Tryptophan Transport Research Articles

Serotoninergic status in patients with hereditary vascular retinopathy syndrome

AIM/BACKGROUNDIn a new autosomal dominant syndrome (which the authors called hereditary vascular retinopathy (HVR)) cerebral ischaemia, Raynaud’s phenomenon, and migraine are the most striking features. As serotonin (5-HT) is known...

Inhibition of Amino Acid Transport by Sphingoid Long Chain Bases in Saccharomyces cerevisiae

Sphingoid long chain bases have many effects on cells including inhibition or stimulation of growth. The physiological significance of these effects is unknown in most cases. To begin to understand how these compounds inhibit growth, we have studied Saccharomyces cerevisiae cells. Growth of tryptophan (Trp-) auxotrophs was more strongly inhibited by phytosphingosine (PHS) than was growth of Trp+ strains, suggesting that PHS diminishes tryptophan uptake and starves cells for this amino acid. This hypothesis is supported by data showing that growth inhibition is relieved by increasing concentrations of tryptophan in the culture medium and by multiple copies of the TAT2 gene, encoding a high affinity tryptophan transporter. Measurement of tryptophan uptake shows that it is inhibited by PHS. Finally, PHS treatment induces the general control response, indicating starvation for amino acids. Multiple copies of TAT2 do not protect cells against two other cationic lipids, stearylamine, and sphingosine, indicating that the effect of PHS on tryptophan utilization is specific. Other data demonstrate that PHS reduces uptake of leucine, histidine, and proline by specific transporters. Our data suggest that PHS targets proteins in the amino acid transporter family but not other distantly related membrane transporters, including those necessary for uptake of adenine and uracil.

Interactions between thyroid hormone and tryptophan transport in rat liver are modulated by thyroid status.

We have identified both N-ethylmaleimide (NEM)-resistant (system T) and NEM-sensitive (system L1) L-[3H]tryptophan transporters in sinusoidal membrane vesicles (SMVs) from euthyroid, hypothyroid (propylthiouracil-treated), and hyperthyroid [L-3,5,3'-triiodothyronine (L-T3)-injected] rats. L-[125I]T3 associates with SMVs largely by surface binding. Kinetic characteristics of tryptophan uptake and T3 binding (transporter or receptor abundance and substrate affinity) are not significantly affected by thyroid status. T3 and thyroxine (T4) inhibit NEM-resistant tryptophan uptake in SMVs to an extent dependent on the thyroid status of the donor rat, increasing in the order hypothyroid < euthyroid < hyperthyroid; the inhibitor constant for this inhibition (0.3 microM T3) is equal to the dissociation constant for T3 binding. Both T3 binding and T3 inhibition of tryptophan transport in SMVs are markedly reduced by treatments (Triton X-100 or trypsin) that do not significantly affect vesicle integrity or transport of tryptophan and glucose. T3 and/or T4 transport at the liver-plasma interface may be facilitated by direct interactions between hormone receptors and system T transporter proteins. Modulation of such interactions may be important for control of hepatic T4 and/or T3 turnover and aromatic amino acid metabolism during altered thyroid status.

A topological model for the general aromatic amino acid permease, AroP, of Escherichia coli.

The general aromatic amino acid permease, AroP, of Escherichia coli is responsible for the active transport of phenylalanine, tyrosine, and tryptophan. A proposed topological model for the AroP permease, consisting of 12 hydrophobic transmembrane spans connected by hydrophilic loops, is very similar to that of the closely related phenylalanine-specific permease. The validity of this model and its similarity to that of the PheP permease were investigated by studying fusion proteins of AroP permease and alkaline phosphatase. Based on the results obtained from the AroP-alkaline phosphatase sandwich fusions, we have significantly revised the proposed topological model for AroP in two regions. In this modified AroP topological model, the three charged residues E151, E153, and K160 are repositioned within the membrane in span 5. These three residues are conserved in a large family of amino acid transport proteins, and site-directed mutagenesis identifies them as being essential for transport activity. It is postulated that these residues together with E110 in transmembrane span 3 may be involved in a proton relay system.

