive seizures in children and tetany, hysteria, prolonged hot baths or lack of O2 as high altitudes.
The pH of blood is maintained at 7.4 when the buffer ratio [HCO3 − ] / [ H2CO3] becomes 20
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.
Glucagon
Glucagon, a peptide hormone synthesized and secreted from the α-cells of the islets of Langerhans of pancreas, raises blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. Glucagon and insulin are part of a feedback system that keeps blood glucose levels at a stable level.
Regulation and function
Secretion of glucagon is stimulated by hypoglycemia, epinephrine, arginine, alanine, acetylcholine, and cholecystokinin.
Secretion of glucagon is inhibited by somatostatin, insulin, increased free fatty acids and keto acids into the blood, and increased urea production.
TRIGLYCEROL
Triacylglycerols (formerly triglycerides) are the esters of glycerol with fatty acids. The fats and oils that are widely distributed in both plants and animals are chemically triacylglycerols.
They are insoluble in water and non-polar in character and commonly known as neutral fats.
Triacylglycerols are the most abundant dietary lipids. They are the form in which we store reduced carbon for energy. Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids. Most triacylglycerols are "mixed." The three fatty acids differ in chain length and number of double bonds
Structures of acylglycerols :
Monoacylglycerols, diacylglycerols and triacylglycerols, respectively consisting of one, two and three molecules of fatty acids esterified to
a molecule of glycerol
Lipases hydrolyze triacylglycerols, releasing one fatty acid at a time, producing diacylglycerols, and eventually glycerol
Glycerol arising from hydrolysis of triacylglycerols is converted to the Glycolysis intermediate dihydroxyacetone phosphate, by reactions catalyzed by:
(1) Glycerol Kinase
(2) Glycerol Phosphate Dehydrogenase
Free fatty acids, which in solution have detergent properties, are transported in the blood bound to albumin, a serum protein produced by the liver.
Several proteins have been identified that facilitate transport of long chain fatty acids into cells, including the plasma membrane protein CD36
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.
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