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.

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.

Glycogen Metabolism

The formation of glycogen from glucose is called Glycogenesis

Glycogen is a polymer of glucose residues linked mainly by a(1→ 4)  glycosidic linkages. There are a(1→6) linkages at branch points. The chains and branches are longer than shown. Glucose is stored as glycogen predominantly in liver and muscle cells

Glycogen Synthesis

Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis. As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for synthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.

UDP-glucose is formed from glucose-1-phosphate and uridine triphosphate (UTP)

glucose-1-phosphate + UTP → UDP-glucose + 2 P_i

Cleavage of PPi is the only energy cost for glycogen synthesis (1P bond per glucose residue)

Glycogenin initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes glycosylation of one of its own tyrosine residues.

Physiological regulation of glycogen metabolism

Both synthesis and breakdown of glycogen are spontaneous. If glycogen synthesis and phosphorolysis were active simultaneously in a cell, there would be a futile cycle with cleavage of 1 P bond per cycle

To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated, both by allosteric effectors and by covalent modification (phosphorylation)

Glycogen catabolism (breakdown)

Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the →(1→4) glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product.

Glycogen (n residues) + P_i → glycogen (n-1 residues) + glucose-1-phosphate

The Major product of glycogen breakdown is glucose -1-phosphate

Fate of glucose-1-phosphate in relation to other pathways:

Phosphoglucomutase catalyzes the reversible reaction:

Glucose-1-phosphate → Glucose-6-phosphate

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

Biotin

 Biotin helps release energy from carbohydrates and aids in the metabolism of fats, proteins and carbohydrates from food.

RDA The Adequate Intake (AI) for Biotin is 30 mcg/day for adult males and females

Biotin Deficiency Biotin deficiency is uncommon under normal circumstances, but symptoms include fatigue, loss of appetite, nausea, vomiting, depression, muscle pains, heart abnormalities and anemia.

Glycolysis Pathway

The reactions of Glycolysis take place in the cytosol of cells.

Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate. Initially, there is energy input corresponding to cleavage of two ~P bonds of ATP. 

1. Hexokinase catalyzes:  glucose + ATP → glucose-6-phosphate + ADP

ATP binds to the enzyme as a complex with Mg⁺⁺.

The reaction catalyzed by Hexokinase is highly spontaneous 

2. Phosphoglucose Isomerase catalyzes: 

glucose-6-phosphate (aldose) → fructose-6-phosphate (ketose)

The Phosphoglucose Isomerase mechanism involves acid/base catalysis, with ring opening, isomerization via an enediolate intermediate, and then ring closure .

3. Phosphofructokinase catalyzes: 

fructose-6-phosphate + ATP  → fructose-1,6-bisphosphate + ADP

The Phosphofructokinase reaction is the rate-limiting step of Glycolysis. The enzyme is highly regulated. 

4. Aldolase catalyzes: 

fructose-1,6-bisphosphate   → dihydroxyacetone phosphate + glyceraldehyde-3-phosphate

The Aldolase reaction is an aldol cleavage, the reverse of an aldol condensation.

5. Triose Phosphate Isomerase (TIM) catalyzes

dihydroxyacetone phosphate (ketose) → glyceraldehyde-3-phosphate (aldose)

Glycolysis continues from glyceraldehydes-3-phosphate

The equilibrium constant (K_eq) for the TIM reaction favors dihydroxyacetone phosphate, but removal of glyceraldehyde-3-phosphate by a subsequent spontaneous reaction allows throughput. 

6. Glyceraldehyde-3-phosphate Dehydrogenase catalyzes:

glyceraldehyde-3-phosphate + NAD⁺ + P_i  → 1,3,bisphosphoglycerate + NADH + H⁺

This is the only step in Glycolysis in which NAD⁺ is reduced to NADH

A cysteine thiol at the active site of Glyceraldehyde-3-phosphate Dehydrogenase has a role in catalysis . 

7. Phosphoglycerate Kinase catalyzes:

1,3-bisphosphoglycerate + ADP  →  3-phosphoglycerate + ATP

This transfer of phosphate to ADP, from the carboxyl group on 1,3-bisphosphoglycerate, is reversible

8. Phosphoglycerate Mutase catalyzes:  3-phosphoglycerate → 2-phosphoglycerate

Phosphate is shifted from the hydroxyl on C3 of 3-phosphoglycerate to the hydroxyl on C2.  

9. Enolase catalyzes:  2-phosphoglycerate  → phosphoenolpyruvate + H₂O

This Mg⁺⁺-dependent dehydration reaction is inhibited by fluoride. Fluorophosphate forms a complex with Mg⁺⁺ at the active site .

10. Pyruvate Kinase catalyzes:  phosphoenolpyruvate + ADP  → pyruvate + ATP

This transfer of phosphate from PEP to ADP is spontaneous. 

Balance sheet for high energy bonds of ATP: 

• 2 ATP expended
• 4 ATP produced (2 from each of two 3C fragments from glucose) 
• Net Production of 2~ P bonds of ATP per glucose