Tyrosine uptake and regional brain monoamine metabolites in a rat model resembling congenital hyperammonemia.

Hyperammonemia found in congenital disorders has a toxic effect on the central nervous system. Disturbances of brain neurotransmitter metabolism have been proposed, such as an increased transport of tryptophan into the brain and an increased flux through the serotonin pathway. Results concerning the catecholamine pathway are, however, contradictory. We therefore studied whether hyperammonermia increases brain uptake of the neurotransmitter precursor amino acid tyrosine and whether these changes affect the concentration of neurotransmitters and their metabolites in different brain areas (frontal cortex, caudatus-putamen, thalamus, hypothalamus, hippocampus/substantia nigra, brainstem) of rats made hyperammonemic with urease. The brain uptake of tyrosine was measured in the forebrain, brainstem, and cerebellum. The brain areas were analyzed for dopamine, 3,4-hydroxyphenylacetic acid; homovanillic acid, norepinephrine, and vanillylmandelic acid. The brain uptake index of tyrosine was increased in the forebrain and brainstem of the hyperammonemic rats with concomitantly elevated concentrations in the forebrain of tyrosine, phenylalanine, and tryptophan. The homovanillic acid content was significantly increased in the hypothalamus, hippocampus/substantia nigra and brainstem. The concentrations of norepinephrine, dopamine, and 3, 4-hydroxyphenylacetic acid were not significantly changed. Vanillylmandellic acid was decreased in the caudatus-putamen, thalamus, and hypothalamus. The data indicate an undisturbed neurotransmitter synthesis and, taken with the augmented tyrosine uptake at the blood-brain barrier, an increased flux through the dopamine pathway. These changes observed in the hyperammonemic animal model could contribute to the understanding of the pathogenic mechanisms and offer an explanation for the neuropsychiatric disturbances observed in children with congenital hyperammonemia.

Serotonin-dopamine interaction and its relevance to schizophrenia.

The therapeutic success of clozapine and risperidone has focused attention on the interaction between serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance. The authors synthesized information from more than 100 published articles obtained through electronic and bibliography-directed searches. The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symptoms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with doses that produce suprathreshold dopaminergic blockade. Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.

A review of the evidence that ultraviolet irradiation is a risk factor in cataractogenesis.

There are two approaches to the question of whether solar radiation contributes to human cataract. The first, epidemiological studies, investigates correlations between man's environmental UV dose and cataract frequency. The second, animal models, investigates the effects of varying UV strengths and spectra on lens opacification in vivo or in vitro. While the latter approach typically provides for direct evidence, the data must still be extrapolated to human lenses. Results of physiological studies suggest that UV photons interact with proteins of the epithelial cell membranes, in particular tryptophan residues, transport ATPases and cytoskeletal proteins. One hypothesis is that damage to ion pumps and channels accumulates over the years as repair processes incompletely restore membrane function. Peroxidative damage is likely in view of the formation of UV-induced lipid peroxides in the lens epithelial membranes. Loss of homeostatic control of ions, particularly Ca++, leads to crystallin disorder in small regions of the underlying fiber cells. In our diabetic cataract studies, intracellular Ca++ electrodes detected large shifts in intracellular Ca++ before bulk-lens changes were apparent. Similar occurrences likely characterize UV cataract. Our lab is one of few studying lens physiology and how it is altered following transient exposures to UV-B and UV-A, both of which pass through the cornea. Some changes include: loss of epithelial cell GSH; elevated Ca++; loss of membrane voltage; impaired transport of Na+; increased permeability to ions and water; inhibition of critical enzymes; and a decrease in the rate of membrane synthesis.

Effect of aging on the kinetics of blood-brain barrier uptake of tryptophan in rats.

