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

CLINICAL SIGNIFICANCE OF ENZYMES

The measurement of enzymes level in serum is applied in diagnostic application

Pancreatic Enzymes

Acute pancreatitis is an inflammatory process where auto digestion of gland was noticed with activation of the certain pancreatic enzymes. Enzymes which involves in pancreatic destruction includes α-amylase, lipase etc.,

1.  α-amylase (AMYs) are calcium dependent hydrolyase class  of metaloenzyme that catalyzes the hydrolysis of 1, 4- α-glycosidic linkages in polysaccharides. The normal values of amylase is in range of 28-100 U/L. Marked increase of 5 to 10 times the upper reference limit (URL) in AMYs activity indicates acute pancreatitis and severe glomerular impairment.

2.  Lipase is single chain glycoprotein. Bile salts and a cofactor called colipase are required for full catalytic activity of lipase. Colipase is secreted by pancreas. Increase in plasma lipase activity indicates acute pancreatitis and carcinoma of the pancreas.

Liver Enzymes

Markers of Hepatocellular Damage

1.  Aspartate transaminase (AST) Aspartate transaminase is present in high concentrations in cells of cardiac and skeletal muscle, liver, kidney and erythrocytes. Damage to any of these tissues may increase plasma AST levels.

The normal value of AST for male is <35 U/ L and for female it is <31 U/L.

2.  Alanine transaminase (ALT) Alanine transaminase is present at high concentrations in liver and to a lesser extent, in skeletal muscle, kidney and heart. Thus in case of liver damage increase in both AST and ALT were noticed. While in myocardial infarction AST is increased with little or no increase in ALT.

The normal value of ALT is <45 U/L and <34 U/L for male and female respectively

Markers of cholestasis

1.  Alkaline phosphatases

Alkaline phosphatases are a group of enzymes that hydrolyse organic phosphates at high pH. They are present in osteoblasts of bone, the cells of the hepatobiliary tract, intestinal wall, renal tubules and placenta.

Gamma-glutamyl-transferase (GGT) Gamma-glutamyl-transferase catalyzes the transfere of the γ–glutamyl group from peptides. The activity of GGT is higher in men than in women. In male the normal value of GGT activity is <55 U/L and for female it is <38 U/L.

2.  Glutamate dehydrogenase (GLD) Glutamate dehydrogenase is a mitochondrial enzyme found in liver, heart muscle and kidneys.

Muscle Enzymes

1.  Creatine Kinase Creatine kinase (CK) is most abundant in cells of brain, cardiac and skeletal.

2.  Lactate Dehydrogenase

Lactate dehydrogenase (LD) catalyses the reversible interconversion of lactate and pyruvate.

- There are two important phospholipids, Phosphatidylcholine and Phosphatidylserine found the cell membrane without which cell cannot function normally.

- Phospholipids are also important for optimal brain health as they found the cell membrane of brain cells also which help them to communicate and influence the receptors function. That is the reason food stuff which is rich in phospholipids like soy, eggs and the brain tissue of animals are good for healthy and smart brain.

- Phospholipids are the main component of cell membrane or plasma membrane. The bilayer of phospholipid molecules determine the transition of minerals, nutrients, and drugs in and out of the cell and affect various functions of them.

- As phospholipids are main component of all cell membrane, they influence a number of organs and tissues, such as the heart, blood cells and the immune system. As we grown up the amount of phospholipids decreases and reaches to decline.

- Phospholipids present in cell membrane provide cell permeability and flexibility with various substances as well its ability to move fluently. The arrangement of phospholipid molecules in lipid bilayer prevent amino acids, carbohydrates, nucleic acids, and proteins from moving across the membrane by diffusion. The lipid bi-layer is usually help to prevent adjacent molecules from sticking to each other.

- The selectivity of cell membrane form certain substances are due to the presence of hydrophobic and hydrophilic part molecules and their arrangement in bilayer. This bilayer is also maintained the normal pH of cell to keeps it functioning properly.

- Phospholipids are also useful in the treatment of memory problem associated with chronic substances as they improve the ability of organism to adapt the chronic stress.

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

Polyprotic Acids

• Some acids are polyprotic acids; they can lose more than one proton.

• In this case, the conjugate base is also a weak acid.

• For example: Carbonic acid (H2CO3 ) can lose two protons sequentially.

• Each dissociation has a unique Ka and pKa value.

Ka₁ = [H+ ][HCO₃ ^- ] / [H₂CO₃]

Ka₂ = [H+ ][CO₃ ^-2 ] / [HCO₃^- ] 

Note: (The difference between a weak acid and its conjugate base differ is one hydrogen)

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.