NEET MDS Lessons
Biochemistry
CHOLESTEROL AND ITS IMPORTANCE
Cholesterol is an important lipid found in the cell membrane. It is a sterol, which means that cholesterol is a combination of a steroid and an alcohol .
It is an important component of cell membranes and is also the basis for the synthesis of other steroids, including the sex hormones estradiol and testosterone, as well as other steroids such as cortisone and vitamin D.
In the cell membrane, the steroid ring structure of cholesterol provides a rigid hydrophobic structure that helps boost the rigidity of the cell membrane.
Without cholesterol the cell membrane would be too fluid. In the human body, cholesterol is synthesized in the liver.
Cholesterol is insoluble in the blood, so when it is released into the blood stream it forms complexes with lipoproteins.
Cholesterol can bind to two types of lipoprotein, called high-density lipoprotein (HDL) and low-density lipoprotein (LDL).
A lipoprotein is a spherical molecule with water soluble proteins on the exterior. Therefore, when cholesterol is bound to a lipoprotein, it becomes blood soluble and can be transported throughout the body.
HDL cholesterol is transported back to the liver. If HDL levels are low, then the blood level of cholesterol will increase.
High levels of blood cholesterol are associated with plaque formation in the arteries, which can lead to heart disease and stroke.
The Protein Buffer Systems
The protein buffers are very important in the plasma and the intracellular fluids but their concentration is very low in cerebrospinal fluid, lymph and interstitial fluids.
The proteins exist as anions serving as conjugate bases (Pr − ) at the blood pH 7.4 and form conjugate acids (HPr) accepting H+ . They have the capacity to buffer some H2CO3 in the blood.
The Effects of Enzyme Inhibitors
Enzymes can be inhibited
- competitively, when the substrate and inhibitor compete for binding to the same active site or
- noncompetitively, when the inhibitor binds somewhere else on the enzyme molecule reducing its efficiency.
The distinction can be determined by plotting enzyme activity with and without the inhibitor present.
Competitive Inhibition
In the presence of a competitive inhibitor, it takes a higher substrate concentration to achieve the same velocities that were reached in its absence. So while Vmax can still be reached if sufficient substrate is available, one-half Vmax requires a higher [S] than before and thus Km is larger.
Noncompetitive Inhibition
With noncompetitive inhibition, enzyme molecules that have been bound by the inhibitor are taken out
- enzyme rate (velocity) is reduced for all values of [S], including
- Vmax and one-half Vmax but
- Km remains unchanged because the active site of those enzyme molecules that have not been inhibited is unchanged.
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.
ESSENTIAL FATTY ACIDS (EFAs) Polyunsaturated FAs,such as Linoleic acid and g(gamma)- Linolenic acid, are ESSENTIAL FATTY ACIDS — we cannot make them, and we need them, so we must get them in our diets mostly from plant sources.
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.
Insulin
Insulin is a polypeptide hormone synthesized in the pancreas by β-cells, which construct a single chain molecule called proinsulin.
Insulin, secreted by the β-cells of the pancreas in response to rising blood glucose levels, is a signal that glucose is abundant.
Insulin binds to a specific receptor on the cell surface and exerts its metabolic effect by a signaling pathway that involves a receptor tyrosine kinase phosphorylation cascade.
The pancreas secretes insulin or glucagon in response to changes in blood glucose.
Each cell type of the islets produces a single hormone: α-cells produce glucagon; β-cells, insulin; and δ-cells, somatostatin.
Insulin secretion
When blood glucose rises, GLUT2 transporters carry glucose into the b-cells, where it is immediately converted to glucose 6-phosphate by hexokinase IV (glucokinase) and enters glycolysis. The increased rate of glucose catabolism raises [ATP], causing the closing of ATP-gated K+ channels in the plasma membrane. Reduced efflux of K+ depolarizes the membrane, thereby opening voltage-sensitive Ca2+ channels in the plasma membrane. The resulting influx of Ca2+ triggers the release of insulin by exocytosis.
Insulin lowers blood glucose by stimulating glucose uptake by the tissues; the reduced blood glucose is detected by the β-cell as a diminished flux through the hexokinase reaction; this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.
Insulin counters high blood glucose
Insulin stimulates glucose uptake by muscle and adipose tissue, where the glucose is converted to glucose 6-phosphate. In the liver, insulin also activates glycogen synthase and inactivates glycogen phosphorylase, so that much of the glucose 6-phosphate is channelled into glycogen.
Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease. There are two major clinical classes of diabetes mellitus: type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. In type I diabetes, the disease begins early in life and quickly becomes severe. IDDM requires insulin therapy and careful, lifelong control of the balance between dietary intake and insulin dose.
Characteristic symptoms of type I (and type II) diabetes are excessive thirst and frequent urination (polyuria), leading to the intake of large volumes of water (polydipsia)
Type II diabetes is slow to develop (typically in older, obese individuals), and the symptoms are milder.