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

Glycogen Storage Diseases are genetic enzyme deficiencies associated with excessive glycogen accumulation within cells.

• When an enzyme defect affects mainly glycogen storage in liver, a common symptom is hypoglycemia (low blood glucose), relating to impaired mobilization of glucose for release to the blood during fasting.
• When the defect is in muscle tissue, weakness and difficulty with exercise result from inability to increase glucose entry into Glycolysis during exercise.

Various type of Glycogen storage disease are

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

FAT-SOLUBLE VITAMINS

The fat-soluble vitamins, A, D, E, and K, are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess than water-soluble vitamins.

VITAMIN A: RETINOL

 Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division, gene expression, and regulation of the immune system.

The skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers.

One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene. The Recommended Dietary Allowance (RDA) for vitamin A is 900 mcg/ day for adult males and 700 mcg/ day for adult females.

Vitamin A Deficiency

Vitamin A deficiency is rare, but the disease that results is known as xerophthalmia.

Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth.

Vitamin A toxicity The Tolerable Upper Intake Level (UL) for adults is 3,000 mcg RAE.

VITAMIN D

Vitamin D plays a critical role in the body’s use of calcium and phosphorous. It works by increasing the amount of calcium absorbed from the small intestine, helping to form and maintain bones.

Vitamin D benefits the body by playing a role in immunity and controlling cell growth. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth.

RDA  From 12 months to age fifty, the RDA is set at 15 mcg.

20 mcg of cholecalciferol equals 800 International Units (IU), which is the recommendation for maintenance of healthy bone for adults over fifty.

Vitamin D Deficiency

Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults may result in osteomalacia (muscle and bone weakness), and osteoporosis (loss of bone mass).

Vitamin D toxicity

The Tolerable Upper Intake Level (UL) for vitamin D is set at 100 mcg for people 9 years of age and older. High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning.

VITAMIN E: TOCOPHEROL

Vitamin E benefits the body by acting as an antioxidant, and protecting vitamins A and C, red blood cells, and essential fatty acids from destruction.

RDA  One milligram of alpha-tocopherol equals to 1.5 International Units (IU). RDA guidelines state that males and females over the age of 14 should receive 15 mcg of alpha-tocopherol per day.

Vitamin E Deficiency Vitamin E deficiency is rare. Cases of vitamin E deficiency usually only occur in premature infants and in those unable to absorb fats.

VITAMIN K

Vitamin K is naturally produced by the bacteria in the intestines, and plays an essential role in normal blood clotting, promoting bone health, and helping to produce proteins for blood, bones, and kidneys.

RDA

Males and females age 14 - 18: 75 mcg/day; Males and females age 19 and older: 90 mcg/day

Vitamin K Deficiency

Hemorrhage can occur due to sufficient amounts of vitamin K.

Vitamin K deficiency may appear in infants or in people who take anticoagulants, such as Coumadin (warfarin), or antibiotic drugs.

Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week.

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

Vitamin B12: Cobalamin

Vitamin B12, also known as cobalamin, aids in the building of genetic material, production of normal red blood cells, and maintenance of the nervous system.

RDA The Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4 mcg/day for adult males and females

Vitamin B12 Deficiency

Vitamin B12 deficiency most commonly affects strict vegetarians (those who eat no animal products), infants of vegan mothers, and the elderly. Symptoms of deficiency include anemia, fatigue, neurological disorders, and degeneration of nerves resulting in numbness and tingling.