Galactosemia pathophysiology: Difference between revisions
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[[Abnormalities]] in any of the [[enzymes]] involved in each of the steps of the [[Leloir]] pathway can give rise to the [[pathological]] [[condition]] called [[galactosemia]]. | [[Abnormalities]] in any of the [[enzymes]] involved in each of the steps of the [[Leloir]] pathway can give rise to the [[pathological]] [[condition]] called [[galactosemia]]. | ||
* [[Deficiency]] or reduced activity of [[galactose-1-phosphate uridyl transferase]] [[enzyme]] leads to accumulation of [[galactose-1-phosphate]] <ref name="pmidhttp://dx.doi.org/10.1590/2326-4594-jiems-2021-002">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=http://dx.doi.org/10.1590/2326-4594-jiems-2021-002 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref> which: | * [[Deficiency]] or reduced activity of [[galactose-1-phosphate uridyl transferase]] [[enzyme]] leads to accumulation of [[galactose-1-phosphate]] <ref name="pmidhttp://dx.doi.org/10.1590/2326-4594-jiems-2021-002">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=http://dx.doi.org/10.1590/2326-4594-jiems-2021-002 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref> which: | ||
** Sequesters [[phosphate]] essential for [[energy]] production in the human body | ** Sequesters [[phosphate]] essential for [[energy]] production in the human body <ref name="pmid7671964">{{cite journal| author=Gitzelmann R| title=Galactose-1-phosphate in the pathophysiology of galactosemia. | journal=Eur J Pediatr | year= 1995 | volume= 154 | issue= 7 Suppl 2 | pages= S45-9 | pmid=7671964 | doi=10.1007/BF02143803 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7671964 }} </ref> | ||
**Inhibits [[enzymes]] involved in [[glucose]] [[metabolism]], such as [[pyrophosphorylase]] <ref name="pmid12626383">{{cite journal| author=Lai K, Langley SD, Khwaja FW, Schmitt EW, Elsas LJ| title=GALT deficiency causes UDP-hexose deficit in human galactosemic cells. | journal=Glycobiology | year= 2003 | volume= 13 | issue= 4 | pages= 285-94 | pmid=12626383 | doi=10.1093/glycob/cwg033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12626383 }} </ref> | **Inhibits [[enzymes]] involved in [[glucose]] [[metabolism]], such as [[pyrophosphorylase]] <ref name="pmid12626383">{{cite journal| author=Lai K, Langley SD, Khwaja FW, Schmitt EW, Elsas LJ| title=GALT deficiency causes UDP-hexose deficit in human galactosemic cells. | journal=Glycobiology | year= 2003 | volume= 13 | issue= 4 | pages= 285-94 | pmid=12626383 | doi=10.1093/glycob/cwg033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12626383 }} </ref> | ||
**Inhibits [[galactosyl trasnferase]] thereby leading to defects in [[glycosylation]] <ref name="pmid25174965">{{cite journal| author=Coss KP, Treacy EP, Cotter EJ, Knerr I, Murray DW, Shin YS | display-authors=etal| title=Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism? | journal=Mol Genet Metab | year= 2014 | volume= 113 | issue= 3 | pages= 177-87 | pmid=25174965 | doi=10.1016/j.ymgme.2014.08.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174965 }} </ref> | **Inhibits [[galactosyl trasnferase]] thereby leading to defects in [[glycosylation]] <ref name="pmid25174965">{{cite journal| author=Coss KP, Treacy EP, Cotter EJ, Knerr I, Murray DW, Shin YS | display-authors=etal| title=Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism? | journal=Mol Genet Metab | year= 2014 | volume= 113 | issue= 3 | pages= 177-87 | pmid=25174965 | doi=10.1016/j.ymgme.2014.08.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174965 }} </ref> | ||
Revision as of 13:14, 11 May 2022
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Galactosemia Microchapters |
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Galactosemia pathophysiology On the Web |
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Risk calculators and risk factors for Galactosemia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dayana Davidis, M.D. [2]
Overview
Pathophysiology
- Galactose is an important metabolite of the human body both for neonatal and adult health, playing a vital role in systemic and cognitive development. [1]
Physiology
Galactose is metabolised in the body through the Leloir pathway. [2]
- It begins with conversion of B-D-galactose] to A-D-galactose
- A-D-galactose is then converted to galactose-1-phosphate by the enzyme galactokinase with utilisation of 1 molecule of ATP
- Galactose-1-phosphate combines with UDP-glucose to form UDP-galactose and the metabolically more useful glucose-1-phosphate with the help of the enzyme galactose-1-phosphate uridyl transferase.
- UDP-Galactose can undergo isomerisation in a reversible manner into UDP-glucose.
Pathology
Abnormalities in any of the enzymes involved in each of the steps of the Leloir pathway can give rise to the pathological condition called galactosemia.
- Deficiency or reduced activity of galactose-1-phosphate uridyl transferase enzyme leads to accumulation of galactose-1-phosphate [3] which:
- Sequesters phosphate essential for energy production in the human body [4]
- Inhibits enzymes involved in glucose metabolism, such as pyrophosphorylase [5]
- Inhibits galactosyl trasnferase thereby leading to defects in glycosylation [6]
References
- ↑ Coelho AI, Berry GT, Rubio-Gozalbo ME (2015). "Galactose metabolism and health". Curr Opin Clin Nutr Metab Care. 18 (4): 422–7. doi:10.1097/MCO.0000000000000189. PMID 26001656.
- ↑ Holden HM, Rayment I, Thoden JB (2003). "Structure and function of enzymes of the Leloir pathway for galactose metabolism". J Biol Chem. 278 (45): 43885–8. doi:10.1074/jbc.R300025200. PMID 12923184.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1590/2326-4594-jiems-2021-002 Check
|pmid=value (help). - ↑ Gitzelmann R (1995). "Galactose-1-phosphate in the pathophysiology of galactosemia". Eur J Pediatr. 154 (7 Suppl 2): S45–9. doi:10.1007/BF02143803. PMID 7671964.
- ↑ Lai K, Langley SD, Khwaja FW, Schmitt EW, Elsas LJ (2003). "GALT deficiency causes UDP-hexose deficit in human galactosemic cells". Glycobiology. 13 (4): 285–94. doi:10.1093/glycob/cwg033. PMID 12626383.
- ↑ Coss KP, Treacy EP, Cotter EJ, Knerr I, Murray DW, Shin YS; et al. (2014). "Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?". Mol Genet Metab. 113 (3): 177–87. doi:10.1016/j.ymgme.2014.08.004. PMID 25174965.