NEET MDS Lessons
Biochemistry
Growth hormone
Growth hormone (GH or HGH), also known as somatotropin or somatropin, is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans.
Growth hormone is a single-chain polypeptide that is synthesized, stored, and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.
Regulation of growth hormone secretion
Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH or somatocrinin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary.
GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.
Regulation
Stimulators of growth hormone (GH) secretion include peptide hormones, ghrelin, sex hormones, hypoglycemia, deep sleep, niacin, fasting, and vigorous exercise.
Inhibitors of GH secretion include somatostatin, circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus), hyperglycemia, glucocorticoids, and dihydrotestosterone.
Clinical significance
The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH excess. The adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.
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
Keq, Kw and pH
As H2O is the medium of biological systems one must consider the role of this molecule in the dissociation of ions from biological molecules. Water is essentially a neutral molecule but will ionize to a small degree. This can be described by a simple equilibrium equation:
H2O <-------> H+ + OH-
This equilibrium can be calculated as for any reaction:
Keq = [H+][OH-]/[H2O]
Since the concentration of H2O is very high (55.5M) relative to that of the [H+] and [OH-], consideration of it is generally removed from the equation by multiplying both sides by 55.5 yielding a new term, Kw:
Kw = [H+][OH-]
This term is referred to as the ion product. In pure water, to which no acids or bases have been added:
Kw = 1 x 10-14 M2
As Kw is constant, if one considers the case of pure water to which no acids or bases have been added:
[H+] = [OH-] = 1 x 10-7 M
This term can be reduced to reflect the hydrogen ion concentration of any solution. This is termed the pH, where:
pH = -log[H+]
The pH scale
An acidic solution is one in which [H+ ] > [OH- ]
•In an acidic solution, [H+ ] > 10-7 , pH < 7.
•A basic solution is when [OH- ] > [H+ ].
•In a basic solution, [OH- ] > 10-7 , pOH < 7, and pH >7.
• When the pH = 7, the solution is neutral.
•Physiological pH range is 6.5 to 8.0
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.
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
MAGNESIUM
The normal serum level of Magnesium is 1.8 to 2.2. mg/dl.
Functions of Magnesium
(a) Irritability of neuromuscular tissues is lowered by Magnesium
(b) Magnesium deficiency leads to decrease in Insulin dependent uptake of glucose
(c) Magnesium supplementation improves glucose tolerance
Causes such as liver cirrhosis, protein calorie malnutrition and hypo para thyroidism leads to hypomagnesemia
The main causes of hypermagnesemia includes renal failure, hyper para thyroidism, rickets, oxalate poisoning and multiple myeloma.