Resonance Raman spectroscopy of bilirubins: band assignments and application to bilirubin/lipid complexation

Yang, Bijun; Morris, Michael D.; Xie, Meiqiang; Lightner, David A.

doi:10.1021/bi00217a015

Cited by 40 publications

(20 citation statements)

References 29 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Spectroscopic studies have shown that the negatively charged propionate groups of bilirubin form ion pairs with the quaternary ammonium of sphingomyelin (38); hence, we postulate that the activation enthalpy reflects the energy required to disrupt this carboxylate/quaternary ammonium ion interaction (since phosphatidylcholine and sphingomyelin possess an identical head group). In contrast to long-chain fatty acids (32), unconjugated bilirubin traverses hepatocyte plasma membranes at a rate similar to that for phosphatidylcholine vesicles.…”

Section: Discussionmentioning

confidence: 89%

Unconjugated Bilirubin Exhibits Spontaneous Diffusion through Model Lipid Bilayers and Native Hepatocyte Membranes

Zucker

Goessling

Hoppin

1999

Journal of Biological Chemistry

122

View full text Add to dashboard Cite

The liver is responsible for the clearance and metabolism of unconjugated bilirubin, the hydrophobic endproduct of heme catabolism. Although several putative bilirubin transporters have been described, it has been alternatively proposed that bilirubin enters the hepatocyte by passive diffusion through the plasma membrane. In order to elucidate the mechanism of bilirubin uptake, we measured the rate of bilirubin transmembrane diffusion (flip-flop) using stopped-flow fluorescence techniques. Unconjugated bilirubin rapidly diffuses through model phosphatidylcholine vesicles, with a first-order rate constant of 5.3 s ؊1 (t1 ⁄2 ‫؍‬ 130 ms). The flip-flop rate is independent of membrane cholesterol content, phospholipid acyl saturation, and lipid packing, consistent with thermodynamic analyses demonstrating minimal steric constraint to bilirubin transmembrane diffusion. The coincident decrease in pH of the entrapped vesicle volume supports a mechanism whereby the bilirubin molecule crosses the lipid bilayer as the uncharged diacid. Transport of bilirubin by native rat hepatocyte membranes exhibits kinetics comparable with that in model vesicles, suggesting that unconjugated bilirubin crosses cellular membranes by passive diffusion through the hydrophobic lipid core. In contrast, there is no demonstrable flip-flop of bilirubin diglucuronide or bilirubin ditaurate in phospholipid vesicles, yet these compounds rapidly traverse isolated rat hepatocyte membranes, confirming the presence of a facilitated uptake system(s) for hydrophilic bilirubin conjugates.Unconjugated bilirubin is the principal degradation product of heme metabolism. Although the physiologic isomer, bilirubin IX␣, is a dicarboxylic acid, the molecule has minimal aqueous solubility at physiologic pH (1, 2) due to the formation of intramolecular hydrogen bonds (3). For this reason, bilirubin undergoes biotransformation in the liver to more polar conjugates prior to secretion in the bile. However, while unconjugated bilirubin is not hydrophilic, neither can it be characterized as lipophilic (1), since this compound is equally insoluble in apolar solvents (e.g. n-hexane, 1-pentanol). These unique physical-chemical properties have generated controversy regarding the mechanism of bilirubin uptake by the liver. Based on the spontaneous leakage from multilamellar liposomes (4), it has been proposed that bilirubin is able to diffuse through cellular membranes (5, 6). On the other hand, in vivo (7) and whole organ (8, 9) studies indicate that hepatic bilirubin uptake is saturable and occurs against a concentration gradient, findings that support a protein-mediated transport mechanism. To date, four putative bilirubin transporters have been identified in liver cells: BSP/bilirubin-binding protein, organic anion-transporting polypeptide, bilitranslocase, and organic anion-binding protein. Each of these proteins facilitates uptake of the hydrophilic organic anion, sulfobromophthalein (BSP), 1 a process that is competitively inhibited by bilirubin (10, 11).However, des...

