Galactose

d-Galactose
Haworth projection of
β-d-galactopyranose
Fischer projection of
d-galactose
Names
IUPAC names
Galactose
galacto-Hexose
Systematic IUPAC name
(2R,3S,4S,5R,6)-2,3,4,5,6-Pentahydroxyhexanal
Other names
Brain sugar
Identifiers
3D model (JSmol)
1724619
ChEBI
ChEMBL
ChemSpider
KEGG
MeSH Galactose
UNII
  • InChI=1S/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2−,3+,4+,5−,6+/m1/s1 checkY
    Key: WQZGKKKJIJFFOK-PHYPRBDBSA-N checkY
  • InChI=1/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2−,3+,4+,5−,6+/m1/s1
    Key: WQZGKKKJIJFFOK-PHYPRBDBBU
  • O[C@H]1[C@@H](O)[C@H](O[C@H](O)[C@@H]1O)CO
Properties
C6H12O6
Molar mass 180.156 g·mol−1
Appearance White solid
Odor Odorless
Density 1.5 g/cm3
Melting point 168–170 °C (334–338 °F; 441–443 K)
650 g/L (20 °C)
−103.00·10−6 cm3/mol
Pharmacology
V04CE01 (WHO) V08DA02 (WHO) (microparticles)
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
0
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X markN verify (what is checkYX markN ?)

Galactose (/ɡəˈlæktoʊs/, galacto- + -ose, sometimes abbreviated gal) is a common monosaccharide, i.e. a simple sugar. It is classified as a reducing hexose, more specifically an aldohexose. In terms of structure, it is a C-4 epimer of glucose. A white, water-soluble solid, it is about 80–90% as sweet as glucose and about 65% as sweet as sucrose.

Occurrence

Galactan is a polymeric form of galactose found in hemicellulose, and forming the core of the galactans, a class of natural polymeric carbohydrates.

D-galactose is also known as brain sugar since it is a component of glycoproteins (oligosaccharide-protein compounds) found in nerve tissue. Galactofuranose occurs in bacteria, fungi and protozoa, and is recognized by a putative chordate immune lectin intelectin through its exocyclic 1,2-diol.

Relationship to lactose

Galactose, when combined with glucose (another monosaccharide) through a condensation reaction, gives the disaccharide called lactose. The hydrolysis of lactose to glucose and galactose is catalyzed by the enzymes lactase and β-galactosidase. The latter is produced by the lac operon in Escherichia coli.

In nature, lactose is found primarily in milk and milk products. Consequently, various food products made with dairy-derived ingredients can contain lactose. Galactose is metabolised to glucose by the three principal enzymes in a mechanism known as the Leloir pathway. The enzymes are listed in the order of the metabolic pathway: galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT), and UDP-galactose 4′-epimerase (GALE).[citation needed]

In human lactation, galactose is required in a 1 to 1 ratio with glucose to enable the mammary glands to synthesize and secrete lactose. In a study where women were fed a diet containing galactose, 69 ± 6% of glucose and 54 ± 4% of galactose in the lactose they produced were derived directly from plasma glucose, while 7 ± 2% of the glucose and 12 ± 2% of the galactose in the lactose, were derived directly from plasma galactose. 25 ± 8% of the glucose and 35 ± 6% of the galactose was synthesized from smaller molecules in a process referred to in the paper as hexoneogenesis. This suggests that the synthesis of galactose is supplemented by direct uptake and the use of plasma galactose when present.

Structure and isomerism

Cyclic forms of galactose
Chair conformation of D-galactopyranose

Galactose exists in both open-chain and cyclic form. The open-chain form is an aldehyde (RCHO).

Four isomers are cyclic, two of them with a pyranose (six-membered) ring and two with a furanose (five-membered) ring. Each cyclic form can exist as two anomers, named alpha and beta, since a new stereocenter is generated upon cyclization at the site of the carbonyl. In the pyranose form, the OH group on C-3 is axial.

Metabolism

Galactose metabolism

Glucose is more stable than galactose and is less susceptible to the formation of nonspecific glycoconjugates, molecules with at least one sugar attached to a protein or lipid. Many speculate that it is for this reason that a pathway for rapid conversion from galactose to glucose has been highly conserved among many species.

