GNPDA2 ( 4p12), GNP2, SB52. eräs obesitakselle altistava geeni, BMI-vaikutuksellinen.

Hexosaminibiosynteesi-järejstelmään kuuluvia  geenejä:

GNPDA1 GlcN-6P deaminaasi 1
GNPDA2, GlcN-6P deaminaasi 2
GFAT1, glutamiini--fru6P- aminotaransferaasi 1
GFAT2, glutamiini-fru6P- aminotransferaasi2
 HAS2 , hyaluronaanisyntaasi2

https://www.ncbi.nlm.nih.gov/gene/132789

Tämän geenin nimi on  GNPD2, glukosamini-6-fosfaattideaminaasi 2. 
Muita nimiä o GNP2, SB52. 

Proteiini, jonka tämä geeni on koodannut,  on allosteerinen entsyymi, joka katalysoi käänteistä reaktiota muuttaen D-glukosamini-6 -fosfaatin D- fruktoosi-6-fosfaatiksi ja ammoniumiksi. Tämän geenin variaatioita  on raportoitu assosioituneen BMI-vaikutukseen ja alttiuteen liikalihavuudelle.  Pseudogeeni on kromosomissa 9. Alternativiset pleissaustuotteet  johtavat moniin transskripteihin, jotka koodaavat eri proteiini-isoformeja.  Geeniä ilmenee ovariossa, kilpirauhasessa ja 25 muussa kudoksessa.

• GNPDA2 glucosamine-6-phosphate deaminase 2 [ Homo sapiens (human) ]

• Gene ID: 132789, updated on 2-Oct-2018

• Also known as GNP2; SB52

Summary. The protein encoded by this gene is an allosteric enzyme that catalyzes the reversible reaction converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Variations of this gene have been reported to be associated with influencing body mass index and susceptibility to obesity. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

Expression. Ubiquitous expression in ovary (RPKM 8.8), thyroid (RPKM 8.8) and 25 other tissues See more Orthologs  mouse all

Related articles in PubMed

1. Genetic susceptibility, birth weight and obesity risk in young Chinese. Hong J, et al. Int J Obes (Lond), 2013 May. PMID 22710927
2. Susceptibility variants for obesity and colorectal cancer risk: the multiethnic cohort and PAGE studies. Lim U, et al. Int J Cancer, 2012 Sep 15. PMID 22511254, Free PMC Article
3. Adult obesity susceptibility variants are associated with greater childhood weight gain and a faster tempo of growth: the 1946 British Birth Cohort Study. Elks CE, et al. Am J Clin Nutr, 2012 May. PMID 22456663, Free PMC Article
4. Genetic risk score does not correlate with body mass index of Latina women in a clinical trial. Coenen KR, et al. Clin Transl Sci, 2011 Oct. PMID 22029802, Free PMC Article
5. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants. Sandholt CH, et al. PLoS One, 2011. PMID 21912638, Free PMC Article Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI.

See all (56) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. GNPDA1 siRNA induced GFAT2 which was hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increased GFAT1, and GFAT1 siRNA increased the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulated GNPDA1 and GDPDA2, and inhibited cell migration.
2. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
3. Data show that SNPs in SEC16B and TMEM18 were significantly associated with obesity, and the SNPs in GNPDA2, BDNF, FAIM2 and MC4R were marginally associated with obesity in Japanese.
4. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
5. Observational study of gene-disease association. (HuGE Navigator)
6. Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)

Submit: New GeneRIF Correction

• Glycobiology. 2016 Jul;26(7):710-22. doi: 10.1093/glycob/cww019. Epub 2016 Feb 16.

• Hexosamine biosynthesis in keratinocytes: roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis. Oikari S¹, Makkonen K², Deen AJ³, Tyni I³, Kärnä R³, Tammi RH³, Tammi MI³. Abstract

• UDP-N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a key substrate for the synthesis of glycoconjugates like hyaluronan, and as a metabolic sensor that controls cell functions through O-GlcNAc modification of intracellular proteins. However, little is known about the regulation of hexosamine biosynthesis that controls UDP-GlcNAc content. Four enzymes can catalyze the crucial starting point of the pathway, conversion of fructose-6-phosphate (Fru6P) to glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2). Using siRNA silencing, we studied the contributions of these enzymes to UDP-GlcNAc content and hyaluronan synthesis in human keratinocytes. Depletion of GFAT1 reduced the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both GNPDA1 and GDPDA2 exerted opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyzed the reaction from GlcN6P back to Fru6P. However, when hexosamine biosynthesis was blocked by GFAT1 siRNA, the effect by GNPDAs was reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDP-GlcNAc content. Silencing of these enzymes also changed the gene expression of related enzymes: GNPDA1 siRNA induced GFAT2 which was hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increased GFAT1, and GFAT1 siRNA increased the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulated GNPDA1 and GDPDA2, and inhibited cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer. KEYWORDS:  GFAT; GNPDA; UDP-N-acetylglucosamine; hexosamine biosynthesis; hyaluronan

 

Lancet diabeteksesta Diabeteksen lisääntymisestä ja esiintymisprofiilin muuntumisesta

With over 400 million people living with the disease and accounting for around 90% of diabetes cases worldwide, type 2 diabetes is complex and costly. It can cause blindness, cardiovascular disease, kidney failure, lower limb amputation, and other long-term consequences that substantially impact quality of life and years of life lived with disability. Worryingly, the global prevalence of type 2 diabetes is estimated to have doubled over the past 30 years and now includes rapidly rising numbers of children and adolescents. The condition is much more complex in young people, who have a higher overall risk of life-time complications with much earlier onset. Up until 2002, type 2 diabetes was not considered a paediatric condition; today, there are an estimated 3600 children and young adults diagnosed with the condition each year in the USA. In the UK, nearly 7000 cases were reported in 2018, as noted by Diabetes UK on Nov 21. Disturbingly, this trend is reflected internationally.

