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Metabolic energy and cytoskeletal requirements for synthesis and secretion by acini from rat mammary gland-II. Intracellular transport and secretion of protein and lactose.

1. Iodoacetate, 2,4-dinitrophenol, cyanide and cycloheximide inhibited protein secretion as well as synthesis by acini (alveoli) from rat mammary gland. Cytochalasin B and vinblastine inhibited protein secretion and marginally reduced protein synthesis. Colchicine was without effect on protein synthesis but inhibited secretion. 2. Intracellular protein transport was altered during incubation with metabolic and cytoskeletal inhibitors. Cycloheximide, iodoacetate. 2,4-dinitrophenol and cytochalasin B appeared to block protein synthesis on polysomes of rough endoplasmic reticulum. Vinblastine inhibited protein transport from rough endoplasmic reticulum to Golgi apparatus and colchicine appeared to cause accumulation of protein in several endomembrane fractions. 3. Iodoacetate reduced acinar lactose content but was without effect on lactose synthetase activity. Cyanide, cycloheximide and vinblastine reduced reduced lactose synthetase activity but not tissue lactose concentration. Cytochalasin B reduced glucose incorporation but was without effect on lactose content and lactose synthetase activity. Colchicine and 2,4-dinitrophenol did not alter glucose incorporation, lactose content or lactose synthetase activity. Lactose secretion was inhibited by all metabolic and cytoskeletal inhibitors examined. 4. Results indicated that sustained protein secretion depended on continued protein synthesis and that lactose secretion was coupled to protein secretion.

Animals↗

Voluntary lactose ingestion in gerbils, rats, mice, and golden hamsters.

Over a period of 20 days, adult male gerbils, rats, mice, and hamsters were allowed to choose between tap water and a sugar solution (either sucrose, glucose, or lactose) presented in increasing concentrations (maximum concentration = 24% weight/volume). Rats, mice, and hamsters preferred both glucose and sucrose solutions to water across a wide range of concentrations; gerbils preferred sucrose solutions at concentrations of 8% and above, but preferences for glucose solutions were not significant. Gerbils, mice, and rats did not prefer lactose solutions to water at any concentration, and actually preferred water at higher lactose concentrations; in contrast, hamsters preferred lactose solutions to water at concentrations of 4% and above, and never preferred water to lactose solutions. As solution concentrations increased, all species consumed increasing amounts of glucose and sucrose (i.e., solute). The lactose intake of gerbils, rats, and mice tended to remain quite low even as solution concentration increased; in contrast, the lactose intake of hamsters was substantially greater than that of other species and increased to a maximum of 1.95 g/100 g body weight/day at the 24% concentration. These results indicate that gerbils and mice, like rats, have a low preference for lactose and consume very little of this disaccharide, and confirm that golden hamsters are exceptional in demonstrating both a preference for lactose solutions and an apparent tolerance to the effects of ingestion of substantial amounts of lactose.

Animals↗

Absence of (Na+,K+)-ATPase involvement in lactose production by lactating guinea pig mammary gland.

The role of the (Na+, K+)-ATPase system in lactose production by the lactating guinea pig mammary gland has been studied in vitro with slices of the gland. In this system there is an initial fast lactose release, mainly representing secretion of preformed lactose, followed by a continuous slow lactose release, representing mainly lactose synthesis. The latter process occurs at a rate of 1.6 to 2.4 g lactose/kg wet wr/h, which value is about half of the lactose production in vivo (3.9 g/kg set wt/h). Incubation of slices in the presence of 10-4 M ouabain does not influence the rate of overall lactose production. When determined separately, it does not change either the rate of secretion or that of synthesis. This pleads against a role of the (Na+, K+)-ATPase system in lactose secretion or synthesis, in particular it seems to rule out control of the rates of these processes by the intracellular potassium concentration. An explanation for the generally observed correlation between the lactose and potassium concentrations in milk, may be that both the maintenance of the intracellular potassium concentration and the lactose synthesis rate require the presence of ATP.

Adenosine Triphosphatases↗

Crystallization and X-ray diffraction of spray-dried and freeze-dried amorphous lactose.

