NEET MDS Lessons
Biochemistry
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.
Gluconeogenesis
It is the process by which Glucose or glycogen is formed from non carbohydrate substances.
Gluconeogenesis occurs mainly in liver.
Gluconeogenesis inputs:
The source of pyruvate and oxaloacetate for gluconeogenesis during fasting or carbohydrate starvation is mainly amino acid catabolism. Some amino acids are catabolized to pyruvate, oxaloacetate, Muscle proteins may break down to supply amino acids. These are transported to liver where they are deaminated and converted to gluconeogenesis inputs.
Glycerol, derived from hydrolysis of triacylglycerols in fat cells, is also a significant input to gluconeogenesis
Glycolysis & Gluconeogenesis pathways are both spontaneous If both pathways were simultaneously active within a cell it would constitute a "futile cycle" that would waste energy
Glycolysis yields 2~P bonds of ATP.
Gluconeogenesis expends 6~P bonds of ATP and GTP.
A futile cycle consisting of both pathways would waste 4 P.bonds per cycle.To prevent this waste, Glycolysis and Gluconeogenesis pathways are reciprocally regulated.
Thyroid Hormones
Thyroid hormones (T4 and T3) are tyrosine-based hormones produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland, are primarily responsible for regulation of metabolism. Iodine is necessary for the production of T3 (triiodothyronine) and T4 (thyroxine).
A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as goitre.
Thyroid hormones are transported by Thyroid-Binding Globulin
Thyroxine binding globulin (TBG), a glycoprotein binds T4 and T3 and has the capacity to bind 20 μg/dL of plasma.
Diseases
1. Hyperthyroidism (an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.
2 Hypothyroidism (an example is Hashimoto’s thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
These can be synthesized by the body from other compounds.
| Non-Essential Amino Acids | Key Functions |
|---|---|
| Alanine | Energy production, glucose metabolism |
| Asparagine | Nervous system development |
| Aspartic acid | DNA synthesis, neurotransmission |
| Glutamic acid | Brain function, neurotransmitter |
| Serine | Cell membranes, metabolism |
The body makes these from carbohydrates and other amino acids.
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
| Enzyme | Clinical Use | Indicates |
|---|---|---|
| ALT (SGPT) | Specific to liver injury | Hepatitis, liver necrosis |
| AST (SGOT) | Found in liver, heart, muscle | Liver disease, myocardial infarction |
| ALP | Bile duct obstruction, bone disease | Cholestasis, bone metastases |
| GGT | Alcoholic liver disease, biliary obstruction | Alcohol abuse, hepatobiliary disease |
| LDH | Non-specific, elevated in many conditions | Liver, cardiac, or hemolytic disorders |
FLUORIDE
The safe limit of fluorine is about 1PPM in water. But excess of fluoride causes Flourosis
Flourosis is more dangerous than caries. When Fluoride content is more than 2 PPM, it will cause chronic intestinal upset, gastroenteritis, loss of weight, osteosclerosis, stratification and discoloration of teeth