Recognising the shift in type 2 diabetes prevalence toward increasingly younger populations, on Nov 13, the American Diabetes Association (ADA) published new guidelines for the assessment and management of youth-onset type 2 diabetes. Young people with type 2 diabetes have a more aggressive form of the disease—including poorer response to glucose-lowering medication and greater insulin resistance. However, given evidence that young people with type 2 diabetes are less likely to become hypoglycaemic when treated with oral agents alone, the new guidelines recommend more stringent HbA1c targets than previously, and lower than those generally recommended for adults. The guidelines prioritise lifestyle management tailored to the patients and their families, as most children with type 2 diabetes also have obesity. These recommendations take into account the developmental growth stage of the child. Importantly, mental health and cultural aspects are also considered, as obesity is often associated with discrimination and stigma, and cultural norms can affect diet and lifestyle.

Although the ADA guidelines will be helpful for practising clinicians, there are still many knowledge gaps. For example, there is not enough evidence on the benefits of interventions such as metabolic surgery, intensive physical activity, and educational support programmes in young patients. Moreover, the only glucose-lowering drug other than insulin approved for patients younger than 18 years is metformin. Other therapies, such as SGLT2 inhibitors and GLP-1 receptor agonists, which are associated with cardiovascular and renal protection in adults, have not been approved for children or adolescents. Finally, there is the issue of screening and early detection of type 2 diabetes in this age group. Approaches to screen and diagnose adults who are at risk have not been thoroughly validated in young people. There is an urgent need to include young patients in future research to develop and inform strategies targeted at prevention and treatment of type 2 diabetes.

Type 2 diabetes is a progressive disease, meaning that treatment intensification, with insulin being a last resort, is required over time in a substantial proportion of patients. For patients with early-onset disease, this is more likely to be needed earlier in life. Even by prioritising lifestyle treatments and new-generation drugs, insulin will maintain a central place in the treatment of many patients with type 2 diabetes. With this fast expanding population of people who will have diabetes for longer, an increase in the demand for insulin is inevitable. According to the results of a modelling study published last week in The Lancet Diabetes & Endocrinology, it is expected that 20% more insulin will be required to treat the global type 2 diabetes population by 2030. A key concern highlighted by this study is that availability and affordability of insulin are already inadequate in low-income and middle-income countries.

The primary risk factor for development of type 2 diabetes across all ages is obesity, which is largely preventable starting early in life. Some countries have already taken steps to tackle obesity by introducing sugar taxes and reducing exposure of children to unhealthy food advertisements. Despite these positive approaches, much more needs to be done as a matter of urgency. Diabetes is a global public health problem and can only be tackled with a concerted action to develop effective prevention strategies. Surely children and adolescents cannot be held responsible for living in obesogenic environments. If the growing prevalence of obesity and type 2 diabetes in youth is accepted as the new normal, society will have grossly failed the next generation.

Suolistofloranmerkitys galaktoosin suhteen - laktoosipitoisen ravinnon muokkaus

Lactococcus  Lactis  ja galaktoosin  vähentäminen vähälaktoosisista tuotteista .
Ajatuksia pohdittavaksi.
Kun liian laktoosipitoisuuden ongelmasta on päästy, tulee sekundääriongelmaksi galaktoosin liian korkeat pitoisuudet käsitellyssä  meijerituotteessa.  Tässä artikkelissa pureudutaan  tähän ongelmaan: miten vähentää galaktoosin liian korkeita määriä laktoosiredusoiduissa elintarvikkeissa?  Tämä on harvan ongelmana, koska tietoisuus galaktoosin määrän noususta  laktoosin fermentaation tuloksena ei ole mitenkään yleistietoa. Toisaalta ei myöskään ole vaatimusta  galaktoosipitoisuuden ilmoittamisesta elintarvikkeessa.  Kolmanneksi galaktoosin varoista on hämärät käsitykset. neljänneksi tavataan sanoa, että galaktoosi ei ole essentielli molekyyli, mitä pitäisi tarkemmin ilmoittaa  taulukoissa,  johtuu luonnollisesti siitä, että ruoassa yleensä on galaktoosia, eikä siitä etteikö se voisi olla  essentielle.  Se on kai niin tärkeä ja joka puolella,  että se on "näkymätön".  se ei maistu sokerina kuten sakkaroosi ja glukoosi heti kun niitä syödään, vaan se on  "se jokin" karamellisoituneissa  herkullisissa leivonnaisissa ja muissa  hyvissä, joista  ei voi luopua. Galaktoosin tarve kehossa on  alitajuista  astetta.
 Täytyy vain toivoa että suoliston  maitobakteerit ovat sitä sorttia jotka hajoittavat  runsaan liiallisen galaktoosin  tarpeeksi pitkälle lopputuotteiksi asti, joita ihminen voi haitatta  saada tallennettua.

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976262/

Abstract

Accumulation of galactose in dairy products due to partial lactose fermentation by lactic acid bacteria yields poor-quality products and precludes their consumption by individuals suffering from galactosemia.

 This study aimed at extending our knowledge of galactose metabolism in Lactococcus lactis, with the final goal of tailoring strains for enhanced galactose consumption. We used directed genetically engineered strains to examine galactose utilization in strain NZ9000 via the chromosomal Leloir pathway (gal genes) or the plasmid-encoded tagatose 6-phosphate (Tag6P) pathway (lac genes). Galactokinase (GalK), but not galactose permease (GalP), is essential for growth on galactose. This finding led to the discovery of an alternative route, comprising a galactose phosphotransferase system (PTS) and a phosphatase, for galactose dissimilation in NZ9000. Introduction of the Tag6P pathway in a galPMK mutant restored the ability to metabolize galactose but did not sustain growth on this sugar. The latter strain was used to prove that lacFE, encoding the lactose PTS, is necessary for galactose metabolism, thus implicating this transporter in galactose uptake. Both PTS transporters have a low affinity for galactose, while GalP displays a high affinity for the sugar. Furthermore, the GalP/Leloir route supported the highest galactose consumption rate. To further increase this rate, we overexpressed galPMKT, but this led to a substantial accumulation of α-galactose 1-phosphate and α-glucose 1-phosphate, pointing to a bottleneck at the level of α-phosphoglucomutase. Overexpression of a gene encoding α-phosphoglucomutase alone or in combination with gal genes yielded strains with galactose consumption rates enhanced up to 50% relative to that of NZ9000. Approaches to further improve galactose metabolism are discussed.

