Role of Coenzymes

The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another.

Ex. The hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD;

The amine (-NH2) carried by pyridoxal phosphate

Ampholytes, Polyampholytes, pI and Zwitterion

Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.

For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH₂ group:

pI = [pK_a-(COOH) + pK_a-(NH3⁺₎]/2

For more complex molecules such as polyampholytes the pI is the average of the pK_a values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.

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.

Regulation of PTH secretion

Secretion of parathyroid hormone is controlled chiefly by serum [Ca²⁺] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca²⁺] is low.

Hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.

Hypermagnesemia also results in inhibition of PTH secretion.

Stimulators of PTH includes decreased serum [Ca²⁺], mild decreases in serum [Mg²⁺], and an increase in serum phosphate.

Inhibitors include increased serum [Ca²⁺], severe decreases in serum [Mg²⁺], which also produces symptoms of hypoparathyroidism (such as hypocalcemia), and calcitriol.

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 P_i → 2 lactate + 2 ATP

Anaerobic catabolism of glucose yields only 2 “high energy” bonds of ATP.

Insulin

Insulin is a polypeptide hormone synthesized in the pancreas by β-cells, which construct a single chain molecule called proinsulin. 

Insulin, secreted by the β-cells of the pancreas in response to rising blood glucose levels, is a signal that glucose is abundant.

Insulin binds to a specific receptor on the cell surface and exerts its metabolic effect by a signaling pathway that involves a receptor tyrosine kinase phosphorylation cascade.

The pancreas secretes insulin or glucagon in response to changes in blood glucose.

Each cell type of the islets produces a single hormone: α-cells produce glucagon; β-cells, insulin; and δ-cells, somatostatin.

Insulin secretion

When blood glucose rises, GLUT2 transporters carry glucose into the b-cells, where it is immediately converted to glucose 6-phosphate by hexokinase IV (glucokinase) and enters glycolysis. The increased rate of glucose catabolism raises [ATP], causing the closing of ATP-gated K+ channels in the plasma membrane. Reduced efflux of K+ depolarizes the membrane, thereby opening voltage-sensitive Ca2+ channels in the plasma membrane. The resulting influx of Ca2+ triggers the release of insulin by exocytosis.

Insulin lowers blood glucose by stimulating glucose uptake by the tissues; the reduced blood glucose is detected by the β-cell as a diminished flux through the hexokinase reaction; this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.

Insulin counters high blood glucose

Insulin stimulates glucose uptake by muscle and adipose tissue, where the glucose is converted to glucose 6-phosphate. In the liver, insulin also activates glycogen synthase and inactivates glycogen phosphorylase, so that much of the glucose 6-phosphate is channelled into glycogen.

Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease. There are two major clinical classes of diabetes mellitus: type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. In type I diabetes, the disease begins early in life and quickly becomes severe. IDDM requires insulin therapy and careful, lifelong control of the balance between dietary intake and insulin dose.

Characteristic symptoms of type I (and type II) diabetes are excessive thirst and frequent urination (polyuria), leading to the intake of large volumes of water (polydipsia)

Type II diabetes is slow to develop (typically in older, obese individuals), and the symptoms are milder.