The purpose of this investigation was to examine the effect of aging on the blood-brain barrier (BBB) transport of tryptophan. A well established in-situ brain perfusion technique was used to examine brain uptake of 14C-tryptophan in 2-, 12- and 24-month old Sprague-Dawley rats; perfusate tryptophan concentrations ranged from 0.00175 to 2 mM. Uptake data were modeled using non-linear regression analysis. Permeability-surface area product (PA) for tryptophan was significantly lower in 12- and 24-month old rats, as compared to the 2-month old animals. A transport model consisting of both saturable (Michaelis-Menten type) and non-saturable components best described brain uptake of tryptophan in all 3 age groups. However, age-dependent differences in BBB transport parameters of tryptophan were observed. For the saturable component, both Vmax and Km were significantly lower in the 12- and 24-month old rats, as compared to the youngest group of rats. These results suggest that transporter mobility, number and affinity for tryptophan are altered in older rats. Values for Kd, the rate constant for non-saturable brain tryptophan transport, were also significantly lower in animals of the two older age groups. Interestingly, PA values for thiourea, a compound believed to be transporter across BBB by diffusion, were also lower in these two age groups. Aging decreases the ability of the BBB to transport the neutral amino acid tryptophan.

Enhancing central and peripheral insulin activity as a strategy for the treatment of endogenous depression — An adjuvant role for chromium picolinate?

Depression is often associated with insulin resistance, owing to cortisol overproduction; conversely, many studies suggest that diabetics are at increased risk for depression. Recent evidence indicates that insulin is transported through the blood-brain barrier and influences brain function via widely distributed insulin receptors on neurons. These receptors are particularly dense on catecholaminergic synaptic terminals, and, while effects are variable dependent on brain region, several studies indicate that insulin promotes central catecholaminergic activity, perhaps by inhibiting synaptic re-uptake of norepinephrine. Additionally, it is well known that insulin enhances serotonergic activity in increasing blood-brain barrier transport of tryptophan. Since impaired monoaminergic activity in key brain pathways is believed to play an etiological role in depression, techniques which promote effective insulin activity, both centrally and peripherally, may be therapeutically beneficial in this disorder. This may rationalize anecdotal reports of improved mood in clinical depressives and diabetics receiving the insulin-sensitizing nutrient chromium picolinate. This nutrient, perhaps in conjunction with other insulin-sensitizing measures such as low-fat diet and aerobic exercise training (already shown to be beneficial in depression), should be tested as an adjuvant for the treatment and secondary prevention of depression.

Interactions between transport of triiodothyronine and tryptophan in JAR cells

We studied the effect of a number of amino acids on uptake of l-triiodothyronine (T 3) in the human choriocarcinoma cell line, JAR. Tryptophan inhibited saturable T 3 uptake by about 57% without any significant effect on the non-saturable uptake. Michaelis constant ( K m) for T 3 uptake was 1.06 ± 0.15 μM ( n = 15) with the corresponding maximum velocity ( V max) of 24.2 ± 3.1 pmol/min/mg cellular protein. For tryptophan uptake the K m was 1.31 ± 0.26 μM ( n = 7) and V maxpmol/min/mg protein. The kinetic parameters for both uptake processes were similar to those reported in normal placenta. Uptake of T 3 was inhibited by tryptophan but not phenylalanine, but tryptophan uptake was inhibited both by T 3 and phenylalanine. Inhibition of T 3 uptake by tryptophan was dose dependent, with an inhibition constant ( K i) of 2.9 ± 0.5 mM. Similarly, tryptophan uptake was inhibited by T 3 and phenylalanine in a dose dependent way with K i values of 4.9 ± 0.5 μM a 15.6 ± 4.8 μM respectively. K m for T 3 uptake was significantly increased to 1.86 ± 0.42 μM ( n = 4) in the prese unlabelled tryptophan and, similarly, K m for tryptophan uptake was significantly increased to 9.91 ± 2.57 μM ( n = 3) in the presence of 5 μM unlabelled T 3. Efflux of T 3 was progressively inhibited by increasing concentrations of both ligands i.e. was saturable. We conclude that there is mutual competitive inhibition between uptake systems for T 3 and tryptophan in JAR cells, but the kinetic parameters of cross-inhibition of uptake by the substrates suggest that the carriers are distinct. T 3 may be transported in JAR cells by at least two transport systems with differing substrate specificities. We also demonstrated the presence of a saturable membrane carrier mediating the efflux of T 3 from the cells which was subject to trans-inhibition by T 3 and tryptophan.

