Galactosemia pathophysiology: Difference between revisions
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**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> | ||
* [[Galactokinase]] [[deficiency]] results in accumulation of [[galactose]] which gets converted to [[galactitol]] by a minor pathway. This molecule predisposes to [[cataract]] by causing: | * [[Galactokinase]] [[deficiency]] results in accumulation of [[galactose]] which gets converted to [[galactitol]] by a minor pathway.<ref name="pmid14624333">{{cite journal| author=Fekete E, Karaffa L, Sándor E, Bányai I, Seiboth B, Gyémánt G | display-authors=etal| title=The alternative D-galactose degrading pathway of Aspergillus nidulans proceeds via L-sorbose. | journal=Arch Microbiol | year= 2004 | volume= 181 | issue= 1 | pages= 35-44 | pmid=14624333 | doi=10.1007/s00203-003-0622-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14624333 }} </ref> This molecule predisposes to [[cataract]] by causing: | ||
**Swelling of the [[lens]] | **Swelling of the [[lens]] | ||
**[[Denaturation]] of the [[proteins]] | **[[Denaturation]] of the [[proteins]] | ||
Revision as of 13:28, 11 May 2022
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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]
- Galactokinase deficiency results in accumulation of galactose which gets converted to galactitol by a minor pathway.[7] This molecule predisposes to cataract by causing:
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.
- ↑ Fekete E, Karaffa L, Sándor E, Bányai I, Seiboth B, Gyémánt G; et al. (2004). "The alternative D-galactose degrading pathway of Aspergillus nidulans proceeds via L-sorbose". Arch Microbiol. 181 (1): 35–44. doi:10.1007/s00203-003-0622-8. PMID 14624333.
- ↑ "StatPearls". 2022. PMID 32809518 Check
|pmid=value (help).