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PubMed1976

Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver.

The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under steady-state conditions, is removed from the blood that flows through the sinusoids by an irreversible process which follows Michaelis-Menten (i.e., saturation) kinetics. The experiments consisted of successive periods with constant infusions of galactose. The model fitted the data to within the experimental uncertainty. The estimated maximal rate (Vmax) ranged from 0.34 to 0.57 mmol-min(-1)-kg(-1) liver, and the Michaelis constant, Km, ranged from 0.12 to 0.30 mmol-liter(-1) plasma water in nine experiments. The ratio between the galactose concentration in hepatocyte water and plasma water was not significantly different from 1.0, indicating that membrane transport is not rate limiting for the elimination of galactose. In experiments with increasing concentrations of galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant. This indicates that the phosphorylation of galactose to galactose 1-phosphate is the rate-determining process.

Animals↗
PubMed2002

Combined biosynthetic pathway for de novo production of UDP-galactose: catalysis with multiple enzymes immobilized on agarose beads.

Regeneration of sugar nucleotides is a critical step in the biosynthetic pathway for the formation of oligosaccharides. To alleviate the difficulties in the production of sugar nucleotides, we have developed a method to produce uridine diphosphate galactose (UDP-galactose). The combined biosynthetic pathway, which involves seven enzymes, is composed of three parts: i) the main pathway to form UDP-galactose from galactose, with the enzymes galactokinase, galactose-1-phosphate uridyltransferase, UDP-glucose pyrophosphorylase, and inorganic pyrophosphatase, ii) the uridine triphosphate supply pathway catalyzed by uridine monophosphate (UMP) kinase and nucleotide diphosphate kinase, and iii) the adenosine triphosphate (ATP) regeneration pathway catalyzed by polyphosphate kinase with polyphosphate added as an energy resource. All of the enzymes were expressed individually and immobilized through their hexahistidine tags onto nickel agarose beads ("super beads"). The reaction requires a stoichiometric amount of UMP and galactose, and catalytic amounts of ATP and glucose 1-phosphate, all inexpensive starting materials. After continuous circulation of the reaction mixture through the super-bead column for 48 h, 50 % of the UMP was converted into UDP-galactose. The results show that de novo production of UDP-galactose on the super-bead column is more efficient than in solution because of the stability of the immobilized enzymes.

Catalysis↗
PubMed2002

Surface immobilization of galactose onto aliphatic biodegradable polymers for hepatocyte culture.

A novel surface modification method of biodegradable polymers was investigated for inducing the attachment of specific cells onto the polymer surface via ligand-receptor interactions. Galactose, a targeting ligand specific to asialoglycoprotein receptors present on cell membrane of hepatocytes, was introduced on the surface of poly(D,L-lactic-co-glycolic acid) (PLGA) films. A terminal end group of carboxylic acid in PLGA was activated by dicyclohexylcarbodiimide and N-hydroxysuccinimide for the direct conjugation of lactose by reductive amination reaction. Di-block copolymers of PLGA-b-poly(ethylene glycol) (PEG) having a free terminal amine group were also synthesized and used for the conjugation of galactose for the introduction of a PEG spacer between PLGA and galactose. The presence of galactose moieties on the blend film surface was characterized by measuring water contact angle and X-ray photon spectroscopy, and the amount of galactose was indirectly determined by a specific lectin-binding assay. With increasing the galactose concentration on the blend film surface, the initial attachment as well as the cell viability of hepatocyates concomitantly increased. The introduction of PEG spacer reduced the cell attachment and viability. Albumin secretion rate from hepatocytes was enhanced for galactose modified surfaces, whereas it was reduced for the surfaces not having galactose moieties.

Animals↗
PubMed2005

Gene-expression profiles for five key glycosylation genes for galactose-fed CHO cells expressing recombinant IL-4/13 cytokine trap.