Mutational analysis of the traffic ATPase (ABC) transporters involved in uptake of eye pigment precursors in Drosophila melanogaster. Implications for structure-function relationships.

The white, brown, and scarlet genes of Drosophila melanogaster encode three proteins that belong to the Traffic ATPase superfamily of transmembrane permeases and are involved in the transport of guanine and tryptophan (precursors of the red and brown eye pigments). We have determined the nucleotide sequences of two mutant white alleles (wco2 and wBwx) that cause reduced red pigmentation but have no effect on brown pigmentation. In wco2 the effect is only observed when interacting with the bw6 allele or a newly isolated allele (bwT50). These alleles of the brown gene were cloned and sequenced. In wco2 the codon for glycine 588 is changed to encode serine; in wBwx the triplet ATC encoding isoleucine 581 is deleted; asparagine 638 is changed to threonine in bw6, and glycine 578 is changed to aspartate in bwT50. No other relevant changes to the gene structures were detected. P-element-mediated germline transduction was used to construct a fly strain containing a white gene with a mutation of the nucleotide binding domain. Such flies had white eyes, indicating that the mutated white gene was unable to support either guanine or tryptophan transport. The implications of these mutations are discussed in terms of a model of the Drosophila pigment precursor transport system.

Effects of a competitive triathlon on plasma concentrations of tryptophan and branched-chain amino acids

The aim of this work was to determine the acute responses of tryptophan and branched chain amino acids to a triathlon competition. Fourteen male triathletes were studied. All took part in a international triathlon race consisting of 1,5 km swimming, 40 km biking and 10 km running. Venous blood samples were drawn before (-24 h) and after (15 min) the triathlon. Plasma concentration of branched chain amino acids and total and free tryptophan were determined. Branched chain amino acids decreased from 463 - 108.3 to 364 - 98.9 mol/L (p < 0.03). Free tryptophan increases from 9.2 to 16.3 mol/L (p < 0.006). Furthermore the ratio of free trytophan to branched chain amino acids increased from 2.07 - 0.48 to 4.24 - 0.79 (p < 0.001). This increases the rate of transport of tryptophan accross the blood-brain barrier and also increases the rate of synthesis of 5-hydroxytryptamine in the central nervous system. A high presence of 5-hydroxytryptamine in the brain develops physical and mental fatigue during the triathlon. This data support the participation of amino acids in fatigue process during triathlon

Quinolinic acid in children with congenital hyperammonemia.

Levels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammonemia. Twofold to tenfold elevations of QUIN were found in 4 neonates in hyperammonemic coma (QUIN range, 250-990 nM; control mean, 110 +/- 90 nM; p < 0.005). Similar elevations of neopterin were found (range, 24-75 nM; control mean, 9.0 +/- 4.9 nM; p < 0.005). In addition, significant elevations of QUIN were found in 14 older children with congenital hyperammonemia (mean, 50 +/- 20 vs 17 +/- 6 nM; p < 0.05). Neopterin levels were not elevated in these children. The QUIN may originate from an increase in tryptophan transport across the blood-brain barrier or from induction of indolamine-2,3-dioxygenase activity. These findings support a role for QUIN in the neuropathology of congenital hyperammonemia. They also suggest the potential utility of N-methyl-D-aspartate receptor-blocking agents or inhibitors of QUIN synthesis in the treatment of hyperammonemic coma.

AOT reversed micelles as carriers of amino acids across liquid membranes. Search for selectivity and chirality effect

Reversed micelles of diethylhexyl sodium sulphosuccinate (AOT) are used in this work as mobile carriers to transport amino acids between a source (S) and a receiving (R) aqueous phase across an organic liquid membrane (M) (isooctane). For most experiments the aqueous and organic phases were those of a pre-equilibrated Winsor II system. Semipermeable membranes have been introduced between the S and M phases as well as between the M and R phases for technical reasons. The rates of transport of p-iodophenylalanine and tryptophan were compared and discussed in relation to their partition coefficients between water and the AOT palisade layer, showing completely different behaviour between the two amino acids. As the selectivity of the transport process may depend on the water content of the membrane phase and also on the carrier/solute interactions, we have investigated the rate of water uptake by the AOT reversed micelles as well as the influence of the ionization state of amino acids. The last part of the work is concerned with an attempt to perform enantioselective transports using chiral AOT. The analysis of the receiving phase required in that case a chromatographic resolution of amino acid enantiomers. This resolution was affected by the nature of the background salt, which had to be specifically adapted for this purpose. The failure of these experiments in producing enantiomeric enrichments suggests that the rigidity of the surfactant film is not sufficient to permit chiral recognition in that case.

