IRON

The normal limit for iron consumption is 20 mg/day for adults, 20-30 mg/day for children and 40 mg/day for pregnant women.

Milk is considered as a poor source of iron.

Factors influencing absorption of iron Iron is absorbed by upper part of duodenum and is affected by various factors

(a) Only reduced form of iron (ferrous) is absorbed and ferric form are not absorbed

 (b) Ascorbic acid (Vitamin C) increases the absorption of iron (c) The interfering substances such as phytic acid and oxalic acid decreases absorption of iron

Regulation of absorption of Iron

Absorption of iron is regulated by three main mechanisms, which includes

(a) Mucosal Regulation

(b) Storer regulation

(c) Erythropoietic regulation

In mucosal regulation absorption of iron requires DM-1 and ferroportin. Both the proteins are down regulated by hepcidin secreted by liver. The above regulation occurs when the body irons reserves are adequate. When the body iron content gets felled, storer regulation takes place. In storer regulation the mucosal is signaled for increase in iron absorption. The erythropoietic regulation occurs in response to anemia. Here the erythroid cells will signal the mucosa to increase the iron absorption.

Iron transport in blood

The transport form of iron in blood is transferin. Transferin are glycoprotein secreted by liver. In blood, the ceruloplasmin is the ferroxidase which oxidizes ferrous to ferric state.

Storage form of iron is ferritin. Almost no iron is excreted through urine.

Anemia

Anemia is the most common nutritional deficiency disease. The microscopic appearance of anemia is characterized by microcytic hypochromic anemia

The abnormal gene responsible for hemosiderosis is located on the short arm of chromosome No.6.

The main causes of iron deficiency or anemia are

(a) Nutritional deficiency of iron (b) Lack of iron absorption (c) Hook worm infection (d) Repeated pregnancy (e) Chronic blood loss (f) Nephrosis (g) Lead poisoning

The Hemoglobin Buffer Systems

These buffer systems are involved in buffering CO₂ inside erythrocytes. The buffering capacity of hemoglobin depends on its oxygenation and deoxygenation. Inside the erythrocytes, CO₂ combines with H₂O to form carbonic acid (H₂CO₃) under the action of carbonic anhydrase.

At the blood pH 7.4, H₂CO₃ dissociates into H⁺ and HCO₃ ⁻ and needs immediate buffering.

BIOLOGICAL BUFFER SYSTEMS 

Cells and organisms maintain a specific and constant cytosolic pH, keeping biomolecules in their optimal ionic state, usually near pH 7. In multicelled organisms, the pH of the extracellular fluids (blood, for example) is also tightly regulated. Constancy of pH is achieved primarily by biological buffers : mixtures of weak acids and their conjugate bases 

Body fluids and their principal buffers

Body fluids                     Principal buffers

Extracellular fluids        {Biocarbonate buffer Protein buffer } 

Intracellular fluids         {Phosphate buffer, Protein }

Erythrocytes                 {Hemoglobin buffer}

Acids and bases can be classified as proton donors and proton acceptors, respectively. This means that the conjugate base of a given acid will carry a net charge that is more negative than the corresponding acid. In biologically relavent compounds various weak acids and bases are encountered, e.g. the acidic and basic amino acids, nucleotides, phospholipids etc.

Weak acids and bases in solution do not fully dissociate and, therefore, there is an equilibrium between the acid and its conjugate base. This equilibrium can be calculated and is termed the equilibrium constant = K_a. This is also  referred to as the dissociation constant as it pertains to the dissociation of protons from acids and bases.

In the reaction of a weak acid:

HA <-----> A^- + H⁺

the equlibrium constant can be calculated from the following equation:

K_a = [H⁺][A^-]/[HA]

As in the case of the ion product:

pK_a = -logK_a

Therefore, in obtaining the -log of both sides of the equation describing the dissociation of a weak acid we arrive at the following equation:

-logK_a = -log[H⁺][A^-]/[HA]

Since as indicated above -logK_a = pK_a and taking into account the laws of logrithms:

pK_a = -log[H⁺] -log[A^-]/[HA]

pK_a = pH -log[A^-]/[HA]

From this equation it can be seen that the smaller the pK_a value the stronger is the acid. This is due to the fact that the stronger an acid the more readily it will give up H⁺ and, therefore, the value of [HA] in the above equation will be relatively small.

Acyl-CoA Synthases (Thiokinases), associated with endoplasmic reticulum membranes and the outer mitochondrial membrane, catalyze activation of long chain fatty acids, esterifying them to coenzyme A, as shown at right. This process is ATP-dependent, and occurs in 2 steps. There are different Acyl-CoA Synthases for fatty acids of different chain lengths. 

Exergonic hydrolysis of PP_i (P~P), catalyzed by Pyrophosphatase, makes the coupled reaction spontaneous. Overall, two ~P bonds of ATP are cleaved during fatty acid activation. The acyl-coenzyme A product includes one "high energy" thioester linkage.

Summary of fatty acid activation:

• fatty acid + ATP → acyl-adenylate + PP_i
  PP_i  → P_i
• acyladenylate + HS-CoA → acyl-CoA + AMP

Overall: fatty acid + ATP + HS-CoA → acyl-CoA + AMP +  2 P_i

For most steps of the b-Oxidation Pathway, there are multiple enzymes specific for particular fatty acid chain lengths.

Fatty acid b-oxidation is considered to occur in the mitochondrial matrix. Fatty acids must enter the matrix to be oxidized. However enzymes of the pathway specific for very long chain fatty acids are associated with the inner mitochondrial membrane (facing the matrix).

Fatty acyl-CoA formed outside the mitochondria can pass through the outer mitochondrial membrane, which contains large VDAC channels, but cannot penetrate the mitochondrial inner membrane.

Transfer of the fatty acid moiety across the inner mitochondrial membrane involves carnitine.

Carnitine Palmitoyl Transferases catalyze transfer of a fatty acid between the thiol of Coenzyme A and the hydroxyl on carnitine.

Carnitine-mediated transfer of the fatty acyl moiety into the mitochondrial matrix is a 3-step process, as presented below.

1. Carnitine Palmitoyl Transferase I, an enzyme associated with the cytosolic surface of the outer mitochondrial membrane, catalyzes transfer of a fatty acid from ester linkage with the thiol of coenzyme A to the hydroxyl on carnitine.
2. Carnitine Acyltransferase, an antiporter in the inner mitochondrial membrane, mediates transmembrane exchange of fatty acyl-carnitine for carnitine.
3. Within the mitochondrial matrix (or associated with the matrix surface of the inner mitochondrial membrane, Carnitine Palmitoyl Transferase II catalyzes transfer of the fatty acid from carnitine to coenzyme A. (Carnitine exits the matrix in step 2.) The fatty acid is now esterified to coenzyme A within the mitochondrial matrix

Control of fatty acid oxidation is exerted mainly at the step of fatty acid entry into mitochondria.

Malonyl-CoA inhibits Carnitine Palmitoyl Transferase I. (Malonyl-CoA is also a precursor for fatty acid synthesis). Malonyl-CoA is produced from acetyl-CoA by the enzyme Acetyl-CoA Carboxylase

AMP-Activated Kinase, a sensor of cellular energy levels, catalyzes phosphorylation of Acetyl-CoA Carboxylase under conditions of high AMP (when ATP is low). Phosphorylation inhibits Acetyl-CoA Carboxylase, thereby decreasing malonyl-CoA production.

The decrease in malonyl-CoA concentration releases Carnitine Palmitoyl Transferase I from inhibition. The resulting increase in fatty acid oxidation generates acetyl-CoA for entry into Krebs cycle, with associated production of ATP

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.