Where is the majority of phosphorus located in the body
85% located in bones and teeth as hydroxyapatite crystals Ca10(PO4)6(OH)2
Where is the rest of phosphorus located in the body
Remaining 15% located in non-skeletal tissue (in every cell in the body) as organic phosphates/ PO4^3-
What is the skeletal function of phosphorus
Support, movement and protection
What is the non skeletal function of phosphorus
Function (Non-skeletal):
• Energy release upon oxidation of fats, carbohydrates, and proteins (e.g.
ATP); temporary storage and transfer of that energy.
•Phosphorylation:
Absorption of nutrients
Activation of many catalytic proteins
Transport of lipids (as phospholipids)
Function of certain B vitamins (e.g. Thiamin ‘B,’)
RNA and DNA = phosphorylated compounds,
phospholipids in cell walls
• Buffer: to prevent change in pH of body fluids.
How is phosphorus absorbed
Phosphorus is absorbed across epithelial brush border membranes mainly through sodium-dependent phosphate co-transporters, with NPT2 being the most important transporter in the kidney and intestine.
What are the two main methods of phosphorus absorption
Phosphorus is absorbed in the intestine via two main routes:
• Transcellular (active) route: This pathway is saturable and regulated by the active vitamin D metabolite 1,25(OH)_2D_3. It involves sodium-dependent phosphate cotransporters and becomes more relevant when dietary Pi is low. However, humans do not have adaptive mechanisms to increase absorption substantially at low intakes, unlike calcium
• Paracellular (passive) route: Most absorbed phosphorus passes via this route, which is not saturable and relies on passive diffusion between cells (paracellular transport). This pathway predominates, especially when dietary phosphorus intake is ample.
Describe NPT2 regulation
Regulation of NPT2 occurs via hormones and dietary factors:
• Parathyroid hormone (PTH), the active form of vitamin D (1,25(OH)2 D), and plasma phosphorus concentration all influence NPT2 expression and activity.
• PTH decreases NPT2 activity in the kidney by promoting endocytosis, leading to transporter degradation if PTH remains elevated.
• 1,25(OH)2 D stimulates NPT2 production by increasing its gene transcription.
• Low phosphorus levels increase NPT2 activity, likely through increased transcription and by enhancing post-translational processing of NPT2 mRNA, stabilizing the transporter for greater effectiveness.
Where is NPT2 most important
Kidney and intestine
Describe what happens to phosphorus in food before absorption
Phosphorus from food includes both inorganic (Pi) and organic forms; in the intestine, enzymes hydrolyze organic phosphorus to Pi, which is then absorbed by enterocytes.
Describe % phosphorus absorption in adults
55-70%
What factors affect phosphorus absorption
Factors Affecting Absorption
• Phosphorus absorption is reduced by aluminum-containing antacids and very large doses of calcium carbonate/CaCO3, as they bind phosphorus within the gut and hinder its uptake
• Unlike calcium, there is limited physiological adaptation to boost phosphorus absorption when intake is low
Describe phosphorus metabolism
Phosphorus metabolism in healthy adults is tightly regulated, with the kidney acting as the main control point for systemic phosphorus levels.
Overview of Phosphorus Metabolism
• In adults, urinary phosphorus excretion almost exactly matches the amount absorbed from the diet, except for minor losses through shed skin and intestinal mucosal cells.
• Thus, the kidney determines overall phosphorus balance by adjusting how much phosphorus is reabsorbed or excreted.
Details of Regulation
• Plasma inorganic phosphorus (Pi) levels are mainly determined by the amount of phosphorus ingested and absorbed from the gut.
• At low dietary phosphorus intake, plasma Pi tends to rise because the kidneys reabsorb nearly all filtered phosphorus, resulting in minimal urinary loss.
• At high dietary phosphorus intake, the kidneys increase excretion to match the absorbed level, so plasma levels remain stable and do not significantly increase
• During bone growth and development, some inorganic phosphorus is diverted from plasma into bone for mineralization.
How do we assess P status
Plasma inorganic P (H2PO4-/HPO42-) 2.5-4.4 mg/100 ml
Plasma organic P as phospholipids or bound to protein
Why is it difficult to assess P status
Difficult due to homeostatic mechanisms and plasma P in both organic and inorganic forms
What is the DRV for P
Adult RNI 550mg/day
What are UK DRVs for phosphorus based on
UK DRVs based on equimolar ratio of Ca:P
What ratio of Ca:P indicates deficiency/ hypocalcaemia
Ratio Ca:P important – ratio 0.3:1 or less lead to hypocalcaemia
What are dietary sources of phosphorus
Present in all foods but content varies, highest in milk, cheese, yogurt, carrot, peas and meat
Describe phosphorus deficiency
- hypophosphatemia (low blood P levels)
- cellular dysfunction
- whole organism level- anorexia, anaemia, muscle weakness, bone pain, rickets, osteomalacia, increased susceptibility to infection
Why is P deficiency rare
So common in food almost complete starvation required
