143involved in phosphate homeostasis. It acts in association with its co- receptor
klotho and inhibits the translocation of intracellular sodium phosphorus co-
transporter (NaPi 2a and 2c) to the cell membrane in proximal convoluted
tubule, resulting in phosphaturia. In addition, it also inhibits renal 1
α-hydroxylase activity, thereby decreasing intestinal phosphate reabsorption.
Further, FGF-23 possibly suppresses PTH secretion. Recently, it has been
shown that FGF-23 has a role in calcium homeostasis by promoting calcium
reabsorption in the distal tubule through upregulation of transient receptor
potential vanilloid‐5 (TRPV-5).- What is klotho?
“Klotho” is named after a Greek Goddess, who spins the thread of human life.
Klotho is a gene that encodes a protein which is present in three forms; trans-
membrane, secreted, and soluble form. The transmembrane klotho is a mem-
brane-bound form, while soluble and secreted klotho are present in circulation.
Soluble klotho is a truncated form of the extracellular domain of transmem-
brane klotho, whereas secreted klotho represents the entire molecule. The
transmembrane form is expressed in multiple tissues, especially in the kidney
and acts as a co-receptor for FGF-23 and results in phosphaturia and suppres-
sion of renal 1α-hydroxylase and PTH. In addition, it has antiaging and
anti- IGF1 effects. Secreted as well as soluble klotho may act alone or in concert
with FGF-23 and has antioxidant, antiapoptotic, and anti-wnt signaling
effects. FGF-23-klotho complex is possibly regulated by phosphate, PTH, and
1,25 (OH) 2 D.- How is vitamin D formed in the body?
Endogenous vitamin D synthesis occurs in the Malpighian layer of epidermis
on exposure to ultraviolet B rays (wave length 290–315 nm). The cutaneous
synthesis contributes to 80 % of circulating vitamin D and the rest is provided
by diet. On exposure to sunlight, 7-dehydrocholesterol is converted to pre-vita-
min D 3 which rapidly photoisomerizes to vitamin D 3 (cholecalciferol). This
form of vitamin D is biologically inactive and requires hepatic and renal
hydroxylations to form 25-hydroxy vitamin D 3 [25(OH)D] and 1,25-dihydroxy
vitamin D 3 [1,25(OH) 2 D], respectively. The enzyme 1α-hydroxylase involved
in renal hydroxylation is tightly regulated. 1,25(OH) 2 D is considered as the
active form of vitamin D as the affinity of 1,25(OH) 2 D to vitamin D receptor
(VDR) is 500- to 1000-fold higher as compared to 25(OH)D. However, the
serum concentration of 25(OH)D is about 500 times higher than that of
1,25(OH) 2 D, hence biological activity of 25(OH)D cannot be excluded. The
synthesis of vitamin D is summarized in the figure given below (Fig. 5.7).5 Rickets–Osteomalacia