The main pathway of galactose metabolism is the Leloir pathway; humans and other species, however, have been noted to contain several alternate pathways, such as the De Ley Doudoroff Pathway. The Leloir pathway consists of the latter stage of a two-part process that converts β-D-galactose to UDP-glucose. The initial stage is the conversion of β-D-galactose to α-D-galactose by the enzyme, mutarotase (GALM). The Leloir pathway then carries out the conversion of α-D-galactose to UDP-glucose via three principal enzymes: Galactokinase (GALK) phosphorylates α-D-galactose to galactose-1-phosphate, or Gal-1-P; Galactose-1-phosphate uridyltransferase (GALT) transfers a UMP group from UDP-glucose to Gal-1-P to form UDP-galactose; and finally, UDP galactose-4'-epimerase (GALE) interconverts UDP-galactose and UDP-glucose, thereby completing the pathway.

The above mechanisms for galactose metabolism are necessary because the human body cannot directly use galactose for energy metabolism, and it must first go through one of these processes.

Galactosemia is an inability to properly break down galactose due to a genetically inherited mutation in one of the enzymes in the Leloir pathway. As a result, the consumption of even small quantities is harmful to galactosemics.

Sources

Galactose is found in dairy products, avocados, sugar beets, other gums and mucilages. It is also synthesized by the body, where it forms part of glycolipids and glycoproteins in several tissues; and is a by-product from the third-generation ethanol production process (from macroalgae).[citation needed]

Clinical significance

Chronic systemic exposure of mice, rats, and Drosophila to D-galactose causes the acceleration of senescence (aging). It has been reported that high dose exposure of D-galactose (120 mg/kg) can cause reduced sperm concentration and sperm motility in rodents and has been extensively used as an aging model when administered subcutaneously. Two studies have suggested a possible link between galactose in milk and ovarian cancer. Other studies show no correlation, even in the presence of defective galactose metabolism. More recently, pooled analysis done by the Harvard School of Public Health showed no specific correlation between lactose-containing foods and ovarian cancer, and showed statistically insignificant increases in risk for consumption of lactose at 30 g/day. More research is necessary to ascertain possible risks.[citation needed]

Some ongoing studies suggest galactose may have a role in treatment of focal segmental glomerulosclerosis (a kidney disease resulting in kidney failure and proteinuria). This effect is likely to be a result of binding of galactose to FSGS factor.

Some studies have pointed out that Trypanosoma cruzi, the etiologic agent of Chagas disease, exhibits more resistance against hydrogen peroxide when galactose is used as a source of energy and carbons by this parasite.

Galactose is a component of the antigens (chemical markers) present on blood cells that distinguish blood type within the ABO blood group system. In O and A antigens, there are two monomers of galactose on the antigens, whereas in the B antigens there are three monomers of galactose.

A disaccharide composed of two units of galactose, galactose-alpha-1,3-galactose (alpha-gal), has been recognized as a potential allergen present in mammal meat. Alpha-gal allergy may be triggered by lone star tick bites.

Galactose in sodium saccharin solution has also been found to cause conditioned flavor avoidance in adult female rats within a laboratory setting when combined with intragastric injections. The reason for this flavor avoidance is still unknown. However, a decrease in the levels of the enzymes required to convert galactose to glucose in the liver of the rats could be responsible.

History

In 1855, E. O. Erdmann noted that hydrolysis of lactose produced a substance besides glucose.

Galactose was first isolated and studied by Louis Pasteur in 1856 and he called it "lactose". In 1860, Berthelot renamed it "galactose" or "glucose lactique". In 1894, Emil Fischer and Robert Morrell determined the configuration of galactose.

Etymology

The word galactose is derived from Greek γάλακτος, galaktos 'of milk', and the generic chemical suffix for sugars -ose. The etymology is comparable to that of the word lactose in that both contain roots meaning "milk sugar".

Spectroscopy

The IR spectra for galactose shows a broad, strong stretch from roughly wavenumber 2500 cm−1 to wavenumber 3700 cm−1.

The Proton NMR spectra for galactose includes peaks at 4.7 ppm (D2O), 4.15 ppm (−CH2OH), 3.75, 3.61, 3.48 and 3.20 ppm (−CH2 of ring), 2.79–1.90 ppm (−OH).

