Hypophosphatasia: Nature’s window on alkaline phosphatase function in humans

Michael P. Whyte

doi:10.1016/B978-0-12-814841-9.00066-X

Hypophosphatasia: Nature’s window on alkaline phosphatase function in humans

Michael P. Whyte

Institute of Clinical and Translational Sciences (ICTS)

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

3 Scopus citations

Abstract

Alkaline phosphatase (ALP) was discovered by Robert Robison, PhD, in 1923. During the next decade, he and his coworkers would advance his hypothesis that this phosphomonoester phosphohydrolase functioned importantly in skeletal calcification, emphasizing the liberation of inorganic phosphate (Pi), perhaps from a hexosephosphoric ester substrate. Liberation of Pi to bind with calcium (Ca⁺⁺) would allow for hydroxyapatite crystal formation and growth. However, by 1932 Robison had concluded that some additional unknown factor conditioned this process. As I will review, this proved to be the ALP natural substrate and inhibitor of biomineralization, inorganic pyrophosphate.

Original language	English
Title of host publication	Principles of Bone Biology
Publisher	Elsevier
Pages	1569-1599
Number of pages	31
ISBN (Electronic)	9780128148419
DOIs	https://doi.org/10.1016/B978-0-12-814841-9.00066-X
State	Published - Jan 1 2019

Keywords

Alkaline phosphatase
Asfotase alfa
Calcification
Enzyme replacement
Epilepsy
Hydroxyapatite
Hypophosphatasia
Inborn error of metabolism
Inorganic phosphate
Inorganic pyrophosphate
Mineralization
Osteomalacia
Phosphomonoester phosphohydrolase
Pyridoxal phosphate
Pyrophosphatase
Rickets
Tissue-nonspecific alkaline phosphatase Vitamin B

Access to Document

10.1016/B978-0-12-814841-9.00066-X

Cite this

@inbook{cf097b537409426db9309d5d24aa0043,

title = "Hypophosphatasia: Nature{\textquoteright}s window on alkaline phosphatase function in humans",

abstract = "Alkaline phosphatase (ALP) was discovered by Robert Robison, PhD, in 1923. During the next decade, he and his coworkers would advance his hypothesis that this phosphomonoester phosphohydrolase functioned importantly in skeletal calcification, emphasizing the liberation of inorganic phosphate (Pi), perhaps from a hexosephosphoric ester substrate. Liberation of Pi to bind with calcium (Ca++) would allow for hydroxyapatite crystal formation and growth. However, by 1932 Robison had concluded that some additional unknown factor conditioned this process. As I will review, this proved to be the ALP natural substrate and inhibitor of biomineralization, inorganic pyrophosphate.",

keywords = "Alkaline phosphatase, Asfotase alfa, Calcification, Enzyme replacement, Epilepsy, Hydroxyapatite, Hypophosphatasia, Inborn error of metabolism, Inorganic phosphate, Inorganic pyrophosphate, Mineralization, Osteomalacia, Phosphomonoester phosphohydrolase, Pyridoxal phosphate, Pyrophosphatase, Rickets, Tissue-nonspecific alkaline phosphatase Vitamin B",

author = "Whyte, {Michael P.}",

year = "2019",

month = jan,

day = "1",

doi = "10.1016/B978-0-12-814841-9.00066-X",

language = "English",

pages = "1569--1599",

booktitle = "Principles of Bone Biology",

publisher = "Elsevier",

}

TY - CHAP

T1 - Hypophosphatasia

T2 - Nature’s window on alkaline phosphatase function in humans

AU - Whyte, Michael P.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Alkaline phosphatase (ALP) was discovered by Robert Robison, PhD, in 1923. During the next decade, he and his coworkers would advance his hypothesis that this phosphomonoester phosphohydrolase functioned importantly in skeletal calcification, emphasizing the liberation of inorganic phosphate (Pi), perhaps from a hexosephosphoric ester substrate. Liberation of Pi to bind with calcium (Ca++) would allow for hydroxyapatite crystal formation and growth. However, by 1932 Robison had concluded that some additional unknown factor conditioned this process. As I will review, this proved to be the ALP natural substrate and inhibitor of biomineralization, inorganic pyrophosphate.

AB - Alkaline phosphatase (ALP) was discovered by Robert Robison, PhD, in 1923. During the next decade, he and his coworkers would advance his hypothesis that this phosphomonoester phosphohydrolase functioned importantly in skeletal calcification, emphasizing the liberation of inorganic phosphate (Pi), perhaps from a hexosephosphoric ester substrate. Liberation of Pi to bind with calcium (Ca++) would allow for hydroxyapatite crystal formation and growth. However, by 1932 Robison had concluded that some additional unknown factor conditioned this process. As I will review, this proved to be the ALP natural substrate and inhibitor of biomineralization, inorganic pyrophosphate.

KW - Alkaline phosphatase

KW - Asfotase alfa

KW - Calcification

KW - Enzyme replacement

KW - Epilepsy

KW - Hydroxyapatite

KW - Hypophosphatasia

KW - Inborn error of metabolism

KW - Inorganic phosphate

KW - Inorganic pyrophosphate

KW - Mineralization

KW - Osteomalacia

KW - Phosphomonoester phosphohydrolase

KW - Pyridoxal phosphate

KW - Pyrophosphatase

KW - Rickets

KW - Tissue-nonspecific alkaline phosphatase Vitamin B

UR - http://www.scopus.com/inward/record.url?scp=85083198331&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-814841-9.00066-X

DO - 10.1016/B978-0-12-814841-9.00066-X

M3 - Chapter

AN - SCOPUS:85083198331

SP - 1569

EP - 1599

BT - Principles of Bone Biology

PB - Elsevier

ER -

Hypophosphatasia: Nature’s window on alkaline phosphatase function in humans

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this