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.

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

FATTY  ACIDS

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end.

• are usually in esterified form as major components of other lipids

• are often complexed in triacylglycerols (TAGs)

• most have an even number of carbon atoms (usually 14 to 24)

• are synthesized by concatenation of C2 units.

• C16 & C18 FAs are the most common FAs in higher plants and animals

• Are either:

—saturated (all C-C bonds are single bonds) or

—unsaturated (with one or more double bonds in the chain)

—monounsaturated (a single double bond)

1.Example of monounsaturated FA: Oleic acid 18:1(9) (the number in unsaturated FA parentheses indicates that the double bond is between carbons 9 & 10)

2. Double bonds are almost all in the cis conformation

—polyunsaturated (more then one double bond)

Polyunsaturated fatty acids contain 2 or more double bonds. They usually occur at every third carbon atom towards the methyl terminus (-CH3 ) of the molecule. Example of polyunsaturated FA: Linoleic acid 18:2(9,12)

• the number of double bonds in FAs varies from 1 to 4 (usually), but in most bacteria it is rarely more than 1

Saturated FAs are highly flexible molecules that can assume a wide range of conformations because there is relatively free rotation about their C-C bonds.

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.

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

Riboflavin: Vitamin B2

Riboflavin, or vitamin B2, helps to release energy from foods, promotes good vision, and healthy skin. It also helps to convert the amino acid tryptophan (which makes up protein) into niacin.

RDA Males: 1.3 mg/day; Females: 1.1 mg/day

Deficiency : Symptoms of deficiency include cracks at the corners of the mouth, dermatitis on nose and lips, light sensitivity, cataracts, and a sore, red tongue.