Further reading

See also

References

  1. ↑ "Appendix".
  2. 1 2 3 4 5 Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
  3. 1 2 Conte, Federica; Van Buuringen, Nicole; Voermans, Nicol C.; Lefeber, Dirk J. (2021). "Galactose in human metabolism, glycosylation and congenital metabolic diseases: Time for a closer look". Biochimica et Biophysica Acta (BBA) - General Subjects. 1865 (8) 129898. doi:10.1016/j.bbagen.2021.129898. hdl:2066/235637. PMID 33878388.
  4. ↑ Spillane WJ (2006-07-17). Optimising Sweet Taste in Foods. Woodhead Publishing. p. 264. ISBN 978-1-84569-164-6.
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  6. ↑ Nassau PM, Martin SL, Brown RE, Weston A, Monsey D, McNeil MR, et al. (February 1996). "Galactofuranose biosynthesis in Escherichia coli K-12: identification and cloning of UDP-galactopyranose mutase". Journal of Bacteriology. 178 (4): 1047–52. doi:10.1128/jb.178.4.1047-1052.1996. PMC 177764. PMID 8576037.
  7. ↑ Tefsen B, Ram AF, van Die I, Routier FH (April 2012). "Galactofuranose in eukaryotes: aspects of biosynthesis and functional impact". Glycobiology. 22 (4): 456–69. doi:10.1093/glycob/cwr144. PMID 21940757.
  8. ↑ Sanganeria, Tanisha; Bordoni, Bruno (2023), "Genetics, Inducible Operon", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 33232031, retrieved 2023-10-24
  9. ↑ Staff (June 2009). "Lactose Intolerance – National Digestive Diseases Information Clearinghouse". digestive.niddk.nih.gov. Archived from the original on November 25, 2011. Retrieved January 11, 2014.
  10. ↑ Sunehag A, Tigas S, Haymond MW (January 2003). "Contribution of plasma galactose and glucose to milk lactose synthesis during galactose ingestion". The Journal of Clinical Endocrinology and Metabolism. 88 (1): 225–9. doi:10.1210/jc.2002-020768. PMID 12519857.
  11. ↑ "Ophardt, C. Galactose". Archived from the original on 2006-09-08. Retrieved 2015-11-26.
  12. ↑ Fridovich-Keil JL, Walter JH. "Galactosemia". In Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM, Mitchell G (eds.). The Online Metabolic and Molecular Bases of Inherited Disease. Archived from the original on 2018-06-26. Retrieved 2018-06-25.
    a 4 b 21 c 22 d 22
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  18. ↑ Zhou YY, Ji XF, Fu JP, Zhu XJ, Li RH, Mu CK, et al. (2015-07-15). "Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose". PLOS ONE. 10 (7) e0132088. Bibcode:2015PLoSO..1032088Z. doi:10.1371/journal.pone.0132088. PMC 4503422. PMID 26176541.
  19. ↑ Cramer DW (November 1989). "Lactase persistence and milk consumption as determinants of ovarian cancer risk". American Journal of Epidemiology. 130 (5): 904–10. doi:10.1093/oxfordjournals.aje.a115423. PMID 2510499.
  20. ↑ Cramer DW, Harlow BL, Willett WC, Welch WR, Bell DA, Scully RE, Ng WG, Knapp RC (July 1989). "Galactose consumption and metabolism in relation to the risk of ovarian cancer". Lancet. 2 (8654): 66–71. doi:10.1016/S0140-6736(89)90313-9. PMID 2567871. S2CID 34304536.
  21. ↑ Goodman MT, Wu AH, Tung KH, McDuffie K, Cramer DW, Wilkens LR, et al. (October 2002). "Association of galactose-1-phosphate uridyltransferase activity and N314D genotype with the risk of ovarian cancer". American Journal of Epidemiology. 156 (8): 693–701. doi:10.1093/aje/kwf104. PMID 12370157.
  22. ↑ Fung WL, Risch H, McLaughlin J, Rosen B, Cole D, Vesprini D, Narod SA (July 2003). "The N314D polymorphism of galactose-1-phosphate uridyl transferase does not modify the risk of ovarian cancer". Cancer Epidemiology, Biomarkers & Prevention. 12 (7): 678–80. PMID 12869412.
