PHYSIOLOGY

Metabolic functions of the Learning objectives

liver
Vikramjit Mitra
Jane Metcalf
Abstract
The liver is one of the most important organs in the body and serves
a variety of important functions including metabolic, vascular, immuno-
logical, secretory and excretory functions. It plays a key role in the carbo-
hydrate, protein and fat metabolism in the human body. In this article, we
outline a brief overview of the metabolic functions.
After reading this article, you should be able to
C outline the metabolic processes involved in carbohydrate
metabolism (including glycogenesis, glycogenolysis and
gluconeogenesis)
C outline the metabolic processes involved in protein metabolism
(including transamination and deamination) and the formation
of urea
C outline the metabolic processes involved in lipid metabolism
(including lipogenesis, fatty acid oxidation and the synthesis of
lipoproteins, phospholipids and cholesterol)
C describe the roles played by the liver: as a store of blood; in the
excretion of waste materials (for example, bilirubin, antibiotics
and drug metabolites); in the secretion of bile.

Keywords Liver; metabolic function

Introduction
The liver is the second-largest organ in the body (after the skin),
representing 1.5e2.5% of the lean body mass. It carries out a wide
variety of functions that can be broadly classified under the following
main categories: vascular functions, immunological functions,
metabolic functions, and secretory and excretory functions. In this
article we give a brief overview of the metabolic functions.
Gluconeogenesis: this is the process by which the liver synthe-
sizes glucose from amino acids and other non-hexose carbohy-
drates to build up glycogen reserves in the body. This process
takes place particularly when the hepatic glycogen reserves are
depleted (for example during starvation).
Protein metabolism (Figure 2)
Amino acids are the building units of protein molecules and
contain an amino group (eNH2) and a carboxyl group (eCOOH).
The amino acids link with each other in chains, forming protein

Metabolic functions of the liver Carbohydrate metabolism in the liver

The major metabolic functions of the liver can be broadly
discussed in three main categories. Glycogen

Carbohydrate metabolism (Figure 1)

Glycogenesis: this is the process by which the liver converts Insulin –
Glycogen Glycogen
excess glucose (entering the circulation after a meal following Insulin + glucagon +
synthase phosphorylase
digestion of complex carbohydrates) into glycogen, the stored catecholamines +
form of carbohydrate in the liver. This process is stimulated by
insulin released from the pancreas during the fed state.
Cell
Glucose-1-phosphate
wall
Glycogenolysis: the liver is involved in the breakdown of
glycogen into glucose molecules that can be transported to other
Glucokinase
tissues for generating energy in the form of adenosine triphos- Blood
Glucose-6-phosphate
phate (ATP) in response to low circulating levels of glucose in the Glucose
Glucose-6-
‘normal’ fasting state. GLUT2
phosphatase
Glucose
Glycolysis transporter
Vikramjit Mitra MBBS MRCP is a Specialist Registrar in Gastroenterology
(ST3) at North Tyneside Hospital, UK. He is currently involved in
a research project on the assessment of clinical teaching. Conflicts of
interest: none declared. Krebs’ cycle

Jane Metcalf MBBS FRCP PhD is a Senior Lecturer in Medical Education at
Newcastle University, UK, and a Consultant Gastroenterologist with an
interest in liver disease at North Tees and Hartlepool NHS Foundation
Trust, UK. Her research interests include primary biliary cirrhosis,
interprofessional education and medical education. Conflicts of
interest: none declared.
Glycogen is synthesized by glycogen synthase stimulated by
insulin. Glycogen is broken down (glycogenolysis) by glycogen
phosphorylase under the influence of glucagon, during stress
by catecholamines, and by lack of insulin.
GLUT2, glucose transporter 2.
Figure 1

