Galactose

Identification

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Name
Galactose
Accession Number
DB11735
Type
Small Molecule
Groups
Approved, Investigational
Description

Galactose has been used in trials studying the treatment and diagnosis of Hepatitis C, Hepatic Cancer, Wilsons Disease, Diabetic Macular Oedema, and Focal Segmental Glomerulosclerosis, among others. There are even proposals for its use in accelerating senescence in mice, rats, and Drosophila, for its association with ovarian cancer, or even for the potential treatment of focal segmental glomerulosclerosis. Nevertheless, none of these ongoing studies have yet provided formal elucidation for their proposals.

As a naturally occurring sugar, it may be found in a number dairy products. Even then, however, it is not generally used as a sweetener considering it is only about 30% as sweet as sucrose. Regardless, although it is predominantly used as a pathway to generate glucose fuel for the human body, galactose is involved as an ingredient in some commonly used vaccines and non-prescription products.

Structure
Thumb
Synonyms
  • D-Galactose
  • D(+)-Galactose
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EchovistGalactose (13.5 ml) + Galactose (3 g)Kit; Powder, for suspensionIntrauterineBerlex Laboratories, Inc.1999-02-152004-02-12Canada
EchovistGalactose (13.5 ml) + Galactose (3 g)Kit; Powder, for suspensionIntrauterineBerlex Laboratories, Inc.1999-02-152004-02-12Canada
Levovist - Pws IV (4g Granules /vial)Galactose (999 mg) + Palmitic Acid (1 mg)Powder, for solutionIntravenousBerlex Laboratories, Inc.1997-12-192003-06-26Canada
Categories
UNII
X2RN3Q8DNE
CAS number
59-23-4
Weight
Average: 180.1559
Monoisotopic: 180.063388116
Chemical Formula
C6H12O6
InChI Key
GZCGUPFRVQAUEE-KCDKBNATSA-N
InChI
InChI=1S/C6H12O6/c7-1-3(9)5(11)6(12)4(10)2-8/h1,3-6,8-12H,2H2/t3-,4+,5+,6-/m0/s1
IUPAC Name
(2R,3S,4S,5R)-2,3,4,5,6-pentahydroxyhexanal
SMILES
[H]C(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO

Pharmacology

Indication

There are limited therapeutic uses for which galactose is formally indicated. Some predominant indications include (a) the use of galactose to facilitate the construction of structurally and immunologically effective attenuated vaccines 12,14, and (b) the role galactose plays as an essential element in the formation of lactulose - a synthetic disaccharide indicated for the treatment of constipation and/or hepatic encephalopathy (HE); hepatic coma 13.

Nevertheless, there are many studies looking into a variety of possible uses for galactose, including the use of the monosaccharide sugar for accelerating senescence in mice, rats, and Drosophila 1,2, the proposed association between galactose in consumed milk and ovarian cancer 3,4, a possible role in the therapy of focal segmental glomerulosclerosis 5, among various others. Regardless, none of these proposed indications have yet been formally elucidated for practical use.

Pharmacodynamics

Galactose is a naturally occurring monosaccharide that forms the disaccharide lactose when combined with glucose (another monosaccharide) 6. Subsequently, when lactose or small amounts of free galactose found in various common dairy products (and other foods) are consumed, the hydrolysis of lactose to glucose and galactose occurs and galactose is itself further metabolized to generate glucose 6. Such glucose is, of course, ultimately relied upon and used as the primary metabolic fuel for humans in a variety of biological reactions.

Conversely, however, the ways in which galactose is commonly used in therapeutic agents generally do not rely upon such pharmacodynamics, even though they ultimately remain the most important ways in which galactose exerts or elicits useful biological actions for the human body.

