NEET MDS Lessons
Biochemistry
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
The pentose phosphate pathway is primarily an anabolic pathway that utilizes the 6 carbons of glucose to generate 5 carbon sugars and reducing equivalents. However, this pathway does oxidize glucose and under certain conditions can completely oxidize glucose to CO2 and water. The primary functions of this pathway are:
- To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.
- To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
- Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates
Enzymes that function primarily in the reductive direction utilize the NADP+/NADPH cofactor pair as co-factors as opposed to oxidative enzymes that utilize the NAD+/NADH cofactor pair. The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis and lactating mammary gland have high levels of the PPP enzymes. In fact 30% of the oxidation of glucose in the liver occurs via the PPP. Additionally, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione. The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source, therefore, any rapidly proliferating cell needs large quantities of NADPH.
Regulation: Glucose-6-phosphate Dehydrogenase is the committed step of the Pentose Phosphate Pathway. This enzyme is regulated by availability of the substrate NADP+. As NADPH is utilized in reductive synthetic pathways, the increasing concentration of NADP+ stimulates the Pentose Phosphate Pathway, to replenish NADPH
Anaerobic organisms lack a respiratory chain. They must reoxidize NADH produced in Glycolysis through some other reaction, because NAD+ is needed for the Glyceraldehyde-3-phosphate Dehydrogenase reaction (see above). Usually NADH is reoxidized as pyruvate is converted to a more reduced compound, that may be excreted.
The complete pathway, including Glycolysis and the re-oxidation of NADH, is called fermentation.
For example, Lactate Dehydrogenase catalyzes reduction of the keto group in pyruvate to a hydroxyl, yielding lactate, as NADH is oxidized to NAD+.
Skeletal muscles ferment glucose to lactate during exercise, when aerobic metabolism cannot keep up with energy needs. Lactate released to the blood may be taken up by other tissues, or by muscle after exercise, and converted via the reversible Lactate Dehydrogenase back to pyruvate
Fermentation Pathway, from glucose to lactate (omitting H+):
glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP
Anaerobic catabolism of glucose yields only 2 “high energy” bonds of ATP.
Niacin: Vitamin B3, Nicotinamide, Nicotinic Acid Niacin, or vitamin B3,
is involved in energy production, normal enzyme function, digestion, promoting normal appetite, healthy skin, and nerves.
RDA Males: 16 mg/day; Females: 14 mg/day
Niacin Deficiency : Pellagra is the disease state that occurs as a result of severe niacin deficiency. Symptoms include cramps, nausea, mental confusion, and skin problems.
Erythrocytes and the Pentose Phosphate Pathway
The predominant pathways of carbohydrate metabolism in the red blood cell (RBC) are glycolysis, the PPP and 2,3-bisphosphoglycerate (2,3-BPG) metabolism (refer to discussion of hemoglobin for review of the synthesis and role role of 2,3-BPG).
Glycolysis provides ATP for membrane ion pumps and NADH for re-oxidation of methemoglobin. The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione.
The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H2O2, that in turn results in a weakening of the cell wall and concomitant hemolysis.
Accumulation of H2O2 also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall.
Glutathione removes peroxides via the action of glutathione peroxidase.
The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH.
Any defect in the production of NADPH could, therefore, have profound effects on erythrocyte survival.
The amino acids buffer system
Amino acids contain in their molecule both an acidic (− COOH) and a basic (− NH2) group. They can be visualized as existing in the form of a neutral zwitterion in which a hydrogen atom can pass between the carboxyl and amino groups.
By the addition or subtraction of a hydrogen ion to or from the zwitterion, either the cation or anion form will be produced
Thus, when OH− ions are added to the solution of amino acid, they take up H+ from it to form water, and the anion is produced. If H+ ions are added, they are taken up by the zwitterion to produce the cation form. In practice, if NaOH is added, the salt H2N - CH2 - COONa would be formed. and the addition of HCl would result in the formation of amino acid hydrochloride.
LIPIDS
The lipids are a heterogeneous group of compounds, including fats, oils, steroids, waxes, and related compounds, which are related more by their physical than by their chemical properties.
Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents.
Most membrane lipids are amphipathic, having a non-polar end and a polar end
Lipids are important in biological systems because they form the cell membrane, a mechanical barrier that divides a cell from the external environment.
Lipids also provide energy for life and several essential vitamins are lipids.
Lipids can be divided in two major classes, nonsaponifiable lipids and saponifiable lipids.
A nonsaponifiable lipid cannot be broken up into smaller molecules by hydrolysis, which includes triglycerides, waxes, phospholipids, and sphingolipids.
A saponifiable lipid contains one or more ester groups allowing it to undergo hydrolysis in the presence of an acid, base, or enzyme.
Nonsaponifiable lipids include steroids, prostaglandins, and terpenes
Nonpolar lipids, such as triglycerides, are used for energy storage and fuel.
Polar lipids, which can form a barrier with an external water environment, are used in membranes.
Polar lipids include glycerophospholipids and sphingolipids.
Fatty acids are important components of all of these lipids.
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.