Lipids
6.3 Metabolism of lipids
6.3.1 Lipolysis
Phospholipids
Glycerol
Phosphoric acid FA
FA
Figure 6.10 Structure of a phospholipid
6.2.2 Compound lipids
Fatty acids and glycerol thus together make up the simple lipids, in so far as they contain carbon hydrogen and oxygen only. However, if we were to incorporate a phosphate or nitrogen group to the fatty acid, we would no longer have a simple lipid – instead we would have a compound lipid.
This can be seen in Figure 6.10 with thephospho- lipids. Phospholipids contain glycerol, fatty acids and phosphoric acid, and they form an integral part of the plasma membrane.
Other types of compound lipids includelipopro- teins, such as chylomicrons, very low density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
These are in effect lipids such as triglycerides and cholesterol surrounded by protein (see Table 6.1 and Figure 6.11). The greater the lipid content in relation to the protein content, the less dense is the lipoprotein, and so chylomicrons are the least dense and HDLs are the most dense. Furthermore in relation to their size, the less dense lipoprotein molecules (chylomicrons) are larger than the more dense lipoproteins (HDL).
Chylomicrons are formed as a result of the digestion of lipids and are produced by the intestinal cells from the absorbed fatty acids in our food before being synthesized to TAGs, which make up by far the largest constituent.
Chylomicrons are then taken to the liver and to
other tissues, where the triglycerides are broken down bylipoprotein lipase(LPL) in the blood to release the fatty acids and then transported into the cell for storage.
6.2.3 Derived lipids
The final group of lipids are the derived lipids, which include cholesterol and the steroids. From Figure 6.12, you can see that the structure of cholesterol is very similar to the steroid hormones.
In fact, cholesterol is crucial for the synthesis of steroid hormones such as testosterone, pro- gesterone, and oestrogen (the sex hormones). A diet totally lacking in cholesterol would prove problematic for sex hormone production.
Table 6.1 Composition of lipoproteins
Lipoprotein Percentage composition
More dense, more protein
More lipid Protein Triacyl- Cholesterol Cholesterol Phospho- MWt
glycerol ester lipid (×10−6)
Chylomicrons 1–2 85–90 2–3 2–3 6–8 >400
VLDL 8–10 50–55 6–8 14–16 16–20 5–10
LDL 18–22 6–10 8–12 35–45 20–25 2–5
HDL 47–52 3–6 2–4 12–18 25–30 0.2–0.4
Chylomicron VLDL LDL
Protein HDL
Key to molecules:
Lipid scale
mainly triglycerides
mainly choles- terol &
phospho- lipids VLDL
diam – 80 mm d < 1
d = 8 nm d – 1.15
LDL HDL
LIPOPROTEINS
Content Size
Figure 6.11 Some characteristics of lipoproteins backbone to result in the formation of three fatty
acids and a glycerol. The ATGL initiates the cleavage of the first free fatty acid whereas the HSL cleaves the second fatty acid and then the MGL completes the removal of the final fatty acid (see Figure 6.13).
The process of lipolysis takes place in adipose tissue and also in muscles, so be aware that muscle cells do contain triglycerides.
Lipoproteins, such as LDL and VLDL, also contain triglycerides which can undergo lipolysis.
However, in this instance, the triglycerides are broken down by the use of a different enzyme, i.e. LPL. Lipoprotein lipase is released by the endothelial cells in the region of adipose tissue
or muscle to bring about the release of fatty acids and glycerol from lipoproteins and thereby results in the uptake of fatty acids by either adipocytes (after eating) or by muscle cells (during exercise).
Lipolysis occurs during exercise and also some hours (around six hours or more) after a meal when fatty acids are needed as an energy source by var- ious tissues. Lipolysis does not occur within a few hours (1–2 hours) after a meal; particularly if the meal is high in carbohydrates.
The fatty acids and glycerol released by adipose tissue as a result of lipolysis pass out of the adipocyte into the blood. The glycerol is soluble, whereas the fatty acids are bound to
18
19 1 2 3
4 5
6 7 8 9 10
1112 13
14 15
1716
Steroid nucleus
Progesterone O
O
HO
Oestradiol (an oestrogen)
HO
cholesterol
O
HO
OH O
corticosterone
Testosterone O
OH OH
Figure 6.12 Derived lipids: cholesterol and steroid hormones. Note how the steroid hormones are derivatives of cholesterol
TRIACYLGLYCEROL
DIACYLGLYCEROL
MONOACYLGLYCEROL
Glycerol + Fatty Acid ATGL
HSL
MGL
Fatty Acid
Fatty Acid
Figure 6.13 Outline of lipolysis
albuminmolecules in blood. Albumin molecules are proteins and have the capacity to carry up to ten fatty acid molecules each. The amount of fatty acids delivered to muscle from adipose tissue is dependent on the blood flow through the adipose tissue and on the numbers of albumin molecules in the blood. More detail about the regulation of fat metabolism during exercise will be explored in Chapter 7.
Once the fatty acid molecules arrive at the mus- cle cell (carried by albumin), they are transported across the plasma membrane by various fatty acid transporters. These include fatty acid binding protein (FABP), fatty acid transport protein (FATP), and fatty acid translocase (FAT– also known as CD36). The greater the presence of the fatty acid transporters in the membrane, the greater the uptake of fatty acids into the cell.
As with other transporters (which are protein molecules), FABP, FATP, and FAT are inducible by exercise and diet. Endurance-trained athletes up-regulate the amount of fatty acid transporters and hence can take up and utilize greater amounts of fatty acids as an energy source. Likewise, a diet high in fat and low in carbohydrate over an extended period of time also leads to more fatty acid transporters being produced. Figure 6.14 illus- trates fatty acid uptake across a muscle membrane Once inside the cytoplasm of the muscle cell, fatty acids are bound to another fatty acid binding protein (FABPcyt), by which they are
VLDL TG
LPL
LCFA
LCFA LCFA
LCFA
LCFA
ACS Signal transduction LCFA ACS
LCFA
LCFA ACS
CoA ACBP
CoA Fatty Acyl CoA
Esterification acylation CYTOSOL
LBP
CD36 AlbLCFA
AlbLCFA
FABP
pm
CD36
CAPILLARY INTERSTITIAL SPACE
PLASMA MEMBRANE
FABPo FATP
AlbFA CD36
b-oxidation
Figure 6.14 Fatty acid uptake across a muscle cell (adapted from Kiens, 2006) transported to the mitochondria. At the outer
membrane of the mitochondria, the fatty acids are activated by the enzyme ACS and CoA, and thus become ‘activated’ fatty acids. The activated fatty acid is attached to a carnitine molecule by the enzymecarnitine palmitoyl transferase(CPT1).
CPT-1 transports the acylcarnitine molecule across the mitochondrial membrane to the inner surface, whereby CPT-2removes the carnitine and leaves the activated fatty acid in the mitochondrial matrix. The carnitine is then translocated back to the outer membrane, where it can pick up another activated fatty acid. This is sometimes known as the carnitine shuttle (Figure 6.15) Only long chain fatty acids are transported in this manner, as medium and short chain fatty acids are capable of passing directly through the mitochondrial membrane without a transporter.