The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.

The immunosuppressants cyclosporin A, FK506, and rapamycin inhibit growth of unicellular eukaryotic microorganisms and also block activation of T lymphocytes from multicellular eukaryotes. In vitro, these compounds bind and inhibit two different types of peptidyl-prolyl cis-trans isomerases. Cyclosporin A binds cyclophilins, whereas FK506 and rapamycin bind FK506-binding proteins (FKBPs). Cyclophilins and FKBPs are ubiquitous, abundant, and targeted to multiple cellular compartments, and they may fold proteins in vivo. Previously, a 12-kDa cytoplasmic FKBP was shown to be only one of at least two FK506-sensitive targets in the yeast Saccharomyces cerevisiae. We find that a second FK506-sensitive target is required for amino acid import. Amino acid-auxotrophic yeast strains (trp1 his4 leu2) are FK506 sensitive, whereas prototrophic strains (TRP1 his4 leu2, trp1 HIS4 leu2, and trp1 his4 LEU2) are FK506 resistant. Amino acids added exogenously to the growth medium mitigate FK506 toxicity. FK506 induces GCN4 expression, which is normally induced by amino acid starvation. FK506 inhibits transport of tryptophan, histidine, and leucine into yeast cells. Lastly, several genes encoding proteins involved in amino acid import or biosynthesis confer FK506 resistance. These findings demonstrate that FK506 inhibits amino acid import in yeast cells, most likely by inhibiting amino acid transporters. Amino acid transporters are integral membrane proteins which import extracellular amino acids and constitute a protein family sharing 30 to 35% identity, including eight invariant prolines. Thus, the second FK506-sensitive target in yeast cells may be a proline isomerase that plays a role in folding amino acid transporters during transit through the secretory pathway.

Inhibition of expression of the tryptophanase operon in Escherichia coli by extrachromosomal copies of the tna leader region.

Expression of the tryptophanase (tna) operon in Escherichia coli is regulated by catabolite repression and transcription attenuation. Expression is induced by the presence of elevated levels of tryptophan in a growth medium devoid of a catabolite-repressing carbon source. Induction requires the translation of a 24-residue coding region, tnaC, located in the 319-nucleotide transcribed leader region preceding tnaA, the structural gene for tryptophanase. Multicopy plasmids carrying the tnaC leader region were found to inhibit induction of the chromosomal tna operon. Mutational studies established that this inhibition was not due to inhibited transcription initiation, translation initiation, tryptophan transport, or enzyme activity. Rather, multicopy tnaC plasmids inhibited induction by preventing tryptophan-induced transcription antitermination in the leader region of the tna operon. Translation of the single Trp codon in tnaC of the multicopy plasmids was shown to be essential for this inhibition. We hypothesize that translation of the Trp codon of the leader peptide titrates out a trans-acting factor that is essential for tryptophan-induced antitermination in the chromosomal tna operon. We postulate that this factor is an altered form of tRNATrp.

Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy.

Liver failure, or shunting of intestinal blood around the liver, results in hyperammonemia and cerebral dysfunction. Recently it was shown that ammonia caused some of the metabolic signs of hepatic encephalopathy only after it was metabolized by glutamine synthetase in the brain. In the present study, small doses of methionine sulfoximine, an inhibitor of cerebral glutamine synthetase, were given to rats either at the time of portacaval shunting or 3-4 weeks later. The effects on several characteristic cerebral metabolic abnormalities produced by portacaval shunting were measured 1-3 days after injection of the inhibitor. All untreated portacaval-shunted rats had elevated plasma and brain ammonia concentrations, increased brain glutamine and tryptophan content, decreased brain glucose consumption, and increased permeability of the blood-brain barrier to tryptophan. All treated rats had high ammonia concentrations, but the brain glutamine content was normal, indicating inhibition of glutamine synthesis. One day after shunting and methionine sulfoximine administration, glucose consumption, tryptophan transport, and tryptophan brain content remained near control values. In the 3-4-week-shunted rats, which were studied 1-3 days after methionine sulfoximine administration, the effect was less pronounced. Brain glucose consumption and tryptophan content were partially normalized, but tryptophan transport was unaffected. The results agree with our earlier conclusion that glutamine synthesis is an essential step in the development of cerebral metabolic abnormalities in hyperammonemic states.

