Liver metabolism processes

Side chain oxidation of alkylbenzenes is important in certain metabolic processes One way m which the body rids itself of foreign substances is by oxidation m the liver to compounds that are more polar and hence more easily excreted m the urine Toluene for example is oxidized to benzoic acid by this process and is eliminated rather readily... 

The kinetic properties of chemical compounds include their absorption and distribution in the body, theit biotransformation to more soluble forms through metabolic processes in the liver and other metabolic organs, and the excretion of the metabolites in the urine, the bile, the exhaled air, and in the saliva. An important issue in toxicokinetics deals with the formation of reactive toxic intermediates during phase I metabolic reactions (see. Section 5.3.3). 

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

During the recovery period from exercise, ATP (newly produced by way of oxidative phosphorylation) is needed to replace the creatine phosphate reserves — a process that may be completed within a few minutes. Next, the lactic acid produced during glycolysis must be metabolized. In the muscle, lactic acid is converted into pyruvic acid, some of which is then used as a substrate in the oxidative phosphorylation pathway to produce ATP. The remainder of the pyruvic acid is converted into glucose in the liver that is then stored in the form of glycogen in the liver and skeletal muscles. These later metabolic processes require several hours for completion. 

In terms of nutrients, the liver is the most important metabolic organ in the body. It receives a large volume of nutrient-rich blood directly from the digestive tract, which provides an abundant amount of substrates for metabolism. Metabolic processes involving carbohydrates include ... 

A high plasma concentration of LDL (usually measured as LDL-cholesterol) is a risk factor for the development of atheroma whereas a high concentration of HDL is an anti-risk factor for cardiovascular disease (CVD). Fundamental discoveries relating to cholesterol metabolism and the importance of the LDL receptor made by Nobel laureates Joseph Goldstein and Michael Brown led to an understanding of the role of LDL in atherosclerosis. The impact of HDL in reducing CVD risk is often explained by the removal of excess cholesterol from tissues and its return to the liver, a process known as reverse cholesterol transport. However, evidence from research by Gillian Cockerill and others shows that HDL has a fundamental anti-inflammatory role to play in cardioprotection. 

The liver is the body s largest organ and is central to metabolic processes. The liver performs a wider range of biochemical functions than any other organ. For this reason, the liver is one of the tissues most commonly used by biochemists studying metabolic pathways and their control mechanisms. For simplicity, the various functions to be described in this chapter have been arranged under a number of subheadings. 

A major function of hGH is the promotion of anabolic activity, that is, bone and tissue growth due to increase in metabolic processes. Other biological effects of hGH are stimulation of protein synthesis, elevation of blood glucose level, and improvement of liver function. 

Drugs absorbed through the gastrointestinal tract pass into the hepatic portal vein, which drains into the liver. The liver metabolizes the drug, which leads to reduction in the availability of the drug for interaction with receptors. This is called first pass metabolism. A schematic representation of the process of drug in the body is given in Fig. 5.7. 

Liver Chemical Processing. For protection from dangerous accumulation of various toxins, the body has evolved methods to eliminate foreign substances. Potentially harmful chemicals can originate from myriad sources including foods, liquids, air, and, of course, medications. The liver s role is to inactivate these chemicals and to convert (metabolize) them to water-soluble forms (i.e., forms that dissolve in water rather than fat), which can more easily be filtered and eliminated by the kidneys. 

Three primary tests are incorporated in the health effects area. The microbial mutagenesis assay is based on the property of selected Salmonella typhimurium mutants to revert from a histidine requiring state to prototrophy due to exposre to various classes of mutagens. The test can detect nanogram quantities of mutagens and has been adapted to mimic some mammalian metabolic processes by the addition of a mammalian liver microsomal fraction. The test is used as a primary screen to determine the mutagenic activity of complex mixtures or component fractions. 

Cyt P450 systems are also involved in many other metabolic processes—e.g., the biosynthesis of steroid hormones (see p. 172), bile acids (see p. 314), and eicosanoids (see p. 390), as well as the formation of unsaturated fatty acids (see p. 409). The liver s reddish-brown color is mainly due to the large amounts of P450 enzymes it contains. 

Each hormone is the center of a hormonal regulation system. Specialized glandular cells synthesize the hormone from precursors, store it in many cases, and release it into the bloodstream when needed (biosynthesis). For transport, the poorly water-soluble lipophilic hormones are bound to plasma proteins known as hormone carriers. To stop the effects of the hormone again, it is inactivated by enzymatic reactions, most of which take place in the liver (metabolism). Finally, the hormone and its metabolites are expelled via the excretory system, usually in the kidney (excretion). All of these processes affect the concentration of the hormone and thus contribute to regulation of the hormonal signal. 

Renal/Hepatic function Impairment Excessive blood levels may result in patients with impaired liver or kidney function, including that caused by immature metabolic processes in the infant. 

Mefabo//sm - The half-life of INH is widely variable and dependent on acetylator status. Isoniazid is primarily acetylated by the liver this process is genetically controlled. Fast acetylators metabolize the drug about 5 to 6 times faster than slow acetylators. Several minor metabolites have been identified, one or more of which may be reactive (monoacetylhydrazine is suspected), and responsible for liver damage. The rate of acetylation does not significantly alter the effectiveness of INH. However, slow acetylation may lead to higher blood levels of the drug, and thus to an increase in toxic reactions. 

Liver slices Easy to prepare Cell-cell contact No use of proteolytic enzymes All cell types present Phase 1 and 11 metabolic processes accessible Require fresh tissue Necrosis of slice centre Long-term culture difficult Quantitative studies variable... 

III.e.3.1. Hepatic disease. The liver, like the gut, has enormous redundancy and up to 80% of the organ can be removed without affecting many of its functions including most of the metabolic processes involved in the metabolism of drugs. 

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