The role of liver in metabolism: an updated review with physiological emphasis

Authors

  • Zaenah Zuhair Alamri Department of Biology, Faculty of Science, Jeddah University, Saudi Arabia

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20184211

Keywords:

Bile acids, Circadian, Carbohydrates, Drugs, Liver, Lipids, Metabolism, Proteins, Physiology

Abstract

Liver plays an essential role in metabolism and has an important role in preserving and regulating the levels of lipid, glucose in the body as well as energy metabolism. Among the important functions performed by the liver is maintaining of blood glucose levels under different conditions through group of processes included; glycolysis, glycogenesis, glycogenolysis, gluconeogenesis. The absorbed free fatty acids and those derived from the adipose tissue reach the liver and are utilized for energy, membrane synthesis, or stored as triglyceride. In addition, the liver has a crucial role in keeping homeostasis of body level of cholesterol. Regarding protein metabolism, urea cycle occurs in the liver through the action of urea cycle enzymes to produce urea in order to get rid of the toxic ammonia. In the liver, cholesterol is utilized for bile acids synthesis through a complicated process. These bile acids are considered essential in order to absorb and transport of lipid-soluble vitamins dietary and fat in the diet as well as clearance of drugs, toxic substances and xenobiotics. Adding to these hepatic functions is hepatic detoxification where liver metabolizes a various type of drugs to make soluble execretable compounds. In conclusion, the liver has so important metabolic functions which if impaired will resulted in many liver diseases and might progress to more dangerous conditions such as liver fibrosis or cirrhosis.

References

Mitra V, Metcalf J. Metabolic functions of the liver. Anaesthesia Intensive Care Med. 2009;10(7):334-5.

Vaja R, Ghuman N. Drugs and the liver. Anaesthesia Intensive Care Med. 2017;19(1):30-4.

Chiang J. Liver physiology: Metabolism and detoxification. In: Linda M. McManus, Richard N. Mitchell, editors. Pathobiology of human disease. San Diego: Elsevier. 2014:1770-1782.

Reinke H, Asher G. Circadian clock control of liver metabolic functions. Gastroenterol. 2016 Mar 1;150(3):574-80.

Peek CB, Ramsey KM, Marcheva B, Bass J. Nutrient sensing and the circadian clock. Trends Endocrinol Metab. 2012 Jul 1;23(7):312-8.

Zhang EE, Kay SA. Clocks not winding down: unravelling circadian networks. Nature Rev Mol Cell Biol. 2010 Nov;11(11):764.

Lamia KA, Storch KF, Weitz CJ. Physiological significance of a peripheral tissue circadian clock. Proceed National Academy Sci. 2008 Sep 30;105(39):15172-7.

la Fleur SE, Kalsbeek A, Wortel J, Fekkes ML, Buijs RM. A daily rhythm in glucose tolerance: a role for the suprachiasmatic nucleus. Diabetes. 2001 Jun 1;50(6):1237-43.

Ruiter M, La Fleur SE, van Heijningen C, van der Vliet J, Kalsbeek A, Buijs RM. The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior. Diabetes. 2003 Jul 1;52(7):1709-15.

Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010 Jul;466(7306):627.

Pulimeno P, Mannic T, Sage D, Giovannoni L, Salmon P, Lemeille S, et al. Autonomous and self-sustained circadian oscillators displayed in human islet cells. Diabetol. 2013 Mar 1;56(3):497-507.

Rostom H, Shine B. Basic metabolism: proteins. Surg. 2018;36:4:153-8.

Morris Jr SM. Regulation of enzymes of the urea cycle and arginine metabolism. Ann Rev Nutrition. 2002 Jul;22(1):87-105.

Burgard P, Kölker S, Haege G, Lindner M, Hoffmann GF. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders-review and meta-analysis of observational studies published over more than 35 years. J Inherited Metab Dis. 2016 Mar 1;39(2):219-29.

Morlion BJ, Stehle P, Wachtler P, Siedhoff HP, Köller M, König W, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg. 1998 Feb;227(2):302.

Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Rev Neurosci. 2014 Dec;15(12):771.

Chen CH, Huang MH, Yang JC, Nien CK, Yang CC, Yeh YH, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol. 2006 Sep 1;40(8):745-52.

Shi J, Zhang Y, Gu W, Cui B, Xu M, Yan Q, et al. Serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in Chinese young adults. PloS One. 2012 Nov 7;7(11):e48777.

Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinol. 2000 Sep 1;141(9):3388-96.

Mycielska ME, Patel A, Rizaner N, Mazurek MP, Keun H, Patel A, et al. Citrate transport and metabolism in mammalian cells: prostate epithelial cells and prostate cancer. Bioessays. 2009 Jan;31(1):10-20.

Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Investigation. 2005 May 2;115(5):1343-51.

Tovar‐Méndez A, Miernyk JA, Randall DD. Regulation of pyruvate dehydrogenase complex activity in plant cells. Eur J Biochem. 2003 Mar;270(6):1043-9.

Mashek DG. Hepatic Fatty Acid trafficking: Multiple forks in the road. Adv Nutr. 2013 Nov 6;4(6):697-710.

Erol E, Kumar LS, Cline GW, Shulman GI, Kelly DP, Binas B. Liver fatty acid binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPARα in fasting mice. FASEB J. 2004 Feb;18(2):347-9.

Kamagate A, Qu S, Perdomo G, Su D, Kim DH, Slusher S, et al. FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. J Clin Invest. 2008 Jun 2;118(6):2347-64.

Adamovich Y, Aviram R, Asher G. The emerging roles of lipids in circadian control. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biol Lipids. 2015 Aug 31;1851(8):1017-25.

Le Martelot G, Claudel T, Gatfield D, Schaad O, Kornmann B, Sasso GL, et al. REV-ERBα participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol. 2009 Sep 1;7(9):e1000181.

Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Molecular Cell. 2000 Sep 1;6(3):507-15.

Han S, Zhang R, Jain R, Shi H, Zhang L, Zhou G, et al. Circadian control of bile acid synthesis by a KLF15-Fgf15 axis. Nature Commun. 2015 Jun 4;6:ncomms8231.

Simpson R. Drug therapy in patients with liver disease. In: Brown B, Ed. Anaesthesia for the patient with liver disease. Davis Company. 1981;57e76.

Yang X, Downes M, Ruth TY, Bookout AL, He W, Straume M, et al. Nuclear receptor expression links the circadian clock to metabolism. Cell. 2006 Aug 25;126(4):801-10.

Zhang YK, Yeager RL, Klaassen CD. Circadian expression profiles of drug processing genes and transcription factors in mouse liver. Drug Metab Dispos. 2008 Oct 6; 37:106-15.

Gachon F, Olela FF, Schaad O, Descombes P, Schibler U. The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metabol. 2006 Jul 31;4(1):25-36.

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Published

2018-10-23

How to Cite

Alamri, Z. Z. (2018). The role of liver in metabolism: an updated review with physiological emphasis. International Journal of Basic & Clinical Pharmacology, 7(11), 2271–2276. https://doi.org/10.18203/2319-2003.ijbcp20184211

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Section

Review Articles