Role of Nuclear Receptors

It has been known since the late 1960s that the amount of bile acid synthesized by the liver is regulated precisely (103, 104). When bile acids accumulate, synthesis is reduced by a negative feedback mechanism that decreases the expression of two enzymes in the biosynthetic pathway, cholesterol 7a-hydrox-ylase (Figure 1, reaction 1) and sterol 12a-hydroxylase (Figure 2, reaction 8). Conversely, cholesterol accumulation induces bile acid synthesis by activating cholesterol 7a-hydroxylase in some...

Flavoprotein Subunit And Formation Of The Covalent Fad Linkage

Although there were indications that SDH was a flavoprotein as far back as 1939, it was 15 years later before direct spectral evidence was obtained that flavin is present in the enzyme reviewed in (77) . It became apparent that SDH contained flavin adenine dinucleotide (FAD) attached to the protein through a covalent flavin linkage (78), the first covalent flavin linkage reported for any protein. A decade later, the covalent flavin was identified as an 8a-V3-histidyl-FAD linkage (79) and the...

Future Outlook And Summary

As noted at the outset of this review, the success of genome sequencing efforts has fueled considerable interest in the area of proteomics, that is, the characterization of the protein complement of a cell or organism. The challenges associated with the acquisition, interrogation, and interpretation of proteomic data are substantial, and a variety of technologies, both experimental and computational, will have to be brought to bear if significant progress is to be made in this endeavor....

J

Cholesterol absorption is reduced to < 5 of normal in the mutant mice, which results in a 200 increase in hepatic cholesterol synthesis. These alterations maintain cholesterol homeostasis (15). About 90 of the cholesterol 7a-hydrox-ylase deficient mice die within the first three weeks of birth. These short-lived mice produce only small amounts of hepatotoxic monohydroxy bile acids (14). Animals that survive this period begin synthesizing normal bile acids. Although the bile acid pool size...

Biological Reactivity Formation And Metabolism Of Epoxides

Aliphatic epoxides are highly reactive molecules with mutagenic and in some cases carcinogenic properties (5). The reactivity of these compounds derives from their electrophilicity and resultant reaction with cellular nucleophiles Figure 1 Enzymatic transformations of aliphatic and aromatic epoxides (a) glutathione conjugation (b) hydration (c) isomerization to an aldehyde (d) isomerization to a ketone and (e) carboxylation to a jS-keto acid. Figure 1 Enzymatic transformations of aliphatic and...

Base Excision Repair DNA Glycosylases

Endonuclease Viii

Inside the cell, DNA is subject to attack by a wide variety of reactive species, including electrophilic oxidants, ionizing radiation, ultraviolet light, methylating agents, and even water (13). Nearly all the resulting adducts interfere with the normal template function of the genome in one way or another, and many give rise to mutations by inducing illegitimate recombination or miscoding during DNA replication (14). All free-standing organisms dedicate a considerable fraction of their genomes...

Why Carboxylation And Why CoM

It is interesting that alkene-oxidizing bacteria have evolved such a unique strategy and selected such an atypical cofactor for the metabolism of epoxyal-kanes formed from alkene epoxidation. Epoxides are readily subject to the more ubiquitous reactions of hydrolysis and glutathione conjugation, and these strategies might be predicted to occur instead of the carboxylation strategy described herein. However, there are a number of features of the epoxide carboxylation reactions that make them...

B12dependent reductive dehalogenases

Classes of Dehalogenases and Their Environmental Role Anaerobic microbes containing B12-dependent reductive dehalogenases play an important role in the detoxification of aromatic and aliphatic chlorinated organ-ics, which include compounds on the EPA priority pollutant list such as chlorinated phenols, chlorinated ethenes, andPCBs (146, 147). Exposure to these compounds induces a host of genes involved in removing the chloride ion. Both aerobic and anaerobic microbes can perform dehalogenation...

Reviews

Models proposed for the flagellar motor are cataloged elsewhere 202, 242 . Other reviews on the structure and function of proton-driven motors are available 211, 243-251 . Also available are reviews on sodium motors 252, 253 and on flagellar genetics and assembly 101, 246, 254 -256 , as well as tutorials on the mathematical treatment of motor models 249, 257 . I thank Lloyd Schoenbach and Linda Turner for help with the figures, and Bob Bourret and Bob Macnab for comments on sections of the...