Recombinant protein glycosylation profiles have been shown to affect the in-vivo half-life, and therefore the efficacy and economics, for many therapeutics. While much research has been conducted correlating the effects of various stimuli on recombinant protein glycosylation characteristics, relatively little work has examined glycosylation-related gene-expression profiles. In this study, the effects of galactose feeding on the gene-expression profiles for five key glycosylation-related genes were determined for Chinese hamster ovary cells producing a recombinant IL-4/13 cytokine trap fusion. The genes investigated were sialidase, a putative alpha2,3-sialyltransferase, CMP-sialic acid transporter, beta1,4-galactosyltransferase, and UDP-galactosyltransferase. Additionally, the sialic acid content (sialylation) of the recombinant protein was examined. The peak sialic acid content of the IL-4/13 cytokine trap fusion protein was observed to be similar for the control and galactose-fed cultures. The gene-expression profiles for four of the glycosylation genes were observed to be sensitive to the glucose concentration and not significantly different for the control and galactose-fed cultures prior to glucose depletion. However, the sialidase gene-expression profiles were different for the control and galactose-fed cultures. The sialidase gene-expression profile increased significantly for the galactose-fed cultures prior to glucose depletion, whereas for the control cultures, the sialidase gene-expression profiles did not increase until the late stationary phase. The intracellular sialidase enzyme activity decreased exponentially with time for the control cultures; however, for the galactose-fed cultures, the intracellular sialidase enzyme activity decreased initially and then remained relatively high compared to the control cultures. These results indicate that the galactose feeding may increase the potential for desialylation, which offsets any improvements in the sialylation rate due to increased substrate levels. Thus, galactose feeding is an unnecessary expense for the production of the IL-4/13 cytokine trap fusion protein in a batch process.

Animals↗
PubMed1992

Analysis of glucose repression in Saccharomyces cerevisiae by pulsing glucose to a galactose-limited continuous culture.

In this study, glucose repression in Saccharomyces cerevisiae was analysed under defined physiological conditions, at both the molecular and physiological levels, by pulsing glucose to a galactose-limited continuous culture. During this pulse of glucose, the galactose feed was kept constant. Directly after the glucose pulse, carbon dioxide production increased while oxygen consumption remained constant, demonstrating that the surplus of glucose had been consumed by means of fermentation. The direct accumulation of galactose in the medium after the glucose pulse indicated that the consumption of galactose had been stopped instantaneously. Galactose uptake experiments revealed that the galactose transporter was still present but apparently was incapable of galactose uptake, which could be due to inhibition of the galactose transporter by glucose. The total concentration of cAMP increased from 5 nmol g-1 at t = 0 to 25 nmol g-1 at t = 1.5 min. After 2 min the concentration of cAMP gradually decreased again to the normal level. Within 2 min after the addition of glucose, the transcription of the GAL genes and SUC2 was inhibited. In addition, the transcription of the HXK1 gene, encoding hexokinase isoenzyme 1, was also inhibited, which demonstrates that the HXK1 gene is regulated at the transcriptional level comparable with invertase.

Adenosine Triphosphate↗
PubMed1992

Transient elevation of aldose reductase mRNA in lens of rats developing galactose cataracts.

Aldose reductase (AR), a major enzyme in the polyol pathway, is thought to be responsible for accumulation of polyols in lenses exposed to high doses of galactose or glucose, and it may be linked to some of the complications found in diabetes. In this report we examined the level of expression of AR mRNA in lens epithelia undergoing development of galactose cataracts in vivo. The AR mRNA was quantitated by Northern blot hybridization with a [35S]-RNA transcript from a previously described AR cDNA clone. This was done on normal lens epithelia and on epithelia from lens of rats fed a diet of Purina Chow containing 50% galactose for periods of from 6 hr to 20 days. We found AR mRNA to elevate to about 5-fold the control levels by 12-24 hr on galactose, then decrease to the control levels by day 4. The increase in AR mRNA appears to be transitory. The high abundance in AR mRNA by 24 hr on galactose was confirmed by in situ hybridization. At later periods, from 8 to 20 days on galactose, a slow increase in AR mRNA took effect, as we have previously reported. Changes in the levels of galactose and dulcitol between 0 and 96 hr were also quantitated by gas chromatography, showing that there was a significant increase in both galactose and dulcitol occurring throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1997

Schwann cell changes induced as early as one week after galactose intoxication.

