Fatty acids membrane transport

Fig. 1. Relative composition of root microsomal membranes from 24 land races, varieties and breeding lines of rice which differ in their salt resistance. Campesterol, Stigmasterol and Sitosterol as % of total sterols 16 0, 18 1, 18 2 and 18 3 fatty acids as % of total fatty acids Na transport on a relative scale from (1) lowest to (9) highest. Data of D.R. Lachno, T.J. Flowers A.R. Yeo (unpublished).

Dutta-Roy, A.K. (2000) Cellular uptake of long chain fatty acids role of membrane associated fatty acid binding/transport proteins. Cellular and Molecular Life Sciences (in press). 

After release from the adipocyte, the fatty acids are transported in the blood as a complex with albumin, as described above. They are then taken up by cells for oxidation This involves transport through the plasma membrane, the cytosol and finally the inner mitochondrial membrane of the cell for oxidation of the fatty acids within the mitochondria. 

Fatty acids are activated on the outer mitochondrial membrane, whereas they are oxidized in the mitochondrial matrix. A special transport mechanism is needed to carry long-chain acyl CoA molecules across the inner mitochondrial membrane. Activated long-chain fatty acids are transported across the membrane by conjugating them to carnitine, a zwitterionic alcohol. The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine. This reaction is catalyzed by carnitine acyltransferase I (also called carnitine palmitoyl transferase I), which is bound to the outer mitochondrial membrane. 

Compartmentation. The metabolic patterns of eukaryotic cells are markedly affected by the presence of compartments (Figure 30 3). The fates of certain molecules depend on whether they are in the cytosol or in mitochondria, and so their flow across the inner mitochondrial membrane is often regulated. For example, fatty acids are transported into mitochondria for degradation only when energy is required, whereas fatty acids in the cytosol are esterified or exported. 

Certain fatty acids (primarily myristic and palmitic acids) are covalently attached to a wide variety of eukaryotic proteins. Such proteins are referred to as acylated proteins. Fatty acid groups (called acyl groups) clearly facilitate the interactions between membrane proteins and their hydrophobic environment. Fatty acids are transported from fat cells to body cells esterified to serum proteins and enter cells via acyl transfer reactions. Some of the acylated proteins in cells... 

When certain hormones bind to their receptors in adipose tissue, a cascade mechanism releases fatty acids and glycerol from triacylglycerol molecules. Triacylglycerol lipase (sometimes referred to as hormone-sensitive lipase) is activated when it is phosphorylated by protein kinase. Protein kinase is activated by cAMP. After their transport across the plasma membrane, fatty acids are transported in blood to other organs bound to serum albumen. 

Fatty acids are transported between organs either as unesterified fatty acids complexed to serum albumin or in the form of triacylglycerols associated with lipoproteins. Triacylglycerols are hydrolyzed outside cells by lipoprotein lipase to yield free fatty acids (Chapter 19). The mechanism by which fatty acids enter cells remains poorly understood despite a number of studies performed with isolated cells from various tissues [4]. Kinetic evidence has been obtained for both a saturable and a non-saturable uptake of fatty acids. The saturable uptake predominates at nanomolar concentrations of fatty acids and is thought to be mediated, or assisted, by proteins. In contrast, the non-saturable uptake that is effective at higher concentrations of fatty acids has been attributed to passive diffusion of fatty acids across the membrane. Several suspected fatty acid transport proteins have been identified [5]. Although their specific functions in fatty acid uptake remain to be elucidated, these proteins may assist in the desorption of fatty acids from albumin and/or function in uptake coupled to the esterification of fatty acids with CoA, in a process referred to as vectorial acylation. 

LCFA oxidation occurs mairily in mitochondria but rat liver microsomes and peroxisomes contain also both membrane-bound/malonyl-CoA-sensitive and soluble/ malonyl-CoA-insensitive (luminal) CPT-like enzymes. " Thus, a similar fatty acid transport system operates in mitochondria, peroxisomes and microsomes, but it seems that the components involved in these systems are all different. The physiological role of these fatty acid transport systems in microsomes and peroxisomes remains unclear. The microsomal CPTs may have a role in providing fatty acids for transport of proteins through the Golgi apparatus and for acylation of secreted proteins. Since oxidation of very long-chain fatty acids is confined to peroxisomes, a possible role for the peroxisomal CPTs may be to shuttle chain-shorted products out of peroxisomes for further oxidation in mitochondria. 

Clarke, DC Miskovic, D Han, X-X Calles-Escandon, J Glatz, JF Luiken, JJ et al. Overexpression of membrane associated fatty acid binding protein (FABPpm) in vivo increases fatty acid sarcolemmal transport and metabolism. Physiol Genomics, 2004 17(1) 31-7. 

Guillot, A., Obis, D. Mistou, M. Y. (2000). Fatty acid membrane composition and activation of glycine-betaine transport in Lactococcus lactis subjected to osmotic stress. Int. J. Food Microbiol, 55,47-51. 

Phospholipids. Phospholipids, components of every cell membrane, are active determinants of membrane permeabiUty. They are sources of energy, components of certain enzyme systems, and involved in Hpid transport in plasma. Because of their polar nature, phosphoUpids can act as emulsifying agents (42). The stmcture of most phosphoUpids resembles that of triglycerides except that one fatty acid radical has been replaced by a radical derived from phosphoric acid and a nitrogen base, eg, choline or serine. 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

This is a crucial point because (as we will see) proton transport is coupled with ATP synthesis. Oxidation of one FADHg in the electron transport chain results in synthesis of