Hepatocytes

A. Contents include the Golgi complex, rough and smooth endoplasmic reticulum (rER and sER), mitochondria, lysosomes, peroxisomes, lipids, and glycogen.

B. Functions of hepatocytes include the following:

1. Hepatocytes convert ammonium to urea.

2. They form and secrete bile.

3. They conjugate bilirubin.

a. Bilirubin (water-insoluble) is derived from the breakdown of hemoglobin by macrophages and Kupffer cells.

b. Bilirubin is endocytosed by hepatocytes and conjugated to glucuronide by glu-curonyltransferase in the sER to form bilirubin-glucuronide (water soluble), which is secreted into bile canaliculi and excreted in feces.

4. Hepatocytes maintain blood glucose levels by glucose uptake and glycogen synthesis.

5. Hepatocytes degrade glycogen to glucose.

6. They perform gluconeogenesis (conversion of amino acids and lipids into glucose).

7. Hepatocytes maintain blood lipid levels by fatty acid uptake, fatty acid esterifica-tion to triglycerides in the sER, and combination of triglycerides with protein in the Golgi complex to form lipoproteins (Figure 16-1), which include the following:

a. Very-low-density lipoprotein (VLDL) is rich in triacylglycerides and travels to adipose tissue and skeletal muscle, where the triacylglycerides are hy-drolyzed by lipoprotein lipase to fatty acids.

b. Low-density lipoprotein (LDL) is rich in cholesterol and distributes cholesterol to cells throughout the body that have specific LDL receptors (see Chapter 1; VC).

C. High-density lipoprotein (HDL) plays a role in the hydrolysis of triacylglycerides in chylomicrons and VLDL by providing apoprotein C for the activation of lipoprotein lipase.

(1) HDL facilitates the flow of excess plasma triacylglycerides and cholesterol back to the liver; therefore, HDL is called "good" cholesterol.

(2) The enzyme lecithin-cholesterol acyl transferase (LCAT) is associated with HDL and converts cholesterol to cholesterol ester (i.e., cholesterol + a fatty acid).

8. Hepatocytes synthesize cholesterol.

Fatty acids Abumin

Fatty acids Abumin v!7

Density

Triacylglyceride (%)

Cholesterol Free (%) Esters (%)

Chylomicrons*

<0.94

85

2

4

VLDL

0.94-1.006

60

6

16

LDL

1.019-1.063

7

10

40

HDL

1.063-1.21

5

4

15

"See Chapter 14

"See Chapter 14

Ultracentrifugation

Figure 16-1. Characteristics of lipoproteins. Lipoproteins are named based on their molecular weight and density separation by ultracentrifugation. Note that very-low-density lipoprotein (VLDL) composition is 60% triacylglycerides, and low-density lipoprotein (LDL) composition is 50% cholesterol.

9. Hepatocytes synthesize plasma proteins (e.g., albumin, fibrinogen, prothrombin).

10. They perform uptake of immunoglobulin A (IgA) and release of secretory IgA into the bile.

11. They perform uptake and inactivation of hormones, lipid-soluble drugs (e.g., barbiturates), and toxins by enzymes in the sER.

12. Hepatocytes metabolize alcohol by using enzymes within peroxisomes.

13. They perform 25-hydroxylation of vitamin D.

14. They secrete a,-antitrypsin, which is a serum protease inhibitor (a,-antitrypsin deficiency is an autosomal recessive disorder that results in pulmonary emphysema because tissue-destructive proteases are allowed to act in an uncontrolled manner).

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