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

Factors regulating blood calcium level

(i) Vitamin D

(a) Vitamin D and absorption of calcium: Active form of calcium is calcitriol. Calcitriol enters intestinal wall and binds to cytoplasmic receptor and then binds with DNA causes depression and consequent transcription of gene code for calbindin. Due to increased availability of calbindin, absorption of calcium increases leading to increased blood calcium level.
(b) Vitamin D and Bone: Vitamin D activates osteoblast, bone forming cells & also stimulates secretion of alkaline phosphatase. Due to this enzyme, calcium and phosphorus increase.

(c) Vitamin D and Kidney: Calcitriol increase reabsorption of calcium and phosphorus by renal tubules.

(ii) Parathyroid  hormone (PTH)

Normal PTH level in serum is 10-60ng/l.

(a) PTH and bones: In bone, PTH causes demineralization. It also causes recreation of collagenase from osteoclast  leads to loss of matrix and bone resorption. As a result, mucopolysacharides and hydroxyproline are excreted in urine.

(b) PTH and Kidney: In kidney, PTH causes increased reabsorption of calcium but decreases reabsorption of phosphorus from kidney tubules.

(iii) Calcitonin Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases osteoblasts.

Hyper Calcemia When plasma Ca2+ level is more than 11mg/dl is called Hypercalcemia. It is due to parathyroid adenoma or ectopic PTH secreting tumor. calcium excreted in urine decreases excretion of chloride causing hyperchloremic acidosis.

Hypocalcemia Plasma calcium level less than 8mg/dl is called hypocalcemia. Tetany due to accidental surgical removal of parathyroid glands or by autoimmune disease. In tetany, neuromuscular irritability is increased. Increased Q-7 internal in ECG is seen. Main manifestation is carpopedal spasm. Laryngismus and stridor are also observed.

HORMONES

A hormone is a chemical that acts as a messenger transmitting a signal from one cell to another. When it binds to another cell which is the target of the message, the hormone can alter several aspects of cell function, including cell growth, metabolism, or other function.

Hormones can be classified on three primary ways as following:

1.  Autocrine: An autocrine hormone is one that acts on the same cell that released it.

2.  Paracrine: A paracrine hormone is one that acts on cells which are nearby relative to the cell which released it. An example of paracrine hormones includes growth factors, which are proteins that stimulate cellular proliferation and differentiation.

3. Endocrine: An endocrine hormone is one that is released into the bloodstream by endocrine glands. The receptor cells are distant from the source. An example of an endocrine hormone is insulin, which is released by the pancreas into the bloodstream where it regulates glucose uptake by liver and muscle cells.

VITAMINS

Based on solubility Vitamins are classified as either fat-soluble (lipid soluble) or water-soluble. Vitamins A, D, E and K are fat-soluble

Vitamin C and B is water soluble.

B-COMPLEX VITAMINS

Eight of the water-soluble vitamins are known as the vitamin B-complex group: thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine), folate (folic acid), vitamin B12, biotin and pantothenic acid.

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.

Weak Acids and pKa

• The strength of an acid can be determined by its dissociation constant, Ka.

• Acids that do not dissociate significantly in water are weak acids.

• The dissociation of an acid is expressed by the following reaction: HA = H⁺ + A^- and the dissociation constant Ka = [H⁺ ][A^- ] / [HA]  

• When Ka < 1, [HA] > [H⁺ ][A^- ] and HA is not significantly dissociated. Thus, HA is a weak acid when ka < 1.

• The lesser the value of Ka, the weaker the acid.

• Similar to pH, the value of Ka can also be represented as pKa.

• pKa = -log Ka.

• The larger the pKa, the weaker the acid.

• pKa is a constant for each conjugate acid and its conjugate base pair.

• Most biological compounds are weak acids or weak bases.