Distribution of mRNA of a Na(+)-independent neutral amino acid transporter cloned from rat kidney and its expression in mammalian tissues and Xenopus laevis oocytes.

The Na(+)-independent neutral amino acid transporter (NAA-Tr) that we had previously cloned from rat kidney has been investigated with respect to its distribution in mammalian tissues and cells. By Northern blot analysis and RNase protection assay, a 2.4-kilobase (kb) mRNA in rat intestine was found to be identical to that in rat kidney. Of the other rat tissues examined, only brain and heart were found to contain mRNAs related to kidney NAA-Tr by Northern assay. However, these were larger (approximately 5 and approximately 7 kb). Mouse and rabbit kidney also contain mRNAs of 2.4 kb that exhibited a high degree of homology with rat kidney NAA-Tr. Of the several cultured cells investigated that demonstrated considerable Na(+)-independent neutral amino acid transport activity, only human colon carcinoma (Caco) cells were positive by Northern assay. The failure to detect NAA-Tr mRNA in many cells and tissues that carry out Na(+)-independent transport indicates that unrelated transporters must also exist. Cells and tissues that were negative with respect to rat kidney NAA-Tr as well as those that were positive transported leucine and tryptophan equally well. However, when mRNA from the same cells and tissues was expressed in oocytes, in all cases tryptophan was transported far less efficiently than leucine. This defect in tryptophan transport is apparently due to aberrant expression of neutral amino acid transporters in general in Xenopus oocytes.

Amylin increases transport of tyrosine and tryptophan into the brain

Injection of amylin (diabetes-associated peptide) into the hypothalamus induces anorexia, increases brain metabolism of dopamine and serotonin and elevates brain level of tryptophan. When male Sprague-Dawley rats were treated with 50 mg/kg l-tryptophan and l-tyrosine ethyl ester 30 min prior to the intrahypothalamic injection of 2 μg amylin, brain tryptophan and tyrosine levels were selectively increased as compared to rats treated with amylin alone. Hypothalamic and striatal serotonin metabolism also appeared to be increased following the amino acid-amylin treatment combination. These results suggest that amylin may increase transport of tyrosine and tryptophan into the brain, and that the increased availability of tryptophan may contribute to increased serotonin turnover observed following intrahypothalamic amylin treatment.

Transport of neurotransmitter precursors in a syncytial epithelium

1. Tegumental transport of choline at concentrations ranging from 0.005–5.0 mM provided no evidence for saturable, carrier-mediated entry of this amine in the tegument of the rat tapeworm ( Hymenolepis diminuta). 2. In contrast, the large neutral amino acid tryptophan appears to be taken up via a high-affinity transporter. In the 1st quartile of 17-day-old tapeworms ( K m = 0.033 mM, V max = 0.7 nmol·min −1 · g −1), in the 2nd quartile ( K m = 0.015 mM, V max = 0.3 nmol·min −1 · g −1), in the 3rd quartile ( K m = 0.022 mM, V max = 0.5 nmol · min −1 · g −1) and in the 4th quartile ( K m = 0.025 mM, V max = 0.5 nmol · min −1 · g −1) saturable tryptophan transport was kinetically characterized. 3. The non-saturable diffusion component (Kd) for tryptophan transport ranged from 3.8–10.2 μl · min −1 · g −1. 4. These studies suggest choline does not appear to be transported across the tapeworm tegument. Saturable transport of tryptophan via a high-affinity carrier is reported, and no regional variations in indole amino acid uptake were detected.