Functions of the Liver
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The liver has an important role in protein catabolism. The rate of protein turnover in the liver is 10 days, which contrasts sharply with the rate of 180 days for muscle proteins. Amino acid degradation is by transamination, deamination and decarboxylation. Oxidative deamination breaks down surplus amino acids and releases energy. Deamination may be coupled with the transfer of an amino group from one amino acid to another (transamination). These reactions produce acetyl CoA, oxoglutarate, succinyl CoA, oxaloacetate and fumarate, all of which enter the citric acid cycle. Amino acids (such as arginine, histidine, lysine, methionine, threonine, phenylalanine and tryptophan) are degraded mainly in the liver, whereas aspartic acid, glutamic acid, glycine, proline and alanine are metabolized in both hepatic and muscle tissue.
Liver physiology
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
The liver has an important role in protein catabolism. The rate of protein turnover in the liver is 10 days, which contrasts sharply with the rate of 180 days for muscle proteins. Amino acid degradation is by transamination, deamination and decarboxylation. Oxidative deamination breaks down surplus amino acids and releases energy. Deamination may be coupled with the transfer of an amino group from one amino acid to another (transamination). These reactions produce acetyl CoA, oxoglutarate, succinyl CoA, oxaloacetate and fumarate, all of which enter the citric acid cycle. Amino acids (such as arginine, histidine, lysine, methionine, threonine, phenylalanine and tryptophan) are degraded mainly in the liver, whereas aspartic acid, glutamic acid, glycine, proline and alanine are metabolized in both hepatic and muscle tissue.
The Immunoglobulin Variable-Region Gene Repertoire and Its Analysis
Cliburn Chan, Michael G. Hudgens, Shein-Chung Chow in Quantitative Methods for HIV/AIDS Research, 2017
Centroblasts undergo somatic hypermutation (SHM) of their IgVRG, accumulating point mutations at a rate of 10−4–10−3 mutations per nucleotide per cell division (orders of magnitude higher than is observed in typical genome replication) [29–31]. The enzyme activation-induced cytidine deaminase (AID) is responsible for the initial lesions in the DNA, which are followed by error-prone repair by the enzyme polymerase eta (polη). Centroblasts eventually differentiate into centrocytes and migrate to the light zone, where they interact with FDC and T cells and receive signals to survive, divide, or differentiate. Some surviving cells leave the GC as memory B cells, while others return to the dark zone and undergo further rounds of proliferation and mutation. At this stage, B cells may also undergo class switch recombination, which swaps out the constant region genes (IGHC) encoding the Fc portion of the antibody, changing the effector function of the antibody [29,30].
Research on the hepatotoxicity mechanism of citrate-modified silver nanoparticles based on metabolomics and proteomics
Published in Nanotoxicology, 2018
Jiabin Xie, Wenying Dong, Rui Liu, Yuming Wang, Yubo Li
In this study, compared with those of control group, the levels of L-serine dehydratase/L-threonine deaminase and phosphoglycerate mutase were up-regulated, while cysteine dioxygenase, alanine, isoleucine, and methionine were down-regulated. L-threonine deaminase is an enzyme in the liver that is responsible for the conversion of L-threonine to α-ketobutyric acid and ammonia. Because α-ketoester can be converted to isoleucine, L-threonine deaminase plays a key role in the synthesis of branched-chain amino acids (Du et al. 2014). Moreover, serine dehydratase and phosphoglycerate mutase 1 catalyze pyruvate and glycerol ester, respectively, to generate serine, thereby producing isoleucine. Isoleucine is a branched chain amino acid, and the carbon skeleton required for its synthesis is derived from the intermediate products of anaerobic and aerobic sugar metabolism. In this research, under the toxic effects of AgNP-cit, the level of isoleucine were potentially down-regulated by L-serine dehydratase/L-threonine deaminase and phosphoglycerate mutase, which disrupted amino acid metabolism and led to liver damage.
Shaddock (Citrus maxima) peels extract restores cognitive function, cholinergic and purinergic enzyme systems in scopolamine-induced amnesic rats
Published in Drug and Chemical Toxicology, 2022
Ayokunle O. Ademosun, Adeniyi A. Adebayo, Temitope V. Popoola, Ganiyu Oboh
Adenosine deaminase (ADA) catalyzes the irreversible removal of amine group from adenosine to form inosine. In the purinergic system, ADA serves as an important point of regulation of adenosine level, a purine nucleoside that mediates diverse physiological conditions. Adenosine has been reported to play a neuromodulatory role in the CNS in mammals (Burnstock 2006, Burnstock et al.2011). In this study, it was observed that scopolamine administration increased the activity of ADA, and this effect was prevented by treatment with shaddock peels extract or donepezil. An increase in ADA activity increases the hydrolysis of adenosine to inosine. Thus, the effect of scopolamine on this enzyme leads to increased removal of extracellular adenosine decreasing its levels, which may lead to impairment of the adenosinergic neurotransmission. The depletion of extracellular adenosine can disrupt memory formation since adenosine has been reported as an important neuromodulator in synaptic plasticity (Burnstock et al.2011, Costa et al.2015, Akinyemi et al.2017). The decrease in ADA activity observed in the shaddock peel extract-treated group as shown in Figure 5 suggests possible mechanisms governing shaddock peel extract or donepezil action on cognitive function. This inhibitory effect on brain ADA activity would have a direct or indirect influence on the prevention of adenosine degradation in the CNS.
Emerging PEGylated non-biologic drugs
Published in Expert Opinion on Emerging Drugs, 2019
Eun Ji Park, Jiyoung Choi, Kang Choon Lee, Dong Hee Na
Since the first PEGylated enzyme products (PEG-adenosine deaminase; Adagen® and PEG-L-asparaginase; Oncaspar®) appeared on the market in the early 1990s, over 18 PEGylated products have been approved and launched (Table 1) [5,6]. The approved PEGylated products include various classes of drug molecules, such as enzymes (adenosine deaminase, asparaginase, uricase, and phenylalanine ammonia lyase), interferons (interferon α-2a, interferon α-2b, and interferon beta-1a), granulocyte colony-stimulating factors, hormones (epoetin-β), antibody fragments (anti-TNF Fab), coagulation factors, oligonucleotide aptamers, synthetic peptides, and small organic molecules (naloxone). In addition, the application of PEGylation to liposome resulted in the stealth liposome-encapsulated doxorubicin (Doxil®), which is approved in 1995 and used to treat AIDS-related Kaposi sarcoma, breast cancer, ovarian cancer, and other solid tumors [7,8]. These approved drug products have demonstrated the applicability and effectiveness of PEGylation technology.