Medical Biochemistry 2: Calcium & Phosphate Metabolism

Calcium Metabolism

• Calcium is the most abundant mineral in the human body, with an average of 1000g in an adult body.
• 99% of calcium is found in the skeleton, and 1% is found in extracellular fluid.

Functions of Calcium

• Transmission of nerve impulses
• Formation of teeth and bone
• Muscle contraction
• Blood coagulation
• Activation of enzymes
• Secretion of hormones

Food Sources and Daily Requirement

• Food sources: milk, dairy products, cereals, fish, eggs, and cabbage
• Daily requirement: 500mg/day for adults, 1200mg/day for children, 1500mg/day for pregnancy and lactation, and 1500mg/day for the elderly

Absorption of Calcium

• Absorption occurs in the first and second parts of the duodenum
• Two mechanisms of absorption: active transport process and simple diffusion

Plasma Calcium

• Normal concentration: 9-11 mg/dL
• Calcium is present in three forms: bound to proteins (about 4mg/dL), ionized form (about 5mg/dL), and complexed with bicarbonate, citrate, or phosphate (about 1mg/dL)
• Ionized form is the only physiologically active form

Factors Affecting Calcium Absorption

• Vitamin D (calcitriol) induces the formation of a carrier protein (Calbindin) for calcium transfer
• Parathyroid hormone increases calcium transport by enhancing 1α hydroxylase activity
• pH of the intestine: acidity increases calcium absorption
• Amount of carbohydrates in the diet: lactose promotes calcium absorption
• Amount of protein in the diet: amino acids (lysine and arginine) increase calcium absorption
• Phytic acid: an anti-calcifying factor that combines with calcium to form insoluble salts
• Oxalates: present in leafy vegetables, causing formation of insoluble calcium oxalates
• Phosphate: high phosphate content causes precipitation as calcium phosphate
• Malabsorption syndromes: fatty acid is not absorbed, causing formation of insoluble calcium salt

Excretion of Calcium

• Calcium leaves the body mainly in urine and feces, but also in other body tissues and fluids, such as sweat
• Renal threshold for calcium in blood: 10mg/dL

Homeostasis of Calcium

• Plasma calcium concentration is controlled by three hormones: parathyroid hormone (PTH), calcitriol, and calcitonin

Parathyroid Hormone (PTH)

• PTH secretion is stimulated in response to decreased plasma ionized calcium
• Acts on bone to cause rapid release of calcium and increased osteoclastic resorption
• Acts on kidneys to increase calcium reabsorption and decrease renal calcium excretion
• Acts on the intestine to stimulate production of calcitriol, which increases calcium absorption

Calcitriol

• Active form of vitamin D
• Increases blood calcium level by:
  • Increasing absorption of dietary calcium from the intestine
  • Increasing renal tubular reabsorption of calcium
  • Increasing osteoclast activity, causing bone demineralization

Calcitonin

• Secreted by parafollicular cells of the thyroid gland

Hypercalcemia and Hypocalcemia

• Hypercalcemia: serum calcium level > 11mg/dL
• Hypocalcemia: serum calcium level < 8.8mg/dL

Symptoms of Hypocalcemia

• Muscle cramps
• Paresthesia, especially in fingers
• Neuromuscular irritability, muscle twitching
• Tetany (intermittent muscular spasm)
• Seizures
• Bradycardia
• Rickets
• Osteoporosis

Phosphate Metabolism

• An adult body contains about 1 kg of phosphate, found in every cell of the body
• Daily requirement: 500mg/day

Food Sources

• Food sources: milk, dairy products, cereals, nuts

Forms of Phosphate in Serum

• Free ions (40%)
• Complex form with cations such as Ca2+, Mg2+, Na+, K+ (50%)
• Bound to protein (10%)

Functions of Phosphate

• Formation of bone and teeth
• Production of high energy phosphate compounds, such as ATP, CTP, GTP, and creatine phosphate
• Synthesis of nucleoside co-enzymes, such as NAD and NADP
• DNA and RNA synthesis, where phosphodiester linkages form the backbone of the structure
• Formation of phosphate esters, such as glucose-6-phosphate and phospholipids
• Activation of enzymes by phosphorylation
• Phosphate buffer system in blood, where the ratio of Na2HPO4:NaH2PO4 is 4:1.