Crystallization of spray-dried and freeze-dried amorphous lactose over different relative vapor pressures (RVP) and storage times was studied. Crystallization was observed from increasing peak intensities in X-ray diffraction patterns. Lactose was crystallized in the samples stored at RVP of 44.1% and above in both types of dehydrated powders. The rate of crystallization increased with increasing RVP and storage time. Similar crystallization behavior of both spray-dried and freeze-dried lactose was observed. Lactose crystallized as alpha-lactose monohydrate, anhydrous beta-lactose, and the anhydrous form of alpha- and beta-lactose in a molar ratio of 5:3 and 4:1 in both spray-dried and freeze-dried forms. Peak intensities of X-ray diffraction patterns for anhydrous beta-lactose were decreased, and for alpha-lactose monohydrate increased with increasing storage RVP and time. The crystallization data were successfully modeled using Avrami equation at RVP of 54.5% and above. The crystallization data obtained is helpful in understanding and predicting storage stability of lactose-containing food and pharmaceutical products.

Crystallization↗

Formulation development of inhalation powders for FK888 with carrier lactose using Spinhaler and its absorption in healthy volunteers.

(4R)-4-Hydroxy-l-[(l-methyl-lH-indol-3-yl)carbonyl]-L-prolyl-N-benzyl-N-methyl-3-(2-naphthyl)-L-alaninamide (FK888) is a candidate selective NK1 receptor antagonist, and it exhibits poor absorption from the gastrointestinal (GI) tract in healthy volunteers. The objective of this study was to develop an optimized DPI formulation with carrier lactose using a Spinhaler, and thereby improve the systemic absorption of FK888. The fine particles of FK888 were blended with various carrier lactoses, and in vitro deposition properties were investigated using a twin impinger. The mixture using 100 M and 325 M lactoses [Sieved lactoses (SLs)] exhibited a higher emitted dose (Em) than 200 M, 450 M and micronized lactoses [Milled lactoses (MLs)]. The flowability of carrier lactose had an influence on the Em. On the other hand, the respirable particle (RP) fraction in the formulations with MLs was much higher than that of SLs, in spite of the blended ratios of lactose. It was also observed that the mixture of 325 M with the micronized lactose particles had the same RP as 200 M, although the 325 M alone had a low RP. Considering the Em and RP obtained, we chose 200 M for FK888 dry powder inhaler (DPI). The proportional absorption was found up to the 12.5% of the FK888 ratio (5 mg as unit dose) for the Cmax and AUC in healthy volunteers. In conclusion, 200 M, which has fine lactose particles and a better flowability than other MLs, is an extremely suitable carrier for maximizing the fine particle dose as far as FK888 is concerned. Furthermore, an improvement in the systemic absorption of FK888 was achieved using the dry powder formulations.

Absorption↗

Sonocrystallization: effect on lactose recovery and crystal habit.

Sonocrystallization is the use of power ultrasound to control the crystallization process, commonly used during the nucleation phase of crystallization. However, in the present study a different approach has been tried, in which the whole process of lactose crystallization from model reconstituted lactose solutions was completed rapidly with the aid of ultrasound, in the presence of 'ethanol' as an anti-solvent, at temperature of 30+/-2 degrees C (ambient temperature). The lactose recovery and crystal properties from sonicated samples were compared with non-sonicated samples. For optimization of sonocrystallization process for rapid lactose recovery, variations in the time of sonication, lactose concentration, protein concentration and pH were tried. A lactose recovery of 91.48% was obtained in 5 min of sonication time, from a reconstituted lactose solution (17.5% w/v, pH 4.2) as against 14.63% under only stirring. Lactose recovery decreased with lowering of pH from 4.2 to 2.8. The protein showed maximum influence on lactose recovery even at concentration of 0.2% w/v. A rapid process of crystallization gave a better uniformity in crystal size distribution of lactose samples.

Crystallization↗

A toxicological review of lactose to support clinical administration by inhalation.

Although lactose is widely used in the pharmaceutical industry as an excipient in preparations given by several routes of administration, including by inhalation, there is no comprehensive review of its toxicological properties. This document seeks to review the available oral preclinical and clinical safety data from the literature, together with that generated by Fisons in animals using the inhalation route. In animal toxicity studies, lactose has been administered primarily by the inhalation and dietary routes to the rat, dog and/or primate. Adverse findings, such as abdominal distension and diarrhoea, have been demonstrated in rodent feeding studies. However, these changes are considered to be due to non-specific effects associated with high dietary doses of lactose, with a subsequent production of a dietary imbalance which results in physiological disturbances and an overload in the metabolic processes particularly involving calcium. These changes at high dietary intakes of lactose are considered to be of little relevance for man under the normal conditions of use of the material as an excipient in pharmaceutical formulations. No adverse local effects to the lung have been demonstrated in the animal studies using the inhalation route. Although the inhalation dose of lactose in the animal studies, of which most is subsequently swallowed, is markedly higher than the clinical dose, it is considerably less than consumed in animal studies using the dietary route. Consequently, it is not surprising that lactose is well tolerated by the inhalation route. In a small number of susceptible humans, intolerance to lactose is generally observed with oral intake of lactose, usually as a constituent of milk and is associated with lactase deficiency. Swallowed lactose at the levels present in inhaled preparations is unlikely to present any significant problems in patients with lactase deficiency. In conclusion, lactose is well recognized as a safe pharmaceutical excipient for use in oral or inhalation formulations and is not likely to constitute any significant toxicological hazard to man.

