NEET MDS Lessons
Biochemistry
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.
Applications of the Henderson-Hasselbalch equation
• Calculate the ratio of CB to WA, if pH is given
• Calculate the pH, if ratio of CB to WA is known
• Calculate the pH of a weak acid solution of known concentration
• Determine the pKa of a WA-CB pair
• Calculate change in pH when strong base is added to a solution of weak acid. This is represented in a titration curve
• Calculate the pI
CLINICAL SIGNIFICANCE OF ENZYMES
The measurement of enzymes level in serum is applied in diagnostic application
Pancreatic Enzymes
Acute pancreatitis is an inflammatory process where auto digestion of gland was noticed with activation of the certain pancreatic enzymes. Enzymes which involves in pancreatic destruction includes α-amylase, lipase etc.,
1. α-amylase (AMYs) are calcium dependent hydrolyase class of metaloenzyme that catalyzes the hydrolysis of 1, 4- α-glycosidic linkages in polysaccharides. The normal values of amylase is in range of 28-100 U/L. Marked increase of 5 to 10 times the upper reference limit (URL) in AMYs activity indicates acute pancreatitis and severe glomerular impairment.
2. Lipase is single chain glycoprotein. Bile salts and a cofactor called colipase are required for full catalytic activity of lipase. Colipase is secreted by pancreas. Increase in plasma lipase activity indicates acute pancreatitis and carcinoma of the pancreas.
Liver Enzymes
Markers of Hepatocellular Damage
1. Aspartate transaminase (AST) Aspartate transaminase is present in high concentrations in cells of cardiac and skeletal muscle, liver, kidney and erythrocytes. Damage to any of these tissues may increase plasma AST levels.
The normal value of AST for male is <35 U/ L and for female it is <31 U/L.
2. Alanine transaminase (ALT) Alanine transaminase is present at high concentrations in liver and to a lesser extent, in skeletal muscle, kidney and heart. Thus in case of liver damage increase in both AST and ALT were noticed. While in myocardial infarction AST is increased with little or no increase in ALT.
The normal value of ALT is <45 U/L and <34 U/L for male and female respectively
Markers of cholestasis
1. Alkaline phosphatases
Alkaline phosphatases are a group of enzymes that hydrolyse organic phosphates at high pH. They are present in osteoblasts of bone, the cells of the hepatobiliary tract, intestinal wall, renal tubules and placenta.
Gamma-glutamyl-transferase (GGT) Gamma-glutamyl-transferase catalyzes the transfere of the γ–glutamyl group from peptides. The activity of GGT is higher in men than in women. In male the normal value of GGT activity is <55 U/L and for female it is <38 U/L.
2. Glutamate dehydrogenase (GLD) Glutamate dehydrogenase is a mitochondrial enzyme found in liver, heart muscle and kidneys.
Muscle Enzymes
1. Creatine Kinase Creatine kinase (CK) is most abundant in cells of brain, cardiac and skeletal.
2. Lactate Dehydrogenase
Lactate dehydrogenase (LD) catalyses the reversible interconversion of lactate and pyruvate.
Cholesterol synthesis:
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol synthesis.
HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different, enzymes in the cytosol.
HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by HMG-CoA Synthase.
HMG-CoA Reductase, the rate-determining step on the pathway for synthesis of cholesterol.
CALCIUM
Total calcium in the human body is 1 to 1.5kg, out of which 99% is seen in bone and 1% in extracellular fluid. The main source of calcium is milk.
The daily requirement of calcium for child is 1200mg/day and for adult it is 500mg/day. During pregnancy /lactation the calcium requirement is 1500mg/day.
The absorption of calcium takes place in 1st and 2nd part of deuodenum. Calcium absorption requires carrier protein, helped by Ca2+ - dependent ATpase.
Factors responsible for increase in calcium absorption include Vitamin D, Parathyroid hormone, acidity and amino acids. Factors such as phytic acid,oxalates, malabsorption syndromes and Phosphates decreases calcium absorption. The normal calcium level in blood is 9-11mg/dl.
Ampholytes, Polyampholytes, pI and Zwitterion
Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.
For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH2 group:
pI = [pKa-(COOH) + pKa-(NH3+)]/2
For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.
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.