show abstract

Section: Discussionmentioning

confidence: 89%

Unconjugated Bilirubin Exhibits Spontaneous Diffusion through Model Lipid Bilayers and Native Hepatocyte Membranes

Zucker

Goessling

Hoppin

1999

Journal of Biological Chemistry

122

View full text Add to dashboard Cite

show abstract

“…Infrared microspectroscopy is increasingly used to examine the local structure of bilirubin in gallstones [l-3], both as a clinical diagnostic and as a probe of the mechanism of gallstone formation. Resonance Raman microspectroscopy has also been proposed as a diagnostic for bilirubin gallstones [4, 51. Resonance Raman spectroscopy has been used to study changes in intramolecular hydrogen bonding in the bilirubin-albumin complex [6] and in bilirubin phospholipid complexes [7]. Even surface-enhanced Raman spectroscopy has been applied to the bilirubin-albumin complex system [8].…”

mentioning

confidence: 99%

Normal coordinate analysis of bilirubin vibrational spectra: Effects of intramolecular hydrogen bonding

Yang¹,

Taylor²,

Morris³

et al. 1993

Spectrochimica Acta Part A: Molecular Spectroscopy

Self Cite

View full text Add to dashboard Cite

Ah&act-Normal coordinate analyses are presented for half-bilirnbin molecules. Calculations for the A-B pyrromethenone include intramolecular hydrogen bonds, while those for the C-D chromophore exclude intramolecular hydrogen bonds. Valence force-held parameters have been optimized to correlate closely with the IR and Raman spectra of the target molecules. The results of the calculations are compared with the spectra of bilirnbin IXa and various model compounds in the solid state and solution.

show abstract

“…11,22,23 On the other hand, two intense bands at 1617 and 1584 cm 2 1 have very similar positions to those of the lactam D and lactam A ring vibrations (C5C and C5O stretches) of bilirubin, an important heme metabolite. 37 The present experiments do not permit us to quantify the production of putative degradation products or discuss their clearance rates. They also do not permit us to assess the contributions of such species to dose-limiting toxicity effects.…”

Section: Resultsmentioning

confidence: 86%

Resonance Raman and UV-Visible Spectroscopic Studies of Water-Soluble Sapphyrin Derivative: Drug Localization in Tumor and Normal Mice Tissues

et al. 2001

View full text Add to dashboard Cite

Resonance Raman (RR) and UV-visible (UV-vis) spectroscopy have been applied to the study of sapphyrin localization in tumor human pancreatic adenocarcinoma-bearing mice. The photosensitizer was subcutaneously injected, and the kinetics of drug biodistribution have been followed in a time scale from 1 to 9 days. RR spectra of tumor and tissue samples and UV-vis absorption spectra of tissue extracts in water/methanol (1:4 v/v) mixture were measured. Spectral data were used to identify the presence and to estimate the relative content of sapphyrin in various tissues at various times after the last injection. Results showed a preferential localization of sapphyrin in tumor tissue. Maximal content of drug in tumor tissue was observed at 6 days after the last injection. Results obtained by RR and UV-vis spectroscopy were in good agreement with each other.

show abstract

Resonance Raman spectroscopy of bilirubins: band assignments and application to bilirubin/lipid complexation

Cited by 40 publications

References 29 publications

Unconjugated Bilirubin Exhibits Spontaneous Diffusion through Model Lipid Bilayers and Native Hepatocyte Membranes

Unconjugated Bilirubin Exhibits Spontaneous Diffusion through Model Lipid Bilayers and Native Hepatocyte Membranes

Normal coordinate analysis of bilirubin vibrational spectra: Effects of intramolecular hydrogen bonding

Resonance Raman and UV-Visible Spectroscopic Studies of Water-Soluble Sapphyrin Derivative: Drug Localization in Tumor and Normal Mice Tissues

Contact Info

Product

Resources

About