In galactose neuropathy, aldose reductase inhibitor (ARI)-preventable Schwann cell injury has been reported in studies in which galactose feeding continued over a period of months. Given the link between these morphologic changes and polyol pathway flux, polyol accumulation after just days of galactose feeding points to the possibility that structural changes occur much earlier than previously reported. The aim of this study was to examine rat sciatic nerve after 7 days of galactose feeding for evidence of myelinated fiber injury and establish whether it is related to polyol accumulation. Compared to control or ARI-treated galactose-fed rats, nerves from untreated galactose-fed rats had increased water (P < 0.05) ad dulcitol (P < 0.008) content and decreased amounts of myo-inositol (P < 0.01). Electron microscopy revealed reactive Schwann cell changes in myelinated fibers characterized by increased cytoplasmic volume, and the occurrence of lipid droplets pi granules of Reich and enlarged mitochondria. Dystrophic accumulation of intermediate filaments was also observed in the inner glial loop. Degenerative changes included periaxonal swelling, enlarged mitochondria without recognizable cristae, lysis of Schwann cell cytoplasm and demyelination. Reactive (P < 0.05) and degenerative (P < 0.01) changes as well as the number of redundant basal lamina profiles (P < 0.05) were significantly more frequent in untreated galactose-fed rats compared to controls. ARI treatment attenuated these changes. Consistent with the initial stages of onion-bulb formation, profiles with imbricate Schwann cells were also seen only in untreated galactose-fed rats. The findings suggest that short-term increases in polyol pathway activity can have deleterious effects Schwann cells of myelinated fibers.

Administration, Oral↗
PubMed2006

Two familial cases of high blood galactose of unknown aetiology.

We report two male siblings presenting as newborns with increased blood galactose, urinary excretion of galactitol, and normal galactose 1-phosphate on a breast milk diet. A lactose-free diet led to normalization of all metabolites, while reintroduction of galactose in the diet resulted in an accumulation of metabolites. Potential causes of galactosaemia include: (1) activities of three enzymes of galactose metabolism: galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT), and uridine diphosphate galactose 4'-epimerase (GALE), (2) portosystemic shunting, (3) Fanconi-Bickel syndrome, (4) tyrosinaemia. Each was excluded with appropriate tests. These two familial cases may represent a novel autosomal or X-linked recessive disorder of galactose metabolism, possibly due to a novel defect in the transport of galactose across the plasma membrane.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1986

Characteristics of D-galactose transport systems by luminal membrane vesicles from rabbit kidney.

The characteristics of renal transport of D-galactose by luminal membrane vesicles from either whole cortex, pars recta or pars convoluta of rabbit proximal tubule were investigated by a spectrophotometric method using a potential-sensitive carbocyanine dye. Uptake of D-galactose by luminal membrane vesicles prepared from whole cortex was carried out by an Na+-dependent and electrogenic process. Eadie-Hofstee analysis of saturation-kinetic data suggested the presence of multiple transport systems in vesicles from whole cortex for the uptake of D-galactose. Tubular localization of the transport systems was studied by the use of vesicles derived from pars recta and pars convoluta. In pars recta, Na+-dependent transport of D-galactose and D-glucose occurred by means of a high-affinity system (half-saturation: D-galactose, 0.15 +/- 0.02 mM; D-glucose, 0.13 +/- 0.02 mM). These results indicated that the "carrier' responsible for the uptake of these hexoses does not discriminate between the steric position of the C-4 hydroxyl group of these two isomers. This is further confirmed by competition experiments, which showed that D-galactose and D-glucose are taken up by the same and equal affinity transport system by these vesicle preparations. Uptake of D-galactose and D-glucose by luminal membrane vesicles isolated from pars convoluta was mediated by a low-affinity common transport system (half-saturation: D-galactose, 15 +/- 2 mM; D-glucose, 2.5 +/- 0.5 mM). These findings strongly suggested that the "carrier' involved in the transport of monosaccharides in vesicles from pars convoluta is specific for the steric position of the C-4 hydroxyl group of these sugars and presumably interacts only with D-glucose at normal physiological concentration.

Animals↗
PubMed1989

Tumor cell-surface galactose correlates with the degree of colorectal liver metastasis.