  23. ↑ Genkinger JM, Hunter DJ, Spiegelman D, Anderson KE, Arslan A, Beeson WL, et al. (February 2006). "Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies". Cancer Epidemiology, Biomarkers & Prevention. 15 (2): 364–72. doi:10.1158/1055-9965.EPI-05-0484. PMID 16492930.
  24. ↑ De Smet E, Rioux JP, Ammann H, Déziel C, Quérin S (September 2009). "FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy". Nephrology, Dialysis, Transplantation. 24 (9): 2938–40. doi:10.1093/ndt/gfp278. PMID 19509024.
  25. ↑ McCarthy ET, Sharma M, Savin VJ (November 2010). "Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis". Clinical Journal of the American Society of Nephrology. 5 (11): 2115–21. doi:10.2215/CJN.03800609. PMID 20966123.
  26. ↑ Lobo-Rojas, Ángel; Quintero-Troconis, Ender; Rondón-Mercado, Rocío; Pérez-Aguilar., Mary Carmen; Concepción, Juan Luis; Cáceres, Ana Judith (2022-10-11). "Consumption of Galactose by Trypanosoma cruzi Epimastigotes Generates Resistance against Oxidative Stress". Pathogens. 11 (10): 1174. doi:10.3390/pathogens11101174. ISSN 2076-0817. PMC 9611177. PMID 36297231.
  27. ↑ Lobo-Rojas, Ángel E.; González-Marcano, Eglys B.; Valera-Vera, Edward A.; Acosta, Héctor R.; Quiñones, Wilfredo A.; Burchmore, Richard J.S.; Concepción, Juan L.; Cáceres, Ana J. (October 2016). "Trypanosoma cruzi contains two galactokinases; molecular and biochemical characterization". Parasitology International. 65 (5): 472–482. doi:10.1016/j.parint.2016.06.008. hdl:11336/83377. PMID 27312997.
  28. ↑ Raven PH, Johnson GB (1995). Mills CJ (ed.). Understanding Biology (3rd ed.). WM C. Brown. p. 203. ISBN 978-0-697-22213-8.
  29. ↑ "Alpha-gal syndrome - Symptoms and causes". Mayo Clinic. Retrieved 2022-02-25.
  30. 1 2 Sclafani, Anthony; Fanizza, Lawrence J; Azzara, Anthony V (1999-08-15). "Conditioned Flavor Avoidance, Preference, and Indifference Produced by Intragastric Infusions of Galactose, Glucose, and Fructose in Rats". Physiology & Behavior. 67 (2): 227–234. doi:10.1016/S0031-9384(99)00053-0. ISSN 0031-9384. PMID 10477054. S2CID 37225025.
  31. ↑ Erdmann EO (1855). Dissertatio de saccharo lactico et amylaceo [Dissertation on milk sugar and starch] (Thesis) (in Latin). University of Berlin.
  32. ↑ "Jahresbericht über die Fortschritte der reinen, pharmaceutischen und technischen Chemie" [Annual report on progress in pure, pharmaceutical, and technical chemistry] (in German). 1855. pp. 671–673. see especially p. 673.
  33. ↑ Pasteur L (1856). "Note sur le sucre de lait" [Note on milk sugar]. Comptes rendus (in French). 42: 347–351. From page 348: Je propose de le nommer lactose. (I propose to name it lactose.)
  34. ↑ Berthelot M (1860). "Chimie organique fondée sur la synthèse" [Organic chemistry based on synthesis]. Mallet-Bachelier (in French). 2. Paris, France: 248–249.
  35. ↑ "Galactose" — from the Ancient Greek γάλακτος (gálaktos, "milk").
  36. ↑ Fischer E, Morrell RS (1894). "Ueber die Configuration der Rhamnose und Galactose" [On the configuration of rhamnose and galactose]. Berichte der Deutschen Chemischen Gesellschaft zu Berlin (in German). 27: 382–394. doi:10.1002/cber.18940270177. The configuration of galactose appears on page 385.
  37. 1 2 Tunki, Lakshmi; Kulhari, Hitesh; Vadithe, Lakshma Nayak; Kuncha, Madhusudana; Bhargava, Suresh; Pooja, Deep; Sistla, Ramakrishna (2019-09-01). "Modulating the site-specific oral delivery of sorafenib using sugar-grafted nanoparticles for hepatocellular carcinoma treatment". European Journal of Pharmaceutical Sciences. 137 104978. doi:10.1016/j.ejps.2019.104978. ISSN 0928-0987. PMID 31254645. S2CID 195764874.