Administration, Inhalation↗

Characterization of Glu126 and Arg144, two residues that are indispensable for substrate binding in the lactose permease of Escherichia coli.

Glu126 and Arg144 in the lactose permease are indispensable for substrate binding and probably form a charge-pair [Venkatesan, P., and Kaback, H. R. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 9802-9807]. Mutants with Glu126-->Ala or Arg144-->Ala do not bind ligand or catalyze lactose accumulation, efflux, exchange, downhill lactose translocation, or lactose-induced H+ influx. In contrast, mutants with conservative mutations (Glu126-->Asp or Arg144-->Lys) exhibit drastically different phenotypes. Arg144-->Lys permease accumulates lactose slowly to low levels, but does not bind ligand or catalyze equilibrium exchange, efflux, or lactose-induced H+ influx. In contrast, Glu126-->Asp permease catalyzes lactose accumulation and lactose-induced H+ influx to wild-type levels, but at significantly lower rates. Surprisingly, however, no significant exchange or efflux activity is observed. Glu126-->Asp permease exhibits about a 6-fold increase in the Km for active transport relative to wild-type permease with a comparable Vmax. Direct binding assays using flow dialysis demonstrate that mutant Glu126-->Asp binds p-nitrophenyl-alpha,D-galactopyranoside. Indirect binding assays utilizing substrate protection against [14C]-N-ethylmaleimide labeling of single-Cys148 permease reveal an apparent Kd of 3-5 mM for lactose and 15-20 microM for beta, D-galactopyranosyl-1-thio-beta,D-galactopyranoside (TDG). The affinity of Glu126-->Asp/Cys148 permease for lactose is markedly decreased (Kd > 80 mM), while TDG affinity is altered to a much lesser extent (Kd ca. 80 microM). The results extend the conclusion that a carboxylate at position 126 and a guanidinium group at position 144 are irreplaceable for substrate binding and support the idea that Arg144 plays a major role in substrate specificity.

Amino Acid Substitution↗

Mathematical model of the lac operon: inducer exclusion, catabolite repression, and diauxic growth on glucose and lactose.

A mathematical model of the lactose (lac) operon was developed to study diauxic growth on glucose and lactose. The model includes catabolite repression, inducer exclusion, lactose hydrolysis to glucose and galactose, and synthesis and degradation of allolactose. Two models for catabolite repression were tested: (i) cyclic AMP (cAMP) synthesis inversely correlated with the external glucose concentration and (ii) synthesis inversely correlated with the glucose transport rate. No significant differences in the two models were observed. In addition to synthesis, degradation and secretion of cAMP were also included in the model. Two models for the phosphorylation of the glucose produced from lactose hydrolysis were also tested: (i) phosphorylation by intracellular hexokinase and (ii) secretion of glucose and subsequent phosphorylation upon transport back into the cell. The latter model resulted in weak catabolite repression when the glucose produced from lactose was transported out of the cell, whereas the former model showed no catabolite repression during growth on lactose. Parameter sensitivity analysis indicates the importance of key parameters to lac operon expression and cell growth: the lactose and allolactose transformation rates by beta-galactosidase and the glucose concentrations that affect catabolite repression and inducer exclusion. Large values of the allolactose hydrolysis rate resulted in low concentrations of allolactose, low-level expression of the lac operon, and slow growth due to limited import and metabolism of lactose; small values resulted in a high concentration of allolactose, high-level expression of the lac operon, and slow growth due to a limiting concentration of glucose 6-phosphate formed from allolactose. Changes in the rates of all beta-galactosidase-catalyzed reactions showed similar behavior, but had more drastic effects on the growth rate. Changes in the glucose concentration that inhibited lactose transport could extend or contract the diauxic growth period during growth in the presence of glucose and lactose. Moreover, changes in the glucose concentration that affected catabolite repression affected the cAMP levels and lac operon expression, but had a lesser effect on the growth rate.