 Lactococcus lactis is a lactic acid bacterium widely used in the dairy industry for the production of fermented milk products. Because of its economic importance, L. lactis has been studied extensively in the last 40 years. A small genome, a large set of genetic tools, a wealth of physiological knowledge, and a relatively simple metabolic potential render L. lactis an attractive model with which to implement metabolic engineering strategies (reviewed in references 21 and 57).

 In the process of milk fermentation by L. lactis, lactose is taken up and concomitantly 

phosphorylated at the galactose moiety (C-6) by the lactose-specific phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS^Lac), after which it is hydrolyzed to glucose and galactose 6-phosphate (Gal6P) (64). The glucose moiety enters the glycolytic pathway upon phosphorylation via glucokinase to glucose 6-phosphate (G6P), whereas Gal6P is metabolized to triose phosphates via the d-tagatose 6-phosphate (Tag6P) pathway, encompassing the steps catalyzed by galactose 6-phosphate isomerase (LacAB), Tag6P kinase (LacC), and tagatose 1,6-bisphosphate aldolase (LacD) (Fig. ​(Fig.1).1). Curiously, during the metabolism of lactose by L. lactis, part of the Gal6P is dephosphorylated and excreted into the growth medium, while the glucose moiety is readily used (2, 7, 51, 56, 60).

---

FIG. 1.

Schematic overview of the alternative routes for galactose uptake and further catabolism in L. lactis. Galactose can be imported by the non-PTS permease GalP and metabolized via the Leloir pathway (galMKTE) to α-G1P, which is converted to the glycolytic intermediate G6P by α-phosphoglucomutase (pgmH). Alternatively, galactose can be imported by PTS^Lac (lacFE) and further metabolized to triose phosphates by the Tag6P pathway (lacABCD). Here, we propose a new uptake route consisting of galactose translocation via the galactose PTS, followed by dephosphorylation of the internalized Gal6P to galactose, which is further metabolized via the Leloir pathway (highlighted in the gray box). galP, galactose permease; galM, galactose mutarotase; galK, galactokinase; galT, galactose 1-phosphate uridylyltransferase; galE, UDP-galactose-4-epimerase; pgmH, α-phosphoglucomutase; lacAB, galactose 6-phosphate isomerase; lacC, Tag6P kinase; lacD, tagatose 1,6-bisphosphate aldolase; lacFE, PTS^Lac; PTS^Gal, unidentified galactose PTS; Phosphatase; unidentified Gal6P-phosphatase; pgi, phosphoglucose isomerase; pfk, 6-phosphofructo-1-kinase; fba, fructose 1,6-bisphosphate aldolase; tpi, triose phosphate isomerase; α-Gal1P, α-galactose 1-phosphate; α-G1P, α-glucose 1-phosphate; UDP-gal, UDP-galactose; UDP-glc, UDP-glucose; G6P, glucose 6-phosphate; Gal6P, galactose 6-phosphate; Tag6P, tagatose 6-phosphate; TBP, tagatose 1,6-bisphosphate; FBP, fructose 1,6-bisphosphate; DHAP, dihydroxyacetone phosphate; GAP, glyceraldehyde 3-phosphate. The dotted arrow represents the conversions of GAP to pyruvate via the glycolytic pathway. Steps essential to improve galactose consumption are shown in black boxes.

 As a result of incomplete lactose utilization, some fermented dairy products contain significant residual amounts of galactose. The presence of galactose has been associated with shoddier qualities of the fermented product (6, 27, 43). In particular, galactose is a major contributor to the browning that occurs when dairy products (e.g., yogurt and mozzarella, Swiss, and cheddar cheese) are cooked or heated in the manufacture of pizzas, sauce preparation, or processed cheese. In addition, availability of residual galactose may result in production of CO₂ by heterofermentative starters and, consequently, in textural defects such as the development of slits and fractures in cheeses. Therefore, the availability of starter strains with improved galactose utilization capacity is desirable to develop higher-quality dairy products. Additionally, strains with increased galactose metabolism could provide galactose-free foods for individuals and, in particular, children suffering from the rare disease galactosemia (36). To this end, a comprehensive understanding of galactose catabolism is essential.

 Galactose metabolism in L. lactis was thoroughly studied in the past and has been and still is the subject of some controversy. Indeed, conflicting results regarding the type of PTS involved in galactose uptake have been published. Some authors advocated that galactose is exclusively transported via the plasmid-encoded PTS^Lac, whereas others proposed transport via a galactose-specific PTS (PTS^Gal) to the extreme of questioning the contribution of the PTS^Lac (17, 20, 50, 59). However, a gene encoding PTS^Gal has never been identified in L. lactis. Independently of the nature of the PTS, it is generally accepted that the resulting Gal6P is metabolized via the Tag6P pathway (lac operon) (Fig. ​(Fig.1).1). On the other hand, galactose translocated via the highly specific galactose permease (GalP) is metabolized via the Leloir pathway to α-glucose 1-phosphate (α-G1P) through the sequential action of galactose mutarotase (GalM), galactokinase (GalK), and galactose 1-phosphate uridylyltransferase (GalT)/UDP-galactose-4-epimerase (GalE) (gal operon). Entry in glycolysis is preceded by the α-phosphoglucomutase (α-PGM)-catalyzed isomerization of α-G1P to G6P. The use of the Leloir and/or the Tag6P pathway for galactose utilization is currently viewed as being strain dependent (9, 16, 25, 32, 33, 58), but the relative efficacy in the degradation of the sugar has not been established.

 The ultimate aim of this study was to engineer L. lactis for improved galactose-fermenting capacity as a means to minimize the galactose content in dairy products. To gain insight into galactose catabolism via the Leloir (gal genes) and the Tag6P (lac genes) pathways, a series of L. 

lactis subsp. cremoris NZ9000 isogenic gal and lac mutants were constructed. Carbon 13 labeling experiments coupled with nuclear magnetic resonance (NMR) spectroscopy were used to investigate galactose metabolism in the gal and lac strains. The data obtained revealed a novel route for galactose dissimilation and provided clues to further enhance galactose utilization.

