Biochemistry of Specialized Tissues
Aim: Adaptation of tissue cells to suit their function.
The Liver: (The greatest organ in its functional capacity).
Structure: 2 major cell types.
1. Parenchymal cells: 60-80% of liver mass.
Part of liver functional units termed: acini (see diagram)
2. Kupffer cells: ~30% (phagocytic role)
Blood Supply: -Portal vein: 1.51 l/min - carries out “Nutrients”.
- Hepatic artery: 0.4 l/min – oxygen supply.
The portal tract consists of: (1) biliary canaliculus (2) portal vein (3) hepatic artery.
Blood flows from portal veins and hepatic arteries through sinusoids towards hepatic
veins.

Blood in the sinusoids is separated from hepatocytes by kupffer cells and space of
Disse.

Bile canaliculi: grooves in hepatocytes lined by microvilli, into which bile is
secreted
bile ducts (direction of flow opposite blood flow.)
Metabolic Roles of the Liver (Normal Hepatic Function):
1. Carbohydrate Metabolism:
a- Interconversion of monosaccharides: Glucose
Gal
Fructose,
Glucose.
b- Conversion of glucose to pentoses (used in nucleic acids synthesis): The Pentose
Phosphate pathway.
c- Glycosis
d- Gluconeogenesis: hepatic glucose output (maintenance of blood glucose level
between meals) along with:
e- Glycogenolysis: the above two functions can be assessed by measuring blood
glucose level.
f- Lactate Utilization: assessed by measuring blood lactate level.
g- Galactose Metabolism: assessed by galactose elimination capacity.
h- Glycogen synthesis: reducing blood sugar level after a rich CHO meal.
2. Lipid Metabolism:
a. TAG synthesis from glucose, fructose, and certain a.a.s. (esp. low-fat diet/high
intakes of CHO/proteins).
b. Endogenous synthesis of TAG: Excess f. as. in. relation to protein will lead to
fatty liver.
c. Fatty acid synthesis.
d. Cholesterol synthesis and excretion.
e. Lipoprotein metabolism: assessed by serum lipid and lipoprotein levels.
f. Synthesis of ketone bodies: during starvation/uncontrolled D.M.
g. Bile acid synthesis: assessed by serum b.acids, tests for fat malabsorption.
h. 25 – Hydroxylation of Vit. D.: assessed by 25-OH cholecalciferol levels.
3. Protein Metabolism:
a. Plasma protein synthesis (including some coagulation factors but not
immunoglobulins): Albumin, α-/β globulins, fibrinogen and blood clotting
factors: II, VII, IX and X. Assessed by plasma protein concentrations.
b. Special transport proteins: transferrin, ceruloplasmia and transcobalamins.
Protein
Clinical Utility
Albumin
Decreased in chronic liver disease
α1–Antitrypsin
Decrease in α1–antitrypsin deficiency
Ceruloplasmin
Decrease in Wilson’s disease
Coagulation factors
Decrease in chronic liver disease
α –Fetoprotein
Decrease in hepatocellular carcinoma
Haptoglobins
Decrease in hemolysis
Transferrin
Saturated with “iron” in hemochromatosis
c. Urea and Ammonia: Assessed by serum and blood urea and NH4+.
4. Amino Acid Metabolism: (see diagram below)
“A.A Pool”
Extrahepatic tissues: via
hepatic arterial blood
portal venous
blood
Interconversion
(TCA cycle / Transamination)
Heme,
purines,pyrs.,
etc.
plasma
protein
Amino Acids
CO2
Glu
plasma
a.as.
plasma
ASP
urea
NH3
oxoacids
O2
5. Storage: a. Glycogen 0.3% of liver wt. in fasting conditions.
10% of liver wt. after CHO-Rich meal.
Glycogen provides glucose up to 12 hrs. after a meal.
b. General store of protein.
c. Store of blood-clotting factors. e.g. Prothrombin.
d. Vitamins store: A, B12.
e. Iron state: as ferritin in parenchymal cells.
In hemochromatosis excess Fe stored in kuppfer cells as: hemosiderin. These
stores provide supply during nutritional inadequacy and pregnancy.
6. Detoxification and Excretion:
a. Bilirubin metabolism: assessed by serum bilirubin levels, urinary bilirubin
and urabilinogen.
b. Excretion of foreign compounds (xenobiotics): Assessed by:
Bromosulpthalein, indocyanine green, aminopyrine excretion.
7. Hormone Metabolism:
a. Metabolism and excretion of steroid hormones.
b. Metabolism of polypeptide hormones.
In clinical practice, assessment of “Liver Function”: the following tests are
performed: Serum levels of bilirubin, hepatic enzymes and proteins. Other tests
are done occasionally.
* Damage to liver may not affect its activity since the liver has considerable
functional reserve. Therefore, the above tests are insensitive indicators.
8. Digestive Secretions:
- Bile: bile salts aid fat digestion.
- Phosphalipids: aid fat emulsification, HCO3- neutralizes gastric activity.
Types of Bile Acids:
Primary: cholic acid/chenodeoxyxholic acid.
Gly/Taurine
Glyco/Tauro cholic acid/ Glyco/tauro cheno- “Conjugates” deoxycholic acid.
Secondary: Deoxycholic acid (formed by bacterial reduction of cholic acid in the gut).
Gly/Taurine
Glyco/Tauro deoxycholic acid “conjugates”
Enterohepatic Circulation of Bile Acids: (see diagram).
Control of bile acids synthesis: 1. Feedback of bile acids into liver dampens down
their synthesis. 2. Cholesterol synthesis control.
350 mg cholesterol/day
Bile acids
650 mg cholesterol/day
lost in feces
Cholesterol in bile is maintained soluble by bile acids precipitation of cholesterol
causes “gall stone.”
- Detoxification (Metabolites synthesis, processing) and Excretion:
- This occurs via two routes:
(1) Water-soluble compounds are passed out to the blood for excretion by the kidney.
(2) Lipid-soluble/insoluble compounds are excreted through the bile, to the feces.
Formation of Water -Soluble Metabolites:
a. Urea formation
b. Xenobiotics metabolism (detoxification processes):
- Converting a toxic, lipophilic molecules into relatively non-toxic, hydrophilic, more
acidic molecules that can easily be excreted by the kidney. (This determines the life
span and activity of the drug introduced).
* Types of reactions involved in xenobiotics metabolism:
- phase (I) reactions: oxidation, reduction, hydrolysis and methylation.
- phase (II) reaction: Conjugation
followed by: Excretion
see detail of these reactions.