Bilirubin and hemolytic anemia | eClinpath
Porphyrin and Heme Synthesis and Bilirubin Metabolism
Bilirubin-Induced Neurologic Damage — Mechanisms …
UDP-glucuronosyltransferases (UGTs) belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds including bilirubin, hormones, various drugs as well as environmental carcinogens. Glucuronidation predominantly serves as a pathway for elimination of the different glucuronidated compounds. Seventeen human UGT transcripts have been identified thus far, and the UGT proteins are differentially expressed in a wide-range of human tissues.
Glucuronidation is a major inactivating pathway for a huge variety of exogenous and endogenous molecules, including drugs, polluants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids.
Bile Acid Synthesis and Utilization
The mechanisms by which the animals sense osmotic stress and launch the osmoregulatory response are quite complex. Both disruption of the cuticle and osmotically induced protein damage are believed to induce osmoprotective gene induction. The genes , and several genes are believed to monitor cuticle integrity and to increase glycerol synthesis in response to osmotic stress (). Genome-wide RNAi screening identified 122 genes that suppress the osmotic stress response under normal conditions. When inactivated by RNAi, they cause expression of and glycerol accumulation, attenuating further hypertonic protein damage (). Defective insulin/IGF signaling also contributes to hypertonic stress resistance by increasing the intracellular level of trehalose and activating genes that protect against, or repair, osmotic stress-induced protein damage ().
The stimulatory effect of signaling on metabolic activity and the metabolic rate studies of ; ; ; ) also argue against a hypometabolic effect induced by food restriction. They studied the oxygen consumption and heat production rates of normally fed controls and worms that were restricted by three dietary restriction (DR) protocols: bacterial dilution in liquid culture, axenic liquid culture and the use of Eat mutants. mutations produce defects in pharyngeal pumping that lead to a reduction in food uptake and concomitant DR phenotypes, including a starved appearance, reduced brood size and extended lifespan. Both proxies of metabolic rate remained unchanged or were elevated in restricted worms. Thus food restriction does not act by lowering the rate of metabolism. At first glance the failure to reduce energy expenditure when food is scarce may seem wasteful. One possible explanation is that there is an increased requirement for synthesis of compounds that are otherwise adequately supplied by food. This is consistent with the lower standing levels of ATP measured in young adult (for about the first 5 days of adulthood) worms grown in axenic culture, which induced the strongest DR phenotype. It is not known if DR animals produce more ROS. DR by all three methods increased SOD and catalase activities, and axenic culture effectively enhanced resistance to thermal and oxidative stress. However, these effects may be part of a complex longevity assurance program that can be induced by a number of unfavorable conditions, including DR, rather than a specific response to increased ROS.
The end products of cholesterol utilization are the bile acids
Mutations that compromise the function of the mitochondrial electron transport chain might be predicted to shorten the lifespan but, remarkably, such mutations frequently confer lifespan extension (). In a systematic RNAi screen for genes conferring longevity, genes related to mitochondrial function were over-represented tenfold (). Long-lived worms, in which mitochondrial function was disturbed by RNAi, displayed low ATP levels and oxygen consumption rates compared to appropriate controls. These metabolic phenotypes confirmed an earlier study in which the function of several subunits of the electron transport chain complexes I, III, IV and V were compromised by RNAi knockdown (). These animals were small and showed slow development and behavior (pharyngeal pumping and defecation). Small size, however, is not a universal hallmark of mitochondrial mutants. Hypometabolic mutants, which contain a defect in an iron-sulphur protein subunit of complex III, were reported to have a normal body size (). Some mitochondrial mutants of the Clock family, such as (a gene involved in ubiquinone synthesis) (; review by ) and (involved in the efficiency and fidelity of mitochondrial protein synthesis), are not hypometabolic (; ). Indeed, in mutants complex I activity remains unaltered (; ; ), although this was challenged by ) who found that complex I activity was decreased by approximately 70% while complex II activity was left intact when compared to wild type.
Apart from direct physiological measurements, Ins/IGF-mutant metabolism was also studied by analyzing transcriptional profiles of metabolism-related genes. ) found that, in mutants, gluconeogenesis, glyoxylate pathway activity and trehalose biosynthesis were upregulated relative to the appropriate controls ( versus adults). These authors found similar qualitative changes in dauer larvae compared to recovered dauer larvae. Unlike dauer stage animals, TCA-cycle and respiratory chain activities were not downregulated in mutants, supporting the physiological data discussed above (). In addition, in part explanation for the high ATP levels found in these mutants, the mitochondrial F1-ATPase inhibitor protein (IF1), which specifically inhibits the ATPase activity of ATP synthase under anoxic conditions, was found to be upregulated in .
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This video describes bilirubin production and excretion.
Under aerobic conditions (), will metabolize energy through the standard metabolic pathways. In glycolysis, a series of enzymatic reactions will convert sugars (typically glucose) to pyruvate. During this process, small amounts of ATP are generated and electron carriers are loaded with electrons (NAD+ is reduced to NADH + H+). Consequently, pyruvate is translocated to the mitochondria, decarboxylated and converted into acetyl-CoA. In this process the first completely oxidized carbon is released as CO2. Acetyl-CoA then enters the tricarboxylic acid (TCA) cycle by condensing with oxaloacetate to form citrate. A series of oxidation reactions then ensue with the result that two carbons are expelled as CO2, (G/A)TP is produced and the electron carriers (NAD+ and FAD+) are reduced. Finally, the cycle is completed when oxaloacetate is formed. The electron carriers that were reduced during glycolysis and the TCA cycle deliver their electrons to O2 (with the formation of water) through a series of electron transport chain redox proteins located in the inner mitochondrial membrane. During electron transfer, some of these redox proteins shuttle protons from the mitochondrial matrix to the intramembrane space of the mitochondria, thereby creating an electrochemical gradient. The potential energy in this gradient is finally used by ATP-synthase (another protein complex in the inner mitochondrial membrane) to drive ATP synthesis.
Bilirubin Synthesis, Transport, and Metabolism by …
Sterol-supplemented chemically defined medium will not sustain nematode population growth unless a heme source is added. Hemin chloride can be used, but various heme proteins have proven more effective (; ). Hemoglobin or myoglobin is most often added (; ; ; ); cytochrome can be used to prepare a medium that is free of precipitate (). lacks orthologs of all 7 enzymes (δ-aminolevulinic acid dehydratase, porphobilinogen deaminase, uroporphyrinogen III synthase, uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, protoporphyrinogen oxidase and ferrochelatase), which are needed to synthesize heme from δ-aminolevulinic acid ().
Effects of protein on bilirubin - Things You Didn't Know
Long-lived insulin/IGF-signaling mutants produce less heat per unit oxygen consumed, resulting in a relatively low calorimetric/respirometric ratio (; ; ). This seems to point to enhanced mitochondrial efficiency (likely due to better coupling of oxygen uptake and ATP synthesis) in the Ins/IGF mutants, which in turn should lead to enhanced ATP synthesis. Indeed, high ATP levels (; ) and mitochondrial ATP production rates () were found in these strains. However, differences in age-dependent ATP and calorimetric/respirometric ratio patterns suggest that the coupling efficiency is probably not the sole determinant of the high ATP levels found in Ins/IGF mutants. Moreover, high ATP is not a prerequisite to long lifespan in (). In contrast to these findings, low metabolic rates for Ins/IGF-mutant strains were reported by ). This discrepancy was possibly based on methodological differences and normalization issues, which were discussed at great length in ) and ). The AMP-activated protein kinase -subunit functions in as an energy sensor that couples lifespan to energy levels and insulin-like signals ().
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