LIVER FUNCTION
Contents
OUTLINE THE PROCESSES OF HEME CATABOLISM INCLUDING THE FORMATION OF BILIRUBIN, ITS UPTAKE AND
CONJUGATION IN THE LIVER, EXCRETION IN THE BILE AND FORMATION OF OTHER PIGMENTS IN THE GUT ............. 1
DESCRIBE THE ROLE OF THE LIVER IN THE REGULATION OF BLOOD GLUCOSE CONCENTRATIONS, INCLUDING
SYNTHESIS OF GLYCOGEN AND FATTY ACIDS FROM GLUCOSE, AND THE PROCESSES OF GLYCOGENOLYSIS AND
GLUCONEOGENESIS ................................................................................................................................................... 2
SPECIFY THE ROLE OF THE LIVER IN THE SYNTHESIS AND BREAKDOWN OF THE PLASMA PROTEINS AND THE
SYNTHESIS OF UREA .................................................................................................................................................. 4
UNDERSTAND THE UTILISATION OF FATTY ACIDS BY THE LIVER FOR ITS OWN ENERGY REQUIREMENTS ................ 4
AS SHOWN IN WEEK 9 NOTES, DURING PERIODS OF EXTENSIVE FASTING STATES, FATTY ACIDS ARE THE MAJOR
FUEL FOR THE LIVER. ................................................................................................................................................. 4
REFERENCES.............................................................................................................................................................. 5
OUTLINE THE PROCESSES OF HEME CATABOLISM INCLUDING THE FORMATION OF BILIRUBIN, ITS UPTAKE AND
CONJUGATION IN THE LIVER, EXCRETION IN THE BILE AND FORMATION OF OTHER PIGMENTS IN THE GUT
Proteins that contain Haem (a complex red organic pigment containing iron and other atoms to which oxygen binds)
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Haemoglobin (oxygen transport)
Myoglobin (oxygen storage)
Catalase, peroxidase (enzymes – prosthetic group)
Basic summary:
1. Haemoglobin is broken down into many products, including bilirubin and its derivatives (which are then
components of bile).
2. When red blood cells get old and are destroyed (mainly in the spleen), the heme ring breaks down and the Fe2+
is released – forming BILIVERDIN (a molecule with no iron)
3. Biliverdin changes to UNCONJUGATED (“indirect”) BILIRUBIN (by reduction of its central carbon)
4. As this unconjugated bilirubin is insoluble in water, it has to be carried to the liver by albumin.
5. The liver cells take up the unconjugated bilirubin
6. The liver cells transform it into conjugated (“direct”) bilirubin (by conjugating it with glucuronate). This
resulting molecule is now soluble in water
7. The liver cell releases the conjugated bilirubin into the biliary duct system, which carries it to the small
intestine
8. In the small intestine, the conjugated bilirubin is transformed into UROBILINOGEN, some of which is
excreted and some of which is reabsorbed and carried back to the liver and re-excreted into the bile.
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As urobilinogen is water soluble, it may be excreted in the urine (if blood levels are high enough)
Conjugated bilirubin may also be secreted in the urine (if blood levels are high enough)
Unconjugated bilirubin will not be secreted in the urine because it is insoluble
The dark colour of stool is partly a consequence of the conversion of urobilinogen (colourless) to
stercobilinogen (colourless) to stercobilin (brown) in the intestines
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(From lecture notes)
DESCRIBE THE ROLE OF THE LIVER IN THE REGULATION OF BLOOD GLUCOSE CONCENTRATIONS, INCLUDING
SYNTHESIS OF GLYCOGEN AND FATTY ACIDS FROM GLUCOSE, AND THE PROCESSES OF GLYCOGENOLYSIS AND
GLUCONEOGENESIS
(Refer to Week 9 Los (A matter of opinion) for notes on energy metabolism and details on the role of liver in
regulation of blood glucose concentrations in resting, exercise and fasting states)
Blood Glucose
1. The liver maintains normal blood glucose concentrations through the glucose buffer function.
2. When blood glucose level rise, the liver removes the excess glucose to store it as Glycogen.
3. When blood glucose levels begin to fall, glycogen is converted back to glucose via GLYCOGENOLYSIS
4. When blood glucose levels fall below normal limits, amino acids, lactate and glycerol can be converted into
glucose via GLUCONEOGENESIS
Diagram below
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Fatty Acids
1. Triglycerides are hydrolysed into fatty acids and glycerol
2. Fatty acids undergo β-oxidation to be converted into acetyl-CoA to enter the Krebs Cycle
3. Degradation of acetyl-CoA forms carbon dioxide and hydrogen atoms.
4. Hydrogen is oxidised by the oxidative enzymes in mitochondria to form ATP
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SPECIFY THE ROLE OF THE LIVER IN THE SYNTHESIS AND BREAKDOWN OF THE PLASMA PROTEINS AND THE
SYNTHESIS OF UREA
Protein metabolism
1. Occurs when protein stores of the cell are full
2. Thus, additional amino acids in the body fluids are degraded and used for energy or stored as fat or glycogen
3. The proteins lose an amino group to form ammonia and pyruvate and enter the Krebs cycle to be converted to
energy
4. The toxic ammonia in the blood is converted into UREA by the liver and excreted by the kidneys.
UNDERSTAND THE UTILISATION OF FATTY ACIDS BY THE LIVER FOR ITS OWN ENERGY REQUIREMENTS
As shown in Week 9 notes, during periods of extensive fasting states, fatty acids are the major fuel for the liver.
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REFERENCES
Hansen, B. & Jorde, L. (N.D). USMLE Step 1 Lecture Notes. USA: Kaplan medical.
Gaw, A. Cowan, R et. al (1999). Clinical Biochemistry. UK: Churchill Livingstone.
Goldberg, S. (1999). Clinical Biochemistry made ridiculously simple. USA: MedMaster Inc.
Nelson, D & Cox, M. (2004). Lehninger Principles of Biochemistry (4th Edition). New York: WH Freeman & Co.
Sherwood, L. (2004). Human Physiology: From Cells to Systems (5th Edition). Australia: Thompson.
Lecture notes: Liver as integrator; Fasting and Exercise
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