The phenotypic heterogeneity of tumor cell-surface galactose expression within a cell population may dictate metastatic potential. The hepatic asialoglycoprotein receptor, whose known function is to bind to terminal galactose residues of desialylated glycoproteins and effete cells, may participate in the arrest and subsequent growth of subpopulations of tumor cells with high galactose expression. To test this hypothesis, murine colon carcinoma cells (CT-26) were sorted, using the galactose-specific lectin, soybean agglutinin (SBA), and fluorescence-activated cell-sorting (FACS) technology, into two subpopulations--one low in surface galactose and one high in surface galactose. After intrasplenic injection of tumor cell subpopulations, liver metastasis was found to be proportional to the degree of tumor cell-surface galactose expression. These data suggest that tumor galactose expression and hepatic recognition may be important components of a specific mechanism of colorectal liver metastasis.

Adenocarcinoma↗
PubMed1986

Edema and increased endoneurial sodium in galactose neuropathy. Reversal with an aldose reductase inhibitor.

Galactose neuropathy was produced in rats by feeding a diet containing 30% D-galactose. After 12 weeks of galactose ingestion, all rats developed bilateral cataracts, polydypsia and polyuria. These galactose-intoxicated animals were divided into two groups that both continued with the galactose diet: animals that were treated with the aldose reductase inhibitor, ICI 128,436, for 4-6 weeks, and a control group of animals that received just excipient. At the end of the study, endoneurial fluid pressures, nerve water contents and endoneurial fluid electrolyte concentrations were determined from sciatic nerves of treated and untreated animals. The extent of neuropathy in each animal was evaluated by light microscopy. Treatment of galactose-intoxicated rats with ICI 128,436 restored to normal levels the elevated endoneurial sodium concentration, increased water content and interstitial fluid pressure characteristic of galactose neuropathy. These results, obtained with an agent that blocks the sorbitol pathway, associate elevated sodium with an osmotic force contributing to edema and increased endoneurial fluid pressure in galactose neuropathy and suggest that endoneurial sodium levels are linked to blood-sugar concentration.

Animals↗
PubMed1978

Galactose and glucose metabolism in the isolated perfused suckling and adult rat liver.

The development of the technique for the perfusion of the immature liver has enabled us to characterize metabolic differences in carbohydrate metabolism in the suckling versus adult rat livers. Livers of fasted suckling and adult rats were perfused with 4 mM galactose or 4 mM glucose. Galactose uptake was the same for both age groups during the first 35 min. The adult liver maintained the initial rate of uptake after this period while the immature liver began to take up galactose more rapidly. By the end of the experimental period, on a weight basis, uptake by the young liver was three times that of the adult. Analysis of the livers at the end of the 90 min perfusion showed hepatic galactose concentrations to be one-half of circulating media levels. Glucose output was observed in each group during perfusion with either galactose or glucose. In the immature liver, galactose perfusion stimulated more glucose output than did the glucose perfusion. In the adult, however, both sugars resulted in the same levels of glucose output. Galactose perfusion resulted in glucose levels in young liver being higher than the media; while in the adult, the level was lower than the media. Galactose perfused livers of the suckling and adult contained significantly more uridine-5'-diphosphogalactose than the glucose perfused livers of each age.

Aging↗
PubMed1990

Galactose clearance and carbohydrate metabolism across the gastrointestinal tract in the newborn lamb.

We prepared 16 newborn lambs with chronically indwelling catheters in the portal vein, mesenteric vein, femoral vein, and femoral artery to study galactose clearance, portal venous blood flow, and carbohydrate metabolism across the gastrointestinal (GI) tract. Galactose clearance was measured by infusing galactose into the femoral vein to achieve a steady-state galactose concentration in the femoral artery. We observed a curvilinear relationship between galactose clearance and the steady-state galactose concentration. The relationship could be modeled as an apparent Michaelis-Menten system: Clearance = Vmax/(Km + [Gal]ssa), where Vmax = 17.0 +/- 2.5 mg/min/kg body weight and Km = 11.0 +/- 0.4 mg/dL. Substrate/oxygen quotients across the viscera drained by the portal vein were measured in the fasted state and during systemic galactose infusion. A net uptake of glucose and galactose by the GI tract was found with quotients of 0.19 +/- 0.07 and 0.05 +/- 0.02, respectively. There was a relatively large net efflux of lactate across the portal circulation, with a quotient of -0.13 +/- 0.03. The indicator-dilution technique was used to estimate portal venous blood flow (PVBF) in the neonatal period with a resting, fasted state value of 92.8 +/- 4.4 mL/min/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Acute and chronic exposure of mouse cerebral microvessel endothelial cells to increased concentrations of glucose and galactose: effect on myo-inositol metabolism, PGE2 synthesis, and Na+/K(+)-ATPase transport activity.

