Fatty acids transport into cells

Endurance training also has a noteworthy effect on fat metabolism. In sedentary individuals, especially those who have undergone calorie-restricted diets, adipocytes are resistant to the stimulation by the sympathetic nervous system that accompanies physical exercise. For reasons that are still poorly understood, endurance training results in an increased sensitivity of adipocytes to these hormones. This is an important point, because the amount of fatty acids transported into muscle cells and used to drive muscle contraction is directly related to their concentration in blood. Trained muscle can generate more energy by oxidizing ketone bodies. 

Fatty acid transport proteins (FATPs) are an evolutionary conserved family of integral membrane proteins found at the plasma membrane and on internal membranes. FATPs facilitate the unidirectional uptake and/ or intracellular activation of unesterified long-chain and very long-chain fatty acids (LCFAs) into a variety of lipid-metabolizing cells and tissues. 

Fatty acids Despite the fact that fatty acids are lipid soluble, so that they will diffuse across membranes without a transporter, one is present in the plasma membrane to speed up entry into the cells, so that it is sufficient to meet the demand for fatty acid oxidation. Triacylglycerol transport into cells also depends on the fatty acid transporter. Since it is too large to be transported per se, it is hydrolysed within the lumen of the capillaries in these tissues and the resultant fatty acids are taken up by the local cells via the fatty acid transporter (Chapter 7). Hence the fatty acid transporter molecule is essential for the uptake of triacylglycerol. 

Figure 7.8 Comparison of oxygen transport from lung to a cell and then into a mitochondrion with fatty acid transport from an adipocyte to a cell and then into the mitochondria in various tissues/ organs. Fatty add is transported in blood bound to albumin, oxygen is transported in blood bound to haemoglobin. Fatly add is transported within the cell attached to the fatty acid-binding protein (BP), oxygen is transported within a cell attached to myoglobin (Mb). Alb represents albumin, Hb haemoglobin.

Glucose transport into cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport... 

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mv 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel. 

We now explore the remarkable process by which a long-chain saturated fatty acid is converted into two-carbon units (acetate), which can be oxidized to C02 and H20 via the tricarboxylic acid cycle and the electron-transport chain. Fatty acids that enter cells are activated to their CoA derivatives by the enzyme acyl-CoA ligase and transported into the mitochondria for /3 oxidation as we discuss later in this chapter. 

The answer is c. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) The most likely cause of the symptoms observed is carnitine deficiency. Under normal circumstances, long-chain fatty acids coming into muscle cells are activated as acyl coenzyme A and transported as acyl carnitine across the inner mitochondrial membrane into the matrix. A deficiency in carnitine, which is normally synthesized in the liver, can be genetic but it is also observed in preterm babies with liver problems and dialysis patients. Blockage of the transport of long-chain fatty acids into mitochondria not only deprives the patient of energy production, but also disrupts the structure of the muscle cell with the accumulation of lipid droplets. Oral dietary supplementation usually can effect a cure. Deficiencies in the carnitine acyltransferase enzymes I and II can cause similar symptoms. 

Fatty acids are more efficiently degraded because of increased synthesis of molecules that facilitate fatty acid transport and oxidation. The concentration of citric acid cycle and (3-oxidation enzymes increases, as well as the components of the ETC. In addition, the capacity of the muscle cell to remove fatty acids from blood and to transport them into mitochondria increases. For example, increases in the synthesis of fatty acid transporter proteins and fatty acid-binding proteins, as well as carnitine and carnitine acyltransferase, have been observed. 

Cholesterol travels in the bloodstream via lipoprotein complexes called Chylomicrons, VLDL, IDL, LDL, and HDL. Of the five lipoprotein classes, LDL is by far the richest in cholesterol. Cholesterol in plasma lipoproteins exists both as the free sterol and esterified at its hydroxyl position with a long-chain fatty acid, usually unsaturated (see also Table 18.1). The LDL particle contains a single molecule of apoprotein B-lOO (Mr = 513,000) as its primary protein component. Because cholesterol biosynthesis is confined primarily to the liver with some occurring also in intestine, LDL plays an important role in delivering cholesterol to other tissues. Cholesterol esters are too hydrophobic to traverse cell membranes by themselves and must be transported into cells via specialized LDL receptors. 

Glucose transport into muscle cells can be stimulated during exercise because of the activity of the AMP-activated protein kinase Fatty acid uptake into exercising muscle is dependent on the levels of circulating fatty acids, which are increased by epinephrine release. 

During fasting or in uncontrolled diabetes mellitus, fatty acids enter liver cells and are transported from the cytosol into the mitochondrion (Fig. 33.2). NB The carnitine shuttle is needed to transport fatty acids... 

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