Biological Transport↗

Identification of N-acetyl-4-O-acetylneuraminyl-lactose in Echidna milk.

The identity of a novel form of sialyl-lactose found in milk of the echidna (Tachyglossus aculeatus) was investigated. The sialyl-lactose yielded equimolar amounts of N-acetylneuraminic acid and lactose during mild acid hydrolysis but was resistant to the action of a bacterial neuraminidase. A viral neuraminidase hydrolysed it to lactose plus a form of sialic acid that reacted positively with thiobarbituric acid reagent but whose chromatographic mobility was greater than that of N-acetylneuraminic acid. Treatment with alkali converted the sialyl-lactose into a substance with the same chromatographic mobility as N-acetylneuraminyl-(2-->3)-lactose and made it susceptible to the action of bacterial neuraminidase. The sialyl-lactose contained one mol of ester (identified as acetyl), and released one mol of formaldehyde during periodate oxidation, per mol of sialic acid. It did not contain N-glycollylneuraminic acid. These results indicate that the sialyl-lactose is N-acetyl-4-O-acetylneuraminyl-(2-->3)-lactose. Echidna milk contained, in addition, a small amount of N-acetylneuraminyl-(2-->3)-lactose.

Animals↗

Ovarian effects of a high lactose diet in the female rat.

Young women with galactosemia experience ovarian failure at a very early age raising concern about the ovarian toxicity of galactose. While galactose may be present in the diet as a monosaccharide, it is predominantly derived from cleavage of the disaccharide lactose within the intestine. Our previous studies in animals have shown that high galactose diets inhibit ovarian follicular development and long-term exposure to high lactose diets retards growth of rats. The objective of the present study was to determine whether galactose exposure in the form of dietary lactose mimics the effects found previously with diets rich in galactose. Sixty female Long-Evans rats (25-day-old) were randomly assigned to two groups and fed a control diet (41.9% glucose in AIN93G [American Institute of Nutrition], CON) before lactose treatment. Unilateral ovariectomy (uOVX) was performed on half of the rats in each group to determine baseline ovarian follicle numbers. The study diet was a high lactose diet (HLD) containing 41.9% lactose in AIN93G. Study diet exposure started 1 month after uOVX (3 months old) and continued for 7 months in the treatment group. The control group remained on the 41.9% glucose diet throughout. Vaginal cytology, ovarian morphometric analyses, and serum concentrations of estradiol and progesterone were examined. Long-term exposure to the HLD decreased the body weights of animals and progesterone concentrations in the serum but produced no harmful effects on ovarian morphology or function. Beginning at 5 months of age (two months of lactose treatment) increasing numbers of females began to cycle irregularly but there was no difference between the glucose and lactose diet groups. These negative findings imply that administration of galactose in the form of lactose seems to be much less toxic than when galactose is fed to animals. From a human health perspective, these results are somewhat reassuring, since in general, women eat lactose-containing foods rather than foods that contain large amounts of free galactose.

Aging↗

Progesterone control of the initiation of lactose synthesis in the rat.

The in vitro incorporation of [14c]glucose into lactose in mammary tissue, the concentration of lactose in the mammary tissue and the concentration of lactose in the mammary secretion were determined during late pregnancy and lactation in the rat. These changes were related to the decline in blood progesterone during late pregnancy. The incorporation of [14C]glucose into lactose was detected on day 20 of pregnancy; it increased gradually until day 22 and then increased rapidly just prior to term (day 23 of pregnancy) to reach mean +/- s.e.m. maximum hourly values of 12.0 +/- 1.5 cpm x 10(4)/g by day 3 of lactation, and then declined to lower values (6.1 +/- 0.6 cpm x 10(4)/g) by day 20 of lactation. The concentration of lactose in both in the mammary tissue and in the mammary secretion increased rapidly over the last 24h of pregnancy and then more gradually after birth to reach mean +/- s.e.m. maximum values of 6.85 +/- 1.11 mg/g tissues and 43.1 +/-0 2.1 g/l respectively on day 15 of lactation. The decline in plasma progesterone to low levels between days 21 and 22 of pregnancy preceded the rapid increase in the concentration of lactose in the mammary tissue. A similar relationship was observed between the decline in progesterone and the increase in lactose in mammary tissue in rats Caesarean-sectioned on day 19 of pregnancy, and the administration of progesterone immediately following Caesarean section significantly depressed the accumulation of lactose in the mammary tissue. The results support the involvement of progesterone withdrawal in lactogenesis in the rat and indicate that [14C]glucose incorporation into lactose and the concentration of lactose both in the mammary tissue and in mammary secretion are useful indicators of the synthetic activity of the mammary gland.

