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Biochemistry

The input to fatty acid synthesis is acetyl-CoA, which is carboxylated to malonyl-CoA.

The ATP-dependent carboxylation provides energy input. The CO2 is lost later during condensation with the growing fatty acid. The spontaneous decarboxylation drives the condensation. 

 fatty acid synthesis
acetyl-CoA + 7 malonyl-CoA + 14 NADPH palmitate + 7 CO2 + 14 NADP+ + 8 CoA

ATP-dependent synthesis of malonate:
8 acetyl-CoA + 14 NADPH + 7 ATP palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi

Fatty acid synthesis occurs in the cytosol. Acetyl-CoA generated in the mitochondria is transported to the cytosol via a shuttle mechanism involving citrate

Weak Acids and pKa

• The strength of an acid can be determined by its dissociation constant, Ka.

• Acids that do not dissociate significantly in water are weak acids.

• The dissociation of an acid is expressed by the following reaction: HA = H+ + A- and the dissociation constant Ka = [H+ ][A- ] / [HA]  

• When Ka < 1, [HA] > [H+ ][A- ] and HA is not significantly dissociated. Thus, HA is a weak acid when ka < 1.

• The lesser the value of Ka, the weaker the acid.

• Similar to pH, the value of Ka can also be represented as pKa.

• pKa = -log Ka.

• The larger the pKa, the weaker the acid.

• pKa is a constant for each conjugate acid and its conjugate base pair.

• Most biological compounds are weak acids or weak bases.

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.

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.

FACTORS AFFECTING ENZYME ACTIVITY

Velocity or rate of enzymatic reaction is assessed by the rate of change in concentration of substrate or product at a given time duration. Various factors which affect the activity of enzymes include:

1. Substrate concentration

2. Enzyme concentration

3. Product concentration

4. Temperature 5. Hydrogen ion concentration (pH)

6. Presence of activators

7. Presence of inhibitor

 

Effect of substrate Concentration :  Reaction velocity of an enzymatic process increases with constant enzyme concentration and increase in substrate concentration.

Effect of enzyme Concentration: As there is optimal substrate concentration, rate of an enzymatic reaction or velocity (V) is directly proportional to the enzyme concentration.

Effect of product concentration In case of a reversible reaction catalyzed by a enzyme, as per the law of mass action the rate of reaction is slowed down with equilibrium. So, rate of reaction is slowed, stopped or even reversed with increase in product concentration

Effect of temperature: Velocity of enzymatic reaction increases with temperature of the medium which they are most efficient and the same is termed as optimum temperature.

Effect of pH: Many enzymes are most efficient in the region of pH 6-7, which is the pH of the cell. Outside this range, enzyme activity drops off very rapidly. Reduction in efficiency caused by changes in the pH is due to changes in the degree of ionization of the substrate and enzyme.

Highly acidic or alkaline conditions bring about a denaturation and subsequent loss of enzymatic activity

Exceptions such as pepsin (with optimum pH 1-2), alkaline phosphatase (with optimum pH 9-10) and acid phosphatase (with optimum pH 4-5)

Presence of activators Presence of certain inorganic ions increases the activity of enzymes. The best examples are chloride ions activated salivary amylase and calcium activated lipases.

Effect of Inhibitors The catalytic enzymatic reaction may be inhibited by substances which prevent the formation of a normal enzyme-substrate complex. The level of inhibition then depends entirely upon the relative concentrations of the true substrate and the inhibitor

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.

VITAMINS

Based on solubility Vitamins are classified as either fat-soluble (lipid soluble) or water-soluble. Vitamins A, D, E and K are fat-soluble

Vitamin C and B is water soluble.

B-COMPLEX VITAMINS

Eight of the water-soluble vitamins are known as the vitamin B-complex group: thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine), folate (folic acid), vitamin B12, biotin and pantothenic acid.

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