Page 59 - Control Theory in Biomedical Engineering

46 Control theory in biomedical engineering

as molecular aspects of binding of lipoproteins with specific receptors. How-
ever, this information can be found in a review paper (Afonso et al., 2018).
The scheme shown in Fig. 1 presents six metabolic pathways:
1. Route 1 indicates the pathway of intake of cholesterol together with
food. The maximum amount of cholesterol contained in a daily dose
of food is estimated to be 3g (Sabine, 1977; McNamara, 2000). Follow-
ing intake, the cholesterol with the chyme passes to the small intestine
where it is absorbed into the lymphatic system in the form of chylomi-
crons (CM). These chylomicrons gradually release fatty acids (in the form
of free fatty acids) and become aggregates called remnants (chylomicron
remnants; CR). The remnants get into the bloodstream and are taken up
by specific receptors in the liver (route 2). Regardless of this pathway,
cholesterol is also absorbed together with the circulating bile and is trans-
ported via the portal vein to the liver.
2. Routes 3 and 4 describe the enterohepatic circulation of cholesterol
along with the bile between the liver and intestines. The bile released
from the liver contains up to 8% of cholesterol (Guyton and Hall,
2016), while the bile returning via the portal vein contains an additional
amount of cholesterol derived from the membrane of dead intestinal epi-
thelial cells and a part of the dietary cholesterol. Approximately 500mg
of cholesterol circulates along the selected route (Guyton and Hall,
2016). Furthermore, there is an additional factor binding cholesterol
and bile, cholic acid, which is the main component of the bile. To main-
tain a constant pool, cholic acid is synthesized in the liver from choles-
terol as needed (Guyton and Hall, 2016).
3. De novo synthesis of cholesterol takes place mainly in the liver (route 5)
which is the main site of cholesterol synthesis. The rate of cholesterol
synthesis depends on the amount of cholesterol present in the liver.
The lower the concentration of cholesterol in the liver cells, the faster
the rate of its synthesis (van der Wulp et al., 2013).
4. Cholesterol is released from the liver into the bloodstream in the form of
lipoproteins called VLDL, which are transformed into IDL (route 6) and
ultimately into LDL (route 7). Circulating with blood, LDL is captured
by specific cellular receptors (controlled by the PCSK9 protein), follow-
ing which it becomes one of the membrane components and participates
as a substrate in the synthesis of biologically active derivatives, for exam-
ple, steroid hormones (route 8). LDL is therefore a very important form
of lipoproteins, although it is colloquially associated with “bad
cholesterol.” However, the development of atherosclerosis is closely