Animals↗

Urinary excretion of magnesium and calcium as an index of absorption is not affected by lactose intake in healthy adults.

The effect of lactose on the urinary excretion of Mg and Ca, as an index of absorption, was studied in a double-blind, crossover study during three 1-week periods. Twenty-four healthy, lactose-tolerant, adult volunteers maintained their habitual diets with the exception that all lactose-containing dairy products in the diet were replaced by 600 g/d of three specially prepared dairy products. These products were based on either lactose-enriched cow's milk or lactose-enriched, lactase (EC 3.2.1.23)-treated cow's milk, with or without added Mg, and were given in turn during 1 week. Lactose intake was increased by 127 mmol/d (46 g/d) while taking the lactose-enriched products. While taking the Mg-enriched products, Mg intake was increased by 2.8 mmol/d (69 mg/d) which was equivalent to 17% of the habitual Mg intake. Apart from the lactose and Mg intake, nutrient intake was comparable during the three dietary periods. Urinary excretions of Mg and Ca were used as indicators for their absorption. Mg supplementation significantly increased urinary Mg excretion by 0.97 mmol/d (equivalent to an increase of 18%, P < 0.001), indicating that urinary Mg excretion is a valid indicator for intestinal Mg absorption. Hydrolysis of lactose did not affect urinary excretion of Mg and Ca, which implies that lactose intake does not affect the absorption of Mg and Ca in healthy adults.

Adult↗

The responses of blood galactose to oral doses of lactose, galactose plus glucose and milk to piglets.

The capacity of intestinal lactase (EC 3.2.1.23) of piglets to hydrolyse lactose in vivo was investigated by measuring the response of blood galactose to doses of lactose, galactose plus glucose and both whole and skimmed milk. Following the administration of oral doses of lactose dissolved in water to piglets from 2 to 18 d of age the adjusted galactose area under the curve (AUC) was between 1.12 and 1.36 arbitrary units, while following a dose of galactose plus glucose dissolved in water it was between 1.56 and 1.98 arbitrary units. Whereas these results suggest that the rate of digestion of lactose appeared to limit the amount of galactose reaching the peripheral blood after a dose of lactose dissolved in water, there was no significant correlation between the capacity of piglets to hydrolyse physiological amounts of lactose and the age of the piglets (2- to 18-d-old piglets; r 0.11). Following oral doses of sow's milk containing either lactose, or galactose plus glucose, the adjusted galactose AUC values were 0.94 and 1.00 arbitrary units respectively, in 10-d-old piglets. Thus, the limitation to the digestion of lactose observed when it was present in water was not evident for lactose in sow's milk. Since there was no significant difference between the adjusted galactose AUC following a dose of whole milk (0.95 arbitrary units) and that following a dose of skimmed milk (1.03 arbitrary units), the presence of fat in sow's milk did not appear to affect the utilization of lactose by the sucking piglets.

Animals↗

Lactose malabsorption and rate of bone loss in older women.

OBJECTIVES: to study the prevalence of lactose malabsorption with increasing age and to determine whether lactose malabsorbers consume less dietary calcium, have lower bone mineral density or display faster bone loss than lactose absorbers. DESIGN: 80 healthy Caucasian women aged 40-79 years (20 per decade) were studied for 1 year. METHODS: breath hydrogen exhalation was measured for 3 after a 50 g oral lactose challenge. Bone density was assessed in the radius, femoral neck, lumbar spine and total body by dual energy x-ray absorptiometry and dietary calcium intake was estimated by 4-day diet records and food-frequency questionnaires. RESULTS: lactose malabsorption rose with age (15% in those aged 40-59 years versus 50% in those aged 60-79; P < 0.01). Malabsorbers aged 70-79 years consumed significantly less calcium than lactose absorbers of this age (P < 0.05). Baseline total body calcium values were lower in lactose malabsorbers (n=26) than in lactose absorbers (n=54) but age-adjustment eliminated this difference. Bone change (% per year) was correlated with dietary calcium intake at the femoral neck and trochanter (P < 0.05) but was not statistically greater in malabsorbers than in absorbers. CONCLUSIONS: the ability to absorb lactose declines in the 7th decade. This may contribute to decreased dietary intakes of milk products and calcium in elderly women. However, lactose malabsorption without reduction in calcium intake has little effect on bone mineral density or the rate of bone loss.

