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Hepcidin, a urinary antimicrobial peptide synthesized in the liver. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. In the cytoplasm, there are also residual bodies containing lipofuscin.
The smooth endoplasmic reticulum is quite abundant, although its size varies with the metabolic activity of the hepatocyte. It is concentrated around glycogen depots. Within a liver lobule, there are morphological differences when comparing peripheral and central hepatocytes, mostly influenced by the blood irrigation features. For example, after digestion, peripheral hepatocytes are the first to store glycogen, but they are the last to mobilize this glycogen when the rest of the body is demanding it.
However, fat storing happens first in the centrally located hepatocytes, which usually have more abundant smooth endoplasmic reticulum. U nlike other epithelial cells, hepatocytes are not attached to a basal membrane. Their basolateral membranes are surrounded by low-density extracellular matrix synthesized by the hepatocytes themselves. It facilitates the diffusion and exchange of molecules with the sinusoids through the space of Disse, or perisinousoidal space, which is the space between the fenestrated endothelium and the hepatocytes.
This extracellular matrix lacks laminin, at least when the hepatocyte is differentiated. However, laminin, type IV collagen and fibronectin are thought to be necessary for a proper hepatocyte differentiation. Hepatocytes are connected between each other by gap junctions, and attached by adherent junctions, desmosomes and tight junctions. H epatocytes are polarized cells, that is, there are differences between the regions facing the bile canaliculi and the regions close to the sinusoids Figure 3.
The polarity is essential for a correct functioning of the hepatocyte, and it is disorganized in many liver pathologies. The apical region is in contact with the bile canaliculi.
As in the apical domain of many epithelial cells, there are tight junctions in the apical domain of hepatocytes, that in this case seal and maintain the integrity of the bile canaliculi.
The apical membrane is folded into microvilli that enormously increase the membrane surface. Removing tight junctions from the apical domains leads to cell polarity disorganization. Hepatocyte polarity and bile canaliculi are established during the embryo development period.
T he functional polarity relies on an unequal distribution of transporters and other membrane molecules between the apical and the baso-lateral plasma membrane domains. The Golgi apparatus, endosomes and cytoskeleton microtubules and actin filaments are responsible for the differential distribution of molecules between the two membrane domains.
There are two main delivering pathways of proteins to the apical domain Figure 5. More rare is a pathway involving the exocytosis of lysosomes, for example cooper transporters are shipped in this way. T he main function of hepatocytes is to metabolize substances coming from digestion. The liver is irrigated by the portal vein that gathered molecules resulting from digestion in the intestine. Hepatocytes are also strongly involved in detoxification of potentially harmful molecules. On the other hand, hepatocytes synthesize bile , which is finally released into the intestine and helps in digestion.
For metabolizing molecules from digestion, hepatocytes are placed in a privileged location within the liver: in contact with sinusoids, which bring digested molecules. Their plasma membranes also form the bile canaliculi that drain the bile from the lobules of the liver. G lucose levels. Hepatocytes fetch glucose molecules coming from digestion and store them as glycogen , which is mobilized when the body needs energy.
Glycogen is commonly found near the endoplasmic reticulum, since the glucosephosphatase enzyme is located in this organelle. Glucosephosphatase catalyzes glucosephosphate, the molecular form of glucose after glycogen catabolism, and produces free glucose, which can exit the hepatocyte and reach the blood stream.
Microvilli are present abundantly on the sinusoidal face and project sparsely into bile canaliculi. Hepatocyte nuclei are distinctly round, with one or two prominent nucleoli. A majority of cells have a single nucleus, but binucleate cells are common. Hepatocytes are exceptionally active in synthesis of protein and lipids for export. As a consequence of these activities, ultrastructural examination of hepatocytes reveals bountiful quantities of both rough and smooth endoplasmic reticulum.
In contrast to most glandular epithelial cells that contain a single Golgi organelle, hepatocytes typically contain many stacks of Golgi membranes.
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