ANAESTHESIA AND INTENSIVE CARE MEDICINE 13:2 54 Ó 2012 Published by Elsevier Ltd.
 PHYSIOLOGY
molecules. Amino acids are derived from dietary protein and
muscle protein in the human body. They undergo the following
reactions in the liver.
Transamination: the process by which the amino group of one
amino acid (usually an a-amino acid) is transferred to a reactant
a-keto acid (e.g. a-ketoglutaric acid), resulting in the formation
of an amino acid (e.g. glutamic acid) and an a-keto acid
(from the original amino acid). The process is mediated by
transaminase enzymes present in hepatocytes.
a-Ketoglutaric acid þ amino acid/glutamic acidþ
a-keto acid
Deamination: this process involves the removal of an amino
group from the amino acid (glutamate), ultimately resulting in
the formation of ammonia (NH3). This reaction is catalysed by
the enzyme glutamate dehydrogenase. The rest of the amino acid
(a-ketoglutarate), containing carbon and hydrogen atoms, is
utilized for energy production through conversion into glucose
and lipid molecules (however, this is not part of deamination).
Deamination usually follows transamination.
þ sizes phospholipids and cholesterol in the body, some of which
Glutamate þ NAD þ water/NHþ
4 þ a-ketoglutarate þ
NADH þ Hþ
Urea synthesis: the ammonia generated through the process of
deamination above is toxic to human tissues and is therefore
converted into urea by the hepatocytes through the ornithine
(urea) cycle. The urea is ultimately excreted through the kidneys.
The liver also synthesizes non-essential amino acids (mainly
during the transamination reaction), plasma proteins (e.g.
albumin), several clotting factors (II, V, VII, IX and X) necessary
for blood coagulation and immunoglobulins.
Protein metabolism
Protein intake
Synthesis
Body
Amino acid pool protein
Breakdown
Keto acids Ammonia
Gluconeogenesis Urea
CO2 + H2O
+ energy
Glucose
Figure 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 13:2
Lipid metabolism
Lipogenesis: this is the process by which fatty acids are synthesized
from acetyl coenzyme A (acetyl CoA) molecules derived from the
catabolism of carbohydrates and occasionally of proteins in the fed
state (that are in excess to immediate energy needs of the body).
Fatty acid oxidation: initially triglycerides are hydrolysed into
glycerol and fatty acids. The fatty acids are oxidized into acetyl
CoA, which enters the citric acid cycle, producing ATP, carbon
dioxide and water. The glycerol molecules are converted into
dihydroxyacetone molecules, which may either be converted into
pyruvic acid (then metabolized through the glycolytic pathway
generating ATP molecules) or undergo gluconeogenesis (gener-
ating glucose molecules as before).
Lipoprotein synthesis: in addition, the liver synthesizes lipo-
proteins such as low-density lipoprotein (LDL), very-low-density
lipoprotein (VLDL) and high-density lipoprotein (HDL). These
transport fatty acids, phospholipids and cholesterol in the
circulation to various tissues in the body.
Phospholipid and cholesterol synthesis: the liver also synthe-
are bound to lipoproteins and are available to other tissues of the
body while the rest are excreted through bile as cholesterol or
converted into bile acids.
Vascular functions of the liver
Under normal circumstances, the liver contains 10e15% of the
total blood volume in the body. It can both act as a storehouse of
blood when the peripheral circulation is overloaded and release
blood into the circulation when the body loses blood for any
reason. The liver also synthesizes about 50% of the circulating
lymph in the human body. In addition, the Kupffer cells in the
liver act as macrophages and form part of the phagocytic system in
the body; however, this is an immunological function of the liver.
Secretory and excretory functions of the liver
Secretory function: the liver secretes bile containing bilirubin,
water, bile acids, electrolytes, phospholipids and cholesterol. Bile
acids are important for the digestion and absorption of fat and
fat-soluble vitamins from the small intestine.
Excretory function: the secretion of bile also helps in the excretion
of both endogenous substances (e.g. bilirubin, steroid hormone,
calcium) and exogenous substances (e.g. antibiotics and drug
metabolites). Some of these substances are reabsorbed through the
small bowel wall into the bloodstream (enterohepatic circulation)
and are ultimately excreted through the kidneys. A
FURTHER READING
Alberts B, Bray D, Johnson A, et al. Essential cell biology: an introduction
to the molecular biology of the cell. London: Garland Publishers, 1997.
pp. 79e180.
Champe PC, Harvey RA, Ferrier DR. Biochemistry. In: Lippincott’s Illustrated
Reviews. 3rd edn. Philadelphia: Lippincott, Williams & Wilkins, 2008.
Murray KR, Granner KD, Rodwell VW. Harper’s illustrated biochemistry (LANGE
basic science). 27th edn. New York: McGraw-Hill, 2006. pp. 14e270.
55 Ó 2012 Published by Elsevier Ltd.