Adult↗

Lactose, calcium source and age affect calcium bioavailability in rats.

Calcium bioavailability was defined as either retention of 45Ca in tibias (Experiment 1) or retention of 47Ca in carcasses (Experiment 2). In Experiment 1, rats (age 21, 40 or 100 d) were fed purified meals extrinsically labeled with 45Ca. The meals contained either 0.5% Ca (control) or 1% Ca [control supplemented with CaCO3, calcium citrate-malate (CCM), milk or cheese] and either no lactose or 20% lactose. Lactose increased Ca bioavailability (P less than 0.05) from the control and milk meals in all age groups. Increases from CCM and CaCO3 were significantly only in the 21-d-old group. Lactose did not affect bioavailability from cheese. In Experiment 2, suckling rats (age 7, 12 or 17 d) were gavaged with 47Ca-labeled milk (fluid skim or lactose-hydrolyzed fluid skim) or an aqueous CaCl2-casein mixture (containing either no sugar, glucose + galactose, or lactose). Bioavailability from milk was higher than from lactose-hydrolyzed milk in all age groups. Lactose and glucose + galactose increased bioavailability over the sugar-free CaCl2-casein mixture in all age groups. Data from these experiments show that lactose enhances Ca bioavailability at several stages of development and the effect is not markedly diminished by high Ca diets. Lactose increases Ca bioavailability from a variety of sources but the magnitude of the effect may vary among sources.

Aging↗

Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation.

An investigation was carried out on 61 children suffering from symptomatic giardiasis with the object of verifying the incidence and entity of lactose malabsorption. Furthermore, the possibility of a substitutive yogurt diet was verified in the lactose malabsorbers. The subjects, all children older than 1 year, were studied according to a schedule that included a lactose hydrogen breath test (BT) performed prior to therapy and a further BT 60 days following therapy. The subjects were divided in two groups: group A, 40 children, received a dose of 250 ml of cow's milk; group B, 21 children, received a stress dose of 2 g/kg lactose (max 50 g). Those subjects who were lactose malabsorbers at the 60 day follow-up were also given a BT at 75 days, and in the case of persistent malabsorption, a further BT was performed after 24 h with the administration of yogurt (450 g containing 12.1 g of lactose). Furthermore, 40 subjects matched for age and sex but without any GI complaints served as controls. The results showed lactose malabsorption to be frequent in children with Giardia lamblia symptomatic infection. According to the BT with a standard lactose load, all patients were malabsorbers; when testing lactose absorption with 250 ml of cow's milk, 45% of patients were found to be malabsorbers. In the latter subjects, the oral load of yogurt was uniformly well tolerated and gave rise to no H2 increment on the BT. We conclude that the occurrence of lactose malabsorption of nutritional relevance is common in children suffering or having suffered from giardiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Genetics of lactose utilization in lactic acid bacteria.

Lactose utilization is the primary function of lactic acid bacteria used in industrial dairy fermentations. The mechanism by which lactose is transported determines largely the pathway for the hydrolysis of the internalized disaccharide and the fate of the glucose and galactose moieties. Biochemical and genetic studies have indicated that lactose can be transported via phosphotransferase systems, transport systems dependent on ATP binding cassette proteins, or secondary transport systems including proton symport and lactose-galactose antiport systems. The genetic determinants for the group translocation and secondary transport systems have been identified in lactic acid bacteria and are reviewed here. In many cases the lactose genes are organized into operons or operon-like structures with a modular organization, in which the genes encoding lactose transport are tightly linked to those for lactose hydrolysis. In addition, in some cases the genes involved in the galactose metabolism are linked to or co-transcribed with the lactose genes, suggesting a common evolutionary pathway. The lactose genes show characteristic configurations and very high sequence identity in some phylogenetically distant lactic acid bacteria such as Leuconostoc and Lactobacillus or Lactococcus and Lactobacillus. The significance of these results for the adaptation of lactic acid bacteria to the industrial milk environment in which lactose is the sole energy source is discussed.

Gene Expression Regulation, Bacterial↗