Mechanism of action

In the development of typhoid Ty21a live oral vaccine, the use of exogenous galactose is critical. When dealing with Salmonella typhimurium, it has been shown that rough strains with incomplete lipopolysaccharide (LPS) lacking O-specific side chains are much less virulent than smooth strains with complete LPS with O-specific side chains 12. Salmonella typhimurium gal E mutants used to produce the vaccine are effectively avirulent and highly protective but lack the specific UDP-galactose 4-epimerase enzyme which allows for the normal synthesis of UDP-galactose from UDP-glucose 12. The consequence of this mutant defect is that the gal E mutants can only generate incomplete LPS without O-specific antigen side chains, which are not capable enough as the complete LPS with O-specific side chains at generating an immunologic response 12. When exogenous galactose is added to the vaccine medium, however, it allows the mutants to generate UDP-galactose via galactose 1-phosphate 12. This ultimately allows the mutants to form smooth-type LPS with O-specific side chains 12. Regardless, the mutant's epimerase defect ultimately results in the accumulation of such intermediary products like galactose 1-phosphate and UDP-galactose, which consequently causes lysis of the mutant cells. The resultant vaccine is subsequently effective enough to elicit an immunologic response while the bacteriolysis prevents the mutant cells from regaining virulence under conditions where smooth type LPS similar to the active parental strain is synthesized 12.

Galactose is also an essential element to the chemical structure of the commonly used laxative solution lactulose. Lactulose itself is a synthetic disaccharide that is made in parts from lactose, galactose, and various other sugars 15. It is poorly absorbed from the gastrointestinal tract and no enzyme capable of hydrolysis of lactulose is present in human gastrointestinal tissue 15. Oral doses of lactulose subsequently arrive at the colon largely unchanged 15. At the colon, lactulose is finally broken down predominantly to lactic acid, and also small amounts of formic and acetic acids by the action of colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents 15. This action consequently causes an increase in stool water content and softens the stool for a laxative effect 15.

Absorption

The absorption of galactose from the human jejunum was calculated to be 1.0 g per minute per 30 cm of the gut 7.

Volume of distribution

It has been documented that galactose distributes in a volume equivalent to 40% of body weight 8.

Protein binding

Readily accessible data regarding the protein binding of galactose is not available.

Metabolism

The primary pathway for galactose metabolism is called the Leloir pathway, so named after Luis Federico Leloir. The initial stage of this pathway is the conversion of beta-D-galactose to alpha-D-galactose by the enzyme galactose mutarotase (GALM) 6. The pathway then performs the conversion of alpha-D-galactose to UDP-glucose by way of three principal enzymes and their reactions: galactokinase (GALK) phosphorylates alpha-D-galactose to galactose-1-phosphate (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, which completes the pathway 6.

Route of elimination

The primary route of elimination for galactose is hepatic 14,6.

Half life

Readily accessible data regarding the half-life of galactose is not available.

Clearance

In subjects with no liver disease, systemic galactose clearance was calculated to be 1.5 +/- 0.1 L/min 9.

Toxicity

It is typically uncommon to experience an overdosage situation with dietary galactose or from galactose as an ingredient in a therapeutic agent. At the same time, the experiencing a situation characterized by excessive amounts of galactose in the body defines the challenge with galactosemia, which is itself a rare genetic metabolic disorder. In individuals with galactosemia, the enzymes needed for further metabolism of galactose (ie. such as galactose-1-phosphate uridyltransferase) are severely diminished or missing entirely, leading to toxic levels of galactose 1-phosphate in various tissues 10. This toxic excess typically results in hepatomegaly, cirrhosis, renal failure, cataracts, vomiting, hypoglycemia, lethargy, brain damage, and ovarian failure 10. Without treatment, mortality in infants with galactosemia is about 75% 11.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Pourmemar E, Majdi A, Haramshahi M, Talebi M, Karimi P, Sadigh-Eteghad S: Intranasal Cerebrolysin Attenuates Learning and Memory Impairments in D-galactose-Induced Senescence in Mice. Exp Gerontol. 2017 Jan;87(Pt A):16-22. doi: 10.1016/j.exger.2016.11.011. Epub 2016 Nov 25. [PubMed:27894939]
  2. Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, Packer L, Liu J: Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. J Neurosci Res. 2006 Aug 15;84(3):647-54. doi: 10.1002/jnr.20899. [PubMed:16710848]
  3. Cramer DW: Lactase persistence and milk consumption as determinants of ovarian cancer risk. Am J Epidemiol. 1989 Nov;130(5):904-10. [PubMed:2510499]
  4. Cramer DW, Harlow BL, Willett WC, Welch WR, Bell DA, Scully RE, Ng WG, Knapp RC: Galactose consumption and metabolism in relation to the risk of ovarian cancer. Lancet. 1989 Jul 8;2(8654):66-71. [PubMed:2567871]
  5. Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M: Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl Res. 2008 Jun;151(6):288-92. doi: 10.1016/j.trsl.2008.04.001. Epub 2008 May 2. [PubMed:18514139]
  6. Sunehag A, Tigas S, Haymond MW: Contribution of plasma galactose and glucose to milk lactose synthesis during galactose ingestion. J Clin Endocrinol Metab. 2003 Jan;88(1):225-9. doi: 10.1210/jc.2002-020768. [PubMed:12519857]
  7. HOLDSWORTH CD, DAWSON AM: THE ABSORPTION OF MONOSACCHARIDES IN MAN. Clin Sci. 1964 Dec;27:371-9. [PubMed:14236773]
  8. WICK AN, DRURY DR: Action of insulin on volume of distribution of galactose in the body. Am J Physiol. 1953 May;173(2):229-32. doi: 10.1152/ajplegacy.1953.173.2.229. [PubMed:13065433]
  9. Keiding S: Galactose clearance measurements and liver blood flow. Gastroenterology. 1988 Feb;94(2):477-81. [PubMed:3335319]
  10. Leslie ND: Insights into the pathogenesis of galactosemia. Annu Rev Nutr. 2003;23:59-80. doi: 10.1146/annurev.nutr.23.011702.073135. Epub 2003 Apr 9. [PubMed:12704219]
  11. Karadag N, Zenciroglu A, Eminoglu FT, Dilli D, Karagol BS, Kundak A, Dursun A, Hakan N, Okumus N: Literature review and outcome of classic galactosemia diagnosed in the neonatal period. Clin Lab. 2013;59(9-10):1139-46. [PubMed:24273939]
  12. Rene Germanier (2012). Bacterial Vaccines. Academic Press. [ISBN:0323140211]
  13. Electronic Medicines Compendium: Duphalac (lactulose) monograph [Link]
  14. ScienceDirect: Galactose Profile [Link]
  15. Lactulose Solution USP Label [File]
External Links
PubChem Compound
3037556
PubChem Substance
347828093
ChemSpider
2301265
ChEBI
17118
Wikipedia
Galactose
ATC Codes
V08DA02 — Microparticles of galactoseV04CE01 — Galactose
MSDS
Download (38.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentGlomerulosclerosis, Focal Segmental1
1WithdrawnTreatmentGlomerulosclerosis, Focal Segmental1
2CompletedTreatmentGlomerulosclerosis, Focal Segmental1
4WithdrawnTreatmentHepatic neoplasms malignant1
Not AvailableActive Not RecruitingNot AvailableHepatitis C Viral Infection1
Not AvailableCompletedTreatmentGlomerulosclerosis, Focal Segmental / Steroid Resistant Nephrotic Syndrome1
Not AvailableRecruitingDiagnosticWilsons Disease1
Not AvailableTerminatedTreatmentDiabetic Macular Edema (DME)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit; powder, for suspensionIntrauterine
Powder, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility261.0 mg/mLALOGPS
logP-2.4ALOGPS
logP-3.6ChemAxon
logS0.16ALOGPS
pKa (Strongest Acidic)12.26ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area118.22 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity37.35 m3·mol-1ChemAxon
Polarizability16.13 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (1 MEOX; 5 TMS)GC-MSsplash10-066r-1963000000-20f964d19542821e3092
GC-MS Spectrum - GC-MS (1 MEOX; 5 TMS)GC-MSsplash10-066r-1963000000-9b4d2187359e4427fc63
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hexoses. These are monosaccharides in which the sugar unit is a is a six-carbon containing moeity.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Hexoses
Alternative Parents
Medium-chain aldehydes / Beta-hydroxy aldehydes / Alpha-hydroxyaldehydes / Secondary alcohols / Polyols / Primary alcohols / Organic oxides / Hydrocarbon derivatives
Substituents
Hexose monosaccharide / Medium-chain aldehyde / Beta-hydroxy aldehyde / Alpha-hydroxyaldehyde / Secondary alcohol / Polyol / Organic oxide / Hydrocarbon derivative / Primary alcohol / Carbonyl group
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
aldehydo-galactose, D-galactose (CHEBI:17118)

Drug created on October 20, 2016 14:43 / Updated on June 04, 2019 07:26