Cultured mouse cerebral microvessel endothelial cells have a large intracellular myo-inositol content and rapidly take up extracellular myo-inositol. Myo-inositol uptake occurs by a high- and low-affinity transport system. Both transport systems appear to be Na(+)-dependent. The high- and low-affinity transport systems have a Km of 11 and 198 mumol/L and a Vmax of 47 and 381 pmol/min/mg protein, respectively. Acute exposure of cultured cells to 30 mmol/L D-glucose or D-galactose causes a decrease in myo-inositol uptake. The acute effect of glucose and galactose on myo-inositol uptake is sensitive to the extracellular myo-inositol concentration. The acute effect of glucose is apparently due to a competitive inhibition of high-affinity myo-inositol transport and has a Ki of 21 mmol/L. L-Glucose is more effective than D-glucose in decreasing myo-inositol uptake. In contrast, 2-deoxyglucose or 3-0-methylglucose does not acutely inhibit myo-inositol uptake. This suggests that the hydroxyl groups on carbons 2 and 3 of glucose are necessary for inhibitory activity. Chronic exposure of cells to media containing 136.4 mumol/L myo-inositol and 30 mmol/L glucose has no effect on myo-inositol accumulation from the extracellular fluid, myo-inositol incorporation into inositol phospholipids, or total myo-inositol content. Chronic exposure of the cells to media containing 30 mmol/L glucose causes only a small increase in the intracellular sorbitol content. In contrast, chronic exposure of the cells to media containing 30 mmol/L galactose causes a large increase in galactitol content and a decrease in myo-inositol accumulation, myo-inositol incorporation into inositol phospholipids, and intracellular myo-inositol content. Sorbinil treatment of the galactose-supplemented media protects the cells form changes in myo-inositol metabolism and content. Chronic exposure of the cells to media containing 30 mmol/L glucose or 30 mmol/L galactose causes a decrease in ouabain-sensitive Na+/K(+)-ATPase transport activity, which is corrected by the addition of sorbinil to the media. Chronic exposure of the cells to media containing 45 mmol/L glucose, but not galactose, causes an increase in PGE2 production. These studies suggest that acute or chronic exposure of cultured microvessel endothelial cells to increased concentrations of glucose or galactose causes a decrease in myo-inositol uptake by different mechanisms. Chronic exposure of the cells to increased concentrations of glucose or galactose causes alterations in endothelial cell properties, including Na+/K(+)-ATPase transport activity and eicosanoid synthesis. The data are not clearly supportive of polyol accumulation and myo-inositol depletion as being responsible for the decrease in Na+/K+ pump activity.

Animals↗
PubMed1986

Transport of galactose and sodium across lizard duodenum.

Electrical parameters and transepithelial Na+ and galactose transport were determined in vitro across isolated duodenum of Lacerta galloti lizard. Electrical potential difference (PD) and short-circuit current (Isc) were dependent on the presence of Na+ in the bathing solutions. PD and Isc were affected by addition of galactose to the mucosal solution. Isotopic flux of Na+ measurements across short-circuited duodenum showed a net active Na+ absorption. The net flux of Na+ (JNa+net) accounted for the observed Isc. Both (JNa+net) and Isc were increased by the addition of galactose 5 mM to the mucosal solution. Isotopic flux galactose measurements in open-circuit conditions showed a net active galactose absorption. The net transport of galactose was decreased to zero in the absence of Na+ in mucosal and serosal reservoirs. Galactose has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of galactose concentration characterized by the parameters Vmax (maximum change in delta Isc) and Km (concentration needed to attain a velocity equal to half the Vmax).

Animals↗
PubMed1991

Galactose increases microvillus development in mouse jejunal enterocytes.

