K_eq, K_w and pH

As H₂O is the medium of biological systems one must consider the role of this molecule in the dissociation of ions from biological molecules. Water is essentially a neutral molecule but will ionize to a small degree. This can be described by a simple equilibrium equation:

H₂O <-------> H⁺ + OH^-

This equilibrium can be calculated as for any reaction:

K_eq = [H⁺][OH^-]/[H₂O]

Since the concentration of H₂O is very high (55.5M) relative to that of the [H⁺] and [OH^-], consideration of it is generally removed from the equation by multiplying both sides by 55.5 yielding a new term, K_w:

K_w = [H⁺][OH^-]

This term is referred to as the ion product. In pure water, to which no acids or bases have been added:

K_w = 1 x 10^-14 M²

As K_w is constant, if one considers the case of pure water to which no acids or bases have been added:

[H⁺] = [OH^-] = 1 x 10^-7 M

This term can be reduced to reflect the hydrogen ion concentration of any solution. This is termed the pH, where:

pH = -log[H⁺]

Glycolysis enzymes are located in the cytosol of cells.  Pyruvate enters the mitochondrion to be metabolized further

Mitochondrial compartments: The mitochondrial matrix contains Pyruvate Dehydrogenase and enzymes of Krebs Cycle, plus other pathways such as fatty acid oxidation. 

Pyruvate Dehydrogenase catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA

FAD (Flavin Adenine Dinucleotide) is a derivative of the B-vitamin riboflavin (dimethylisoalloxazine-ribitol). The flavin ring system undergoes oxidation/reduction as shown below. Whereas NAD⁺ is a coenzyme that reversibly binds to enzymes, FAD is a prosthetic group, that is permanently part of the complex. 

FAD accepts and donates 2 electrons with 2 protons (2 H):

Thiamine pyrophosphate (TPP) is a derivative of  thiamine (vitamin B₁). Nutritional deficiency of thiamine leads to the disease beriberi. Beriberi affects especially the brain, because TPP is required for carbohydrate metabolism, and the brain depends on glucose metabolism for energy

Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism. The "high energy" thioester linkage makes it an excellent donor of the acetate moiety

For example, acetyl CoA functions as:

• input to the Krebs Cycle, where the acetate moiety is further degraded to CO₂.
• donor of acetate for synthesis of fatty acids, ketone bodies, and cholesterol.

ATPs  formed in TCA cycle from one molecule of Pyruvate

1. 3ATP            7. 3ATP          5. 3 ATP                     

 8. 1 ATP         9. 2 ATP          11.3 ATP         Total =15 ATP.

 ATPS formed from one molecule of Acetyl CoA =12ATP

ATPs formed from one molecule of glucose after complete oxidation

One molecule of glucose -->2 molecules of pyruvate

['By glycolysis] ->8 ATP

2 molecules of pyruvate [By TCA cycle] -> 30 ATP

Total = 38 ATP

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.

STEROIDS
Steroids  are the compounds containing a cyclic steroid nucleus  (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene  nucleus (rings A, B and C) to which a cyclopentane ring (D)  is attached.

Steroids  are the compounds containing a cyclic steroid nucleus  (or ring) namely cyclopentanoperhydrophenanthrene (CPPP).It consists of a phenanthrene  nucleus (rings A, B and C) to which a cyclopentane ring (D)  is attached.

There are several steroids in the biological system. These include cholesterol, bile acids, vitamin D, sex hormones, adrenocortical hormones,sitosterols, cardiac glycosides and alkaloids

During fasting or carbohydrate starvation, oxaloacetate is depleted in liver because it is used for gluconeogenesis. This impedes entry of acetyl-CoA into Krebs cycle. Acetyl-CoA then is converted in liver mitochondria to ketone bodies, acetoacetate and b-hydroxybutyrate.

 Three enzymes are involved in synthesis of ketone bodies:

b-Ketothiolase. The final step of the b-oxidation pathway runs backwards, condensing 2 acetyl-CoA to produce acetoacetyl-CoA, with release of one CoA.

HMG-CoA Synthase catalyzes condensation of a third acetate moiety (from acetyl-CoA) with acetoacetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA).

HMG-CoA Lyase cleaves HMG-CoA to yield acetoacetate plus acetyl-CoA.

 b-Hydroxybutyrate Dehydrogenase catalyzes inter-conversion of the ketone bodies acetoacetate and b-hydroxybutyrate.

Ketone bodies are transported in the blood to other tissue cells, where they are converted back to acetyl-CoA for catabolism in Krebs cycle

ZINC

The enzyme RNA polymerase, which is required for transcription, contains zinc and it is essential for protein bio synthesis.

Deficiency in Zinc leads to poor wound healing, lesions of skin impaired spermatogenesis, hyperkeratosis, dermatitis and alopecia