RESULTS

L. lactis NZ9000 can import galactose via more than one transport system.

L. lactis can use the Leloir pathway, the Tag6P pathway, or both pathways for galactose metabolism in a strain-dependent manner (58). Presumably, L. lactis subsp. cremoris NZ9000 (MG1363pepN::nisRK) internalizes galactose by a secondary carrier symporter (GalP) and further metabolizes the sugar exclusively via the Leloir pathway (25), as this strain lacks the plasmid-linked genes encoding the Tag6P pathway. To assess the potential of the Tag6P route for galactose catabolism, a strategy was devised that consisted of introduction of plasmid pMG820 (41) with genes lacABCDFEG, encoding the lactose PTS (lacFE), the Tag6P pathway enzymes (lacABCD), and a β-phosphogalactosidase (lacG) (64), in mutants in which galactose utilization via the Leloir pathway was prevented. Grossiord et al. (25) previously reported blockage of the Leloir pathway by inactivation of the galactose permease gene. In our study, galP was deleted in strain NZ9000 using a double-crossover recombination method. The extent of the deletion is shown in Fig. ​Fig.22 A. Unexpectedly, L. lactis NZ9000ΔgalP was still able to grow in a medium with galactose as the sole carbon source (Fig. ​(Fig.2B);2B); growth was biphasic and characterized by an initial growth rate that was 2.3-fold lower than a second growth rate, which was similar to that of parent strain NZ9000 (0.38 ± 0.01 h⁻¹). To exclude the possibility of residual GalP activity due to partial deletion only (Fig. ​(Fig.2A),2A), a new out-of-frame deletion was made in which only the first four amino acids of the original protein were left. The behavior of the resulting strain was in all aspects similar to that of our original galP-deletion strain. Subsequently, a mutant strain of L. lactis NZ9000 was made in which, apart from galP, the downstream genes of the operon, galM (galactose mutarotase) and galK (galactose kinase), were also deleted (Fig. ​(Fig.2A).2A). Deletion of galPMK resulted in total loss of the capacity to grow in a medium with galactose as the sole source of carbon (Fig. ​(Fig.2B).2B). These data imply that L. lactis NZ9000 has an additional transport system with specificity for galactose.

L. lactis NZ9000 can catabolize galactose via the Tag6P pathway.

Introduction of pMG820 in L. lactis NZ9000ΔgalPMK rendered a strain that could grow in CDM containing lactose (or glucose, both at 1% [wt/vol]) but not when galactose (1% wt/vol) was the sole carbon source (data not shown). However, resting cells of lactose-grown cultures were able to convert [1-¹³C]galactose (20 mM) to a mixture of fermentation end products, including [3-¹³C]lactate, [2-¹³C]acetate, and [2-¹³C]ethanol, as determined by ¹H NMR spectroscopy (Fig. ​(Fig.3).3). To determine which of the genes within the lac operon were essential for galactose metabolism, the following combinations of genes were cloned into pNZ8048 under the control of the nisin promoter: lacABCD, lacFE, lacABCDFE, and lacABCDFEG. The various constructs were introduced into L. lactis NZ9000ΔgalPMK. Expression of the lac genes in the different constructs was confirmed by SDS-PAGE of cell extracts obtained from nisin-induced (1 μg liter⁻¹) glucose-grown cultures (data not shown). Also, strain NZ9000ΔgalPMK(pLacABCDFEG) was able to grow on lactose (1%, wt/vol)-CDM when the inducer nisin (1 μg liter⁻¹) was added at time 0 h (inoculation). Strain NZ9000ΔgalPMK(pLacABCDFE) showed moderate growth under the same conditions (Table ​(Table3),3), thus showing functional expression of the lac genes. Like NZ9000ΔgalPMK(pMG820), none of the resulting strains was able to grow in CDM with galactose (1%, wt/vol) as the carbon source, even though nisin was added at time 0 h. To determine the galactose-fermenting capacity of NZ9000ΔgalPMK and derivatives harboring the lac constructs, resting cell suspensions were incubated with [1-¹³C]galactose (20 mM), and the end products in the supernatants were examined by ¹H NMR (Fig. ​(Fig.3).3). Strains NZ9000ΔgalPMK(pLacABCD) and NZ9000ΔgalPMK(pLacFE) and the negative control, NZ9000ΔgalPMK, were unable to metabolize galactose, as indicated by the absence of labeled end products in the supernatants. Lactate labeled on carbon 3 was detected in the supernatants of NZ9000ΔgalPMK(pLacABCDFE) and NZ9000ΔgalPMK(pLacABCDFEG), showing that, under the conditions tested (glucose-grown cells), both the Tag6P enzymes (lacABCD) and PTS^Lac (lacFE) are required for galactose consumption in L. lactis NZ9000ΔgalPMK.

 .....

  Future approaches, combining increased expression of catabolic genes, namely, galactose permease and α-PGM, with engineering of the catabolite control network could create L. lactis strains preferring galactose over glucose and lactose, a desirable trait considering that the concentration of lactose in milk fermentations is normally higher than that of galactose (3). Thus, galactose scavengers would be ideal starters in the manufacture of galactose-free dairy products.

....

 3. Alm, A. 1982. Effect of fermentation on lactose, glucose, and galactose content in milk and suitability of fermented milk products for lactose intolerant individuals. J. Dairy Sci. 65:346-352. [PubMed]

NUDT14 ( 14q32.35) Elementaarit solusiivoojaentsyymit Nudixhydrolaasit

Tämä  hiiren ugp-geenin -ortologi ihmisellä UGPP   ja se kuuluu NUDIX hydrolaaseihin, joita on monta ja tämä on  NUDT14.  (Sen toiminta-aluetta on kartoitettu mm. allaolevassa  PubMed artikkelissa) .
Nudisx- hydrolaasit eliminoivat potentiellisti toksisia nukleotidimetaboliitteja solusta ja säätelevät  monien erilisten nukleotidisubstraattien, kofaktoreitten ja signaalimolekyylien   pitoisuuksia ja saatavuutta. Tämä entsyymi sisältää Nudix- hydrolaasi-domeenin ja on UDPG-pyrofosfataasi, joka hydrolysoi UDPG:n  tuottaen glukoosi-1-fosfaattia ja UMP:tä. Alternatiivisesti pleissautunueet transkriptivariantit koodaavat tämän geenin  eri isoformeja. Geeniä ilmenee rasvassa, munuaisessa ja 25 muussa kudoksessa.

• https://www.ncbi.nlm
• .nih.gov/gene/256281

• Also known as UGPP; UGPPase

• Summary

• The protein encoded by this gene is a member of the Nudix hydrolase family. Nudix hydrolases eliminate potentially toxic nucleotide metabolites from the cell and regulate the concentrations and availability of many different nucleotide substrates, cofactors, and signaling molecules. This enzyme contains a Nudix hydrolase domain and is a UDPG pyrophosphatase that hydrolyzes UDPG to produce glucose 1-phosphate and UMP. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

• Expression

Ubiquitous expression in fat (RPKM 8.0), kidney (RPKM 7.1) and 25 other tissues See more

Structure, isoform 1:  (222 aminoacids) ,https://www.ncbi.nlm.nih.gov/protein/NP_803877.2
 Isoform 2:   (149 aminoacids) https://www.ncbi.nlm.nih.gov/protein/NP_001305309.1

• Conserved Domains (1) summary

cl00447
Location:39 → 145

Nudix hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ for their activity. Members of this family are recognized by a highly conserved 23-residue nudix motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of nudix hydrolase include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the nudix hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and "house-cleaning" enzymes. Substrate specificity is used to define child families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.

 

Related articles in PubMed

1. Cloning, expression and characterization of a mammalian Nudix hydrolase-like enzyme that cleaves the pyrophosphate bond of UDP-glucose. Yagi T, et al. Biochem J, 2003 Mar 1. PMID 12429023, Free PMC Article
2. Human cytomegalovirus RL13 protein interacts with host NUDT14 protein affecting viral DNA replication. Wang G, et al. Mol Med Rep, 2016 Mar. PMID 26781650
3. Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis. Yuryev A, et al. Genomics, 2003 Feb. PMID 12620389
4. The DNA sequence and analysis of human chromosome 14. Heilig R, et al. Nature, 2003 Feb 6. PMID 12508121
5. Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. Lee OH, et al. Mol Cell Proteomics, 2011 Feb. PMID 21044950, Free PMC Article

See all (11) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

Preferred Names

uridine diphosphate glucose pyrophosphatase

Names

UDP-sugar diphosphatase

UDPG pyrophosphatase

nudix (nucleoside diphosphate linked moiety X)-type motif 14

NP_001305309.1

• EC 3.6.1.45

NP_803877.2

• EC 3.6.1.45

 

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. the interaction between the RL13 protein and NUDT14 protein may be involved in human cytomegalovirus DNA replication.

Submit: New GeneRIF Correction

Huomaa tässä alla olevassa artikkelissa: 

tiivistelmä. Abstract

UDP-glukoosipyrofosfataasi on tässä työssä luonnehdittu possun munuaisesta. Tämä entsyymi hydrolysoi UDPG- rakennetta, UDP-glukoosia, joka on monen glykosylaatioreaktion edeltäjämolekyyli eläimillä ja  tuotteina on glukoosi-1-fosfaattia (Glc1P)  ja UMP:tä Sekvenssianalyyseissä tämä UGPPaasi- entsyymi  osoittautui   nukleotidi-sokerihydrolaasien tavoin olevan  jäsen yleisesti  esiintyvissä nukleotidipyrofosfataasien ryhmässä, Nudix-hydrolaasin joukossa. Täydellinen  cDNA eristettiin  UGPPaasia koodaavasta geenistä, jolle annettiin nimi UGPP.  cDNA  eristettiin kilpirauhasen cDNA-kirjastosta ja ilmennettiin E-Colissa.  Tulossolut akkumuloivat proteiinia, jolla osoittautui  olevan kineettisten ominaisuuksien identtisyydet  possun UGPPaasi- entsyymin kanssa.

• A distinct UDP-glucose (UDPG) pyrophosphatase (UGPPase, EC 3.6.1.45) has been characterized using pig kidney ( Sus scrofa ). This enzyme hydrolyses UDPG, the precursor molecule of numerous glycosylation reactions in animals, to produce glucose 1-phosphate (G1P) and UMP. Sequence analyses of the purified enzyme revealed that, similar to the case of a nucleotide-sugar hydrolase controlling the intracellular levels of ADP-glucose linked to glycogen biosynthesis in Escherichia coli [Moreno-Bruna, Baroja-Fernández, Muñoz, Bastarrica-Berasategui, Zandueta-Criado, Rodri;guez-López, Lasa, Akazawa and Pozueta-Romero (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 8128-8132], UGPPase appears to be a member of the ubiquitously distributed group of nucleotide pyrophosphatases designated Nudix hydrolases. A complete cDNA of the UGPPase-encoding gene, designated UGPP, was isolated from a human thyroid cDNA library and expressed in E. coli. The resulting cells accumulated a protein that showed kinetic properties identical to those of pig UGPPase.Full Text The Full Text of this article is available as a PDF (383K).

 https://www.uniprot.org/uniprot/O95848

(Saattaa olla että tämä entsyymi  ei avusta galaktoosiaineenvaihdunnan puolella ihmisellä. ehkä jokin toinen hydrolaasi  olisi  sillä puolella.  Vasta kun galaktoosista jo on tullut  UDP-Glc, tämä entsyymi voi vaikuttaa.   

 

UGP geeni UGP entsyymit: UDP-gluPP ja UDP-galPP

Lähde
Artikkeli kertoo hiirillä tehdystä geenitutkimuksesta. Ihmisen ortologi tälle geenille on  NUDT14.
 

UDP-glu -pyrofosfataasi ( UGP -geenin koodaama entsyymi)  tuottaa UDP-glukoosia, joka on kriittinen glykogeenin synteesille ja se myöskin katalysoi reaktiota UTP:n ja galaktoosi-1-fosfaatin kesken   tuottaen  UDP-galaktoosiakin.

Tämä jälkimmäinen funktio  samalla UGP -entyymille jota voi tässä kohtaa kutsua UDP_gal- pyrofosforylaasiksi (UDPgalPP) nimellä,  viittaisi siihen, että galaktoosiaineenvaihdunnassa  on alternatiivinen askel päästä pois  toksisesta  galaktoosimuodosta ( aktivoituun UDP-gal muotoon) , jos  on puute GALT-entsyymistä. 

Tutkijat selvittivät   GAL puutemallin  ja galaktoosipitoisen dieetin avulla  UGP- entsyymin  erilaisia aktiivisuuksia koe-eläimessä:  UDP-gluPP ja UDP-galPP aktiivisuudet. ( GALT entsyymiin oli vaikutettu kriittiseen kohtaan  homozygootti deleetio). UGP- entsyymi osoitti  merkitsevästi suurempaa aktiivisututa glukoosi-1- fosfaattia kohtaan  verrattuna  galaktoosi-I-fosfaattiin substraattina.  GALT vajeisilla  koe-eläimillä oli kontrolleihin verrattuna alempi UDP-galPP-aktiivisuus.  Ero kuitenkin katosi,   kun suoritettiin  tähteenä olleen UDP-glukoosin ( jäänne- GALT vaikutuksen ) poisto, sillä GALT omaa 100 kertaa suuremman aktiviteetin gal-1-fosfaattia kohtaan  kuin  UDP-galPP- entsyymi maksahomogenaatissa.  Edeltänyt altistus tavalliselle rehulle, runsasgalaktoosiselle rehulle  ja runsasglukoosiselle rehulle ei tehnyt  muutoksia UDP-gluPP tai UDP-galPP aktiivisuuksiin. UGP mRNA pitoisuudet määritettiin perustilasta normaalien ja  GALT -vajeisten   eläinten kudoksista. UGP-ilmentymä oli korkeimmillaan maksassa  eikä siihen vaikuttanut genotyyppi tai altistus runsasgalaktoosiselle rehulle. GALT - vajeisilla eläimillä saattaa UDP-galPP-aktiivisuus vastata selittämättömästä kyvystä oksidoida galaktoosia, mutta tämä  kyky on riittämätön muuntamaan galaktoosimetaboliittien akkumuloitumista .

• Mol Genet Metab. 2005 May;85(1):21-7. Epub 2005 Feb 23. UDP-galactose pyrophosphorylase in mice with galactose-1-phosphate uridyltransferase deficiency.

• Leslie N¹, Yager C, Reynolds R, Segal S.AbstractUDP-glucose pyrophosphorylase (E.C. 2.7.7.9), encoded by ugp, provides UDP-glucose which is critical to the synthesis of glycogen, and also catalyzes the reaction between UTP and galactose-1-phosphate, yielding UDP-galactose. This activity of UDP-gal pyrophosphorylase (UDP-galPP) suggests a role in an alternate pathway for galactose metabolism in patients with deficiency of galactose-1-phosphate uridyltransferase (GALT).

•  We examined the effects of GALT deficiency and dietary galactose on UDP-glucose pyrophosphorylase (UDP-gluPP) and UDP-galactose pyrophosphorylase activity and ugp expression in liver of mice with homozygous deletion of the critical regions of galt. Activity with glucose-1-phosphate as substrate was significantly higher than that with galactose-1-phosphate. In liver from mice with GALT deficiency (G/G), UDP-galPP activity appeared to be lower than that measured in liver from control (N/N) animals. This difference disappeared when the N/N tissue homogenate was dialyzed to remove residual UDP-glucose, confirming that careful elimination of residual GALT activity is necessary, since GALT has 1000-fold greater activity toward galactose-1-phosphate than that of UDP-galPP in liver homogenates. 

• Prior exposure to conventional mouse chow, high galactose chow, and high glucose chow did not alter UDP-glu PP or UDP-galPP activity. Steady state UGP mRNA levels were determined in tissues from normal and G/G animals. UGP expression was highest in liver, and did not differ by genotype or exposure to high galactose chow. UDP-galPP activity may account for unexplained ability to oxidize galactose in animals with no GALT activity, but is insufficient to alter accumulation of galactose metabolites. PMID 15862277
• DOI: 10.1016/j.ymgme.2005.01.004

GALT (9p13.3,Galaktoosi-1- fosfaatti-uridyylitransferaasi

https://www.ncbi.nlm.nih.gov/gene/2592
 GALT entsyymi katalysoi  toista askelta  Leloirin tiessä ( galaktoosiaineenvaihdunnan päätiessä) , jossa  tapahtuu sekä  UDP-glukoosin että  Gal-1-fosfaatin  muuttumiset UDP-galaktoosiksi ja Glc-1-fosfaatiksi ( yksisuuntaisesti) . Jos  Galaktoosi-1- fosfaatti ei pääse muuntumaan tässä kohtaa  glukoosin puolelle tai  aktivoitumaan  UDP-galaktoosiksi ( ja  myöhemmin UDP-glukoosiksi) , seuraa  galaktoosin pakkautumista siten,  että  ihmisellä havaitaan  klassista galaktosemiaa . Vastasyntyneillä  voi olla hengenvaarallista, jos dieetin laktoosi ei imeydy.  (Laktoosia  ihmiskeho  tarvitsee  rintamaidon tuotantoon  ja vstasyntyneen aivon ja keskushermoston kehittymiseen).   Galaktosemian  patofysiologiaa ei ole selkeästi määritelty. GALT. geenistä  on  kaksi transkriptivarianttia  jotka koodaavat eri isoformeja. Geeniä ilmenee pohjukaissuolessa, maksassa ja 25 muussa kudoksessa.
PubMed -geenireferaateissa mainitaan seuraavaa:
1992 laktosemian geneettinen tausta selvitettiin. Samana vuonna  havaittiin GALT entsyymissä mutaatioita  (missense mutations). Ihmisen Galaktoosi-1-fosfaatti-uridyltransferaasin geeni GALT  oli myös selvitetty.  Hereditäärisen dystonian  yleiskatsaus  1993.   Vuonna 1993 erotettiin klassinen galaktosemia ja  kliininen variantti.  Duarten variantti galaktosemiasta.
Vuonna 2007 oli olemassa GALT  mutaatioista  perustavat tietueet .
 Vuonna 2017 havaittiin  Equadorista uusi GALT- mutaatio, joka johtaa galaktosemiaan. Myös Kreikassa todettiin kaksi uutta mutaatiota.  2018 on julkaistu tietoa kroatialasväestössä  esiintyvästä  klassisesta  galaktosemiasta.
Tähän mennessä on julkaistu tietoa yli 300  GALT mutaatiosta, jotka assosioituvat tautiin. 
Näissä viitteissä ei ole tästä geenistä  näkyvää yhteyttä  diabeettisuuteen. 

• Summary: Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
•  Expression  Ubiquitous expression in duodenum (RPKM 23.8), liver (RPKM 21.4) and 25 other tissues See more

• Preferred Names

  galactose-1-phosphate uridylyltransferase

  Names

  UDP-glucose--hexose-1-phosphate uridylyltransferase

  gal-1-P uridylyltransferase

  galactose-1-phosphate uridyl transferase

  NP_000146.2

  • EC 2.7.7.12

  NP_001245261.1

  • EC 2.7.7.12

   
•  https://www.ncbi.nlm.nih.gov/pubmed/27005423
• Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 Å resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease-associated mutants.
• 
  

ORIGIN      
        1 msrsgtdpqq rqqaseadaa aatfrandhq hirynplqde wvlvsahrmk rpwqgqvepq
       61 llktvprhdp lnplcpgair angevnpqyd stflfdndfp alqpdapspg psdhplfqak
      121 sargvckvmc fhpwsdvtlp lmsvpeirav vdawasvtee lgaqypwvqi fenkgammgc
      181 snphphcqvw assflpdiaq reersqqayk sqhgepllme ysrqellrke rlvltsehwl
      241 vlvpfwatwp yqtlllprrh vrrlpeltpa erddlasimk klltkydnlf etsfpysmgw
      301 hgaptgseag anwnhwqlha hyyppllrsa tvrkfmvgye mlaqaqrdlt peqaaerlra
      361 lpevhyhlgq kdretatia
//

 

Related articles in PubMed

1. Molecular basis and clinical presentation of classic galactosemia in a Croatian population. Ramadža DP, et al. J Pediatr Endocrinol Metab, 2018 Jan 26. PMID 29252199
2. Mutational analysis of GALT gene in Greek patients with galactosaemia: identification of two novel mutations and clinical evaluation. Schulpis KH, et al. Scand J Clin Lab Invest, 2017 Oct. PMID 28644047
3. A novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family. De Lucca M, et al. Clin Chim Acta, 2017 Jul. PMID 28450132
4. Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia. Liu Y, et al. Clin Chim Acta, 2015 Jun 15. PMID 25920691, Free PMC Article
5. Clinical and molecular spectra in galactosemic patients from neonatal screening in northeastern Italy: structural and functional characterization of new variations in the galactose-1-phosphate uridyltransferase (GALT) gene. Viggiano E, et al. Gene, 2015 Apr 1. PMID 25592817

See all (115) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. GALT mutation is associated with galactosemia.
2. The mutational spectrum of the GALT gene in Greek galactosemia patients is presented for the first time.
3. novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family
4. 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain
5. we present the 1.9 A resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer
6. A novel noncoding homozygous GALT variant associated with asymptomatic galactosemia has been described in an infant of consanguineous heterozygous parents.
7. Mutation activates a cryptic donor splice site, inducing an aberrant splicing of the GALT pre-mRNA, which in turn leads to a frameshift with inclusion of a premature stop codon.
8. GALT activity in red blood cells of patients with galactosaemia
9. Novel missense mutations identified in Italian galactosemic patients.
10. In Korean population, novel GALT mutations were identified in the galactosemia patients different from those of other populations.

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Diabeteksen vaikuttama sokeriaineenvaihdunnan tuoteprofiili lasiaisessa

Galaktoosin osuus verensokerissa   kaiketi ei ole niin merkittävä kuin fruktoosin ja glukoosin, joten siihen ei niin kiinnitetä huomiota,  mutta  sen sijaan se merkitsee diabeteksen  pitkäaikaisvaurioissa, joten se on syytä ottaa huomioon. Galaktoosin aineenvaihdunta on  entsyymikartaltaan puutteellista, joten  siitä voi  seurata aineenvaihdunnan huonontuessa   akkumulaatiota eri sijaintikohdissa kompromittoiduisaa aitioissa.

Yksi aitio on silmän lasiainen, toinen aitio on  likvor ja ehkä koko  BBB:n takainen  aivo.
Galaktitolin muodostus  silmän sisällä johtaa lopulta proteiiniaddukteihin ja samennuksiin lasiaisessa. 


Lasiaisen sokeritilannetta on tutkittu normaaliaineenvaihdunnan omaavilta ja diabeettisen aineenvaihdunnan omaavilta ja vertailtu   lasiaisessa esiintyviä sokerimolekyylimuotoja.
Ei diabeettisissa  muodostui enemmän tuotteena galaktitolia, jolla ilmisesti oli vielä pääsy pois silmästä ja kehosta eritysteitse.
Diabeettisillä  (proliferatiivisessa diabeettisessa retinopatiassa)  jäi  kertymään laktaattia ja  glukoosia  enemmän kuin  ei-diabeettisilla yksilöillä.  Galaktitoli metaboliitin   ja  askorbiinihapon määrissä oli myös eroja. Ne olivat alemmat  retinopatiassa.

•  https://iovs.arvojournals.org/article.aspx?articleid=2126261

• Results.: Lactate was the most abundant metabolite, and it was present at higher levels in samples from PDR patients than from nondiabetic patients (P = 0.02). Glucose was significantly higher in samples from PDR patients than nondiabetic patients (P = 0.03). After removing the lactate peak at 1.35 ppm and with the use of PLS-DA, a model was obtained that was able to correctly classify 19 of 22 patients with PDR and 18 of 22 controls, resulting in a sensitivity of 86% and a specificity of 81%. The main metabolites involved in this specific pattern recognition were galactitol and ascorbic acid (AA); levels of both were significantly lower in PDR patients.

• Conclusions.: ¹H-NMR–based metabonomic analysis of vitreous fluid permits the obtainment of a metabolic signature of PDR. Apart from the higher abundance of lactate and glucose, significant deficits of galactitol and AA are the main metabolic fingerprints of vitreous fluid from PDR patients.

https://www.ncbi.nlm.nih.gov/pubmed/17341153
Retinal vascular changes begin with an initial degeneration of capillary pericytes, which has been linked to the aldose reductase catalyzed formation of galactitol. Because aldose reductase-linked sugar cataract formation is known to be age dependent, with the onset and severity of cataract higher in younger diabetic and galactose-fed animals, retinal capillary changes in the eyes of initially 2- versus 9-month-old beagles fed a diet containing 30% galactose were compared..
https://www.liebertpub.com/doi/10.1089/jop.2006.0069

Entä munuainen ja  galaktitoli?

https://www.ncbi.nlm.nih.gov/pubmed/14741191

Vuodelta 2004 löytyy eläinkoe asiasta: Galaktitolin ja galaktonaatin suuri  akkumuloituminen sydämeen ja tahdonalaiseen lihakseen tapahtuu sellaisilla hiirillä, joilla on vaje Gal-1-P-uridyltransferaasientsyymistä  (GALT).   Sen sijaan galaktitolin kertymä  maksaan, aivoon ja munuaiseen on vähäisempää.  Koe-eläimien galaktoosdieetti oli hurja , 40%. Näin suuri galaktoosirasitus tietysti tulee korostetusti esiin  galaktoosin metaboliassa, koska  se on entsyymivarustuksilta rajoitetumpi kuin vastaava  glukoosisokerin metabolia ( vert. glukoosirasitukseen). Koe-eläinten  sydämen galaktitolipitoisuus  22 umol/g kudosta ja vastaavasti lihaksessa  38.33. umol/g. Nämä pitoisuudet olivat 40-100 kertaa gal-1-P pitoisuuksia suuremmat. Sydän ja lihas pystyivät muodostamaan myös galaktonaattia rasituksen alaisina.Nämä tiedot painottavat  sydämen ja luustolihaksen mahdollista osuutta  galaktoosin  aineenvaihdunnan täydentäjinä, kun GALT aktiivisuus on  heikentynyt, sillä lihasrasitus  näkyy  eritystien tehostumisessa:  metaboliitteja galaktitolia ja  galaktonaattia pääsee erittymään munuaisten kautta pois kehosta.  Tätä  sydän ja luustolihastietä galaktoosiaineenvaihdunnan välituotteita voi oksidoitua hiilidioksidiksi asti.

• Mol Genet Metab. 2004 Feb;81(2):105-11.Galactitol and galactonate accumulation in heart and skeletal muscle of mice with deficiency of galactose-1-phosphate uridyltransferase.

• Yager C¹, Ning C, Reynolds R, Leslie N, Segal S. Abstract

• Under conditions of dietary galactose loading, mice deficient in galactose-1-phosphate uridyltransferase (GALT) accumulate large amounts of galactitol and galactonate in heart and skeletal muscle. In contrast to liver, brain, and kidney, which form little galactitol when GALT-deficient animals (G/G) ingest a 40% galactose diet, heart and skeletal muscle galactitol reaches 22.90+/-1.62 (M+/-SE) and 38.88+/-2.62 micromol/g tissue, respectively, levels 40-100 times that of galactose-1-phosphate (Gal-1-P). Sixteen-day-old suckling G/G mice accumulate galactitol in heart and to a lesser extent, in skeletal muscle. Heart and skeletal muscle of G/G mice also form galactonate, with levels comparable to that of liver, which was presumed previously to be the only tissue capable of converting galactose to galactonate under conditions of loading. The data suggest that heart and skeletal muscle play a role in disposition of galactose when GALT activity is impaired, contributing a large share to urinary galactitol and galactonate excretion. The ability of heart and muscle to form galactonate may also contribute to the G/G mouse's ability to slowly oxidize galactose to CO2, since the compound is an intermediate in an alternate route for galactose disposition.

• PMID:
• 14741191

Siis liikunnalla  (sydän ja tahdonalainen lihaksisto)  voi avustaa puuteellista galaktoosiaineenvaihduntaansa. Ihminen on luotu liikkumaan, joten  Luoja aluksi asetti  rahkeet sen mukaan. Vasta viime  vuosituhannen tai  -sadan  aikana ihminen on valinnut olla liikkumatta "jos saa valita".   Mutta galaktoosiaineenvaihdunta ei ole keksinyt uusia  alternatiiveja. Onneksi  aivot, jotka galaktoosia eniten tarvitsevat   aivojen kasvuvaiheessa lapsuudessa, on kehittänyt tieteellistä tutkimusta asiasta,  joten ihminen voi orientoitua. Tämä oli muuten  hieno löytö, sillä  olen ajatellut että galaktoosiaineenvaihdunta on kuin "umpisuolen lisäke",  Ikäänkuin umpio, josta  ei johda tietä minnekkään, mutta  joka  tekee jotain tärkeää tai  aiheuttaa paljon haittoja Toisaalta  galaktoosin erikoinen  vajaa metabolia voi olla tapa sen säilymiseen kehon  esentielleissä struktuureissa osana.  Tietysi myös koko luomakunnassa galaktoosilla on osuutensa vahvoissa struktuureissa.