1. Mice fed low carbohydrate and galactose-containing diets have been used to determine both positional and temporal aspects of microvillus development during enterocyte migration from intestinal crypts towards the tips of jejunal villi. 2. The positional dependence of microvillus growth was found to be similar in mice fed low carbohydrate (3.0 kcal/g), galactose-containing lipid substituted (2.9 kcal/g) and galactose-containing agar substituted (5.1 kcal/g) diets. The daily calorific intake by mice fed these diets was about 10.4 kcal/mouse. The maximal microvillus length reached by enterocytes fed galactose was nearly twice that measured in mice fed the low carbohydrate diet. 3. Enterocyte migration rate in mice fed the low carbohydrate and the high calorie galactose-containing diet was twice that measured in mice fed the low calorie galactose-containing diet. These changes were not associated with any noticeable alteration in the size of intestinal crypts. 4. Changes in maximal microvillus length (M) can be predicted from the equation M = 0.0016 CD + 0.073 CD/R, where CD and R refer to crypt depth and enterocyte migration rate respectively, Smith M. W. and Brown D. (1989). Dual control over microvillus elongation during enterocyte development. Comp. Biochem. Physiol. 93A, 623-628. Substituting measured values for CD and R in this equation revealed a specific capacity of galactose to potentiate microvillus development when presented in the form of a high calorie diet. 5. The possibility that galactose, which is poorly metabolized in mice, can increase microvillus expression by interfering specifically with some aspect of carbohydrate metabolism is discussed.

Animals↗
PubMed1990

Transcriptional control by galactose of a yeast gene encoding a protein homologous to mammalian aldo/keto reductases.

Expression of the S. cerevisiae gene, GCY, encoding a 35-kDa protein with striking homology to mammalian aldo/keto reductases, is under the control of galactose: the intracellular concentration of the respective mRNA (about 1300 nt in length) varies strongly with the carbon source. It is particularly high when galactose is the sole energy source but is low as soon as glucose is present. Lactate, glycerol and raffinose lead to intermediate expression. Both Northern blot analyses and lacZ fusion data indicate a 20- to 50-fold increase in the steady state concentrations of mRNA and beta Gal activity, respectively, when grown on galactose as compared to glucose. The gene is derepressed after cultivation on glycerol in the wt and in a gal80 mutant background but remains uninducible by galactose in strains carrying either a gal2 or a gal4 mutation, affecting galactose permease and the GAL gene trans-activator, respectively. Analysis of GCY expression in gal regulatory mutants reveals epistasis interactions of the gal4 and the gal80 mutations as expected if GCY is regulated by the Gal control system. Repression of GCY transcription by glucose is observed in all three above gal mutant strains. The results suggest that the gene is both positively controlled by galactose and negatively by glucose. Analysis of a set of upstream deletions identifies a single UAS matching the consensus for GAL gene upstream regulation sites. By contrast to other genes regulated by galactose, disruption mutants of GCY exhibit no obvious phenotype, and in particular do not lose the ability to grow on and adapt to galactose. Enzyme tests with AKR-specific substrates suggest that GCY encodes a carbonyl reductase.

Base Sequence↗
PubMed2006

The adaptive filter of the yeast galactose pathway.

In the yeast Saccharomyces cerevisiae, the interplay between galactose, Gal3p, Gal80p and Gal4p determines the transcriptional status of the genes required for galactose utilization. After an increase in galactose concentration, galactose molecules bind onto Gal3p. This event leads via Gal80p to the activation of Gal4p, which then induces GAL3 and GAL80 gene transcription. Here we propose a qualitative dynamical model, whereby these molecular interaction events represent the first two stages of a functional feedback loop that closes with the capture of activated Gal4p by newly synthesized Gal3p and Gal80p, decreasing transcriptional activation and creating again the protein complex that can bind incoming galactose molecules. Based on the differential time-scales of faster protein interactions versus slower biosynthetic steps, this feedback loop functions as a derivative filter where galactose is the input step signal, and released Gal4p is the output derivative signal. One advantage of such a derivative filter is that GAL genes are expressed in proportion to cellular requirements. Furthermore, this filter adaptively protects the cellular receptors from saturation by galactose, allowing cells to remain sensitive to variations in galactose concentrations rather than to absolute concentrations. Finally, this feedback loop, by allowing phosphorylation of some active Gal4p, may be essential to initiate the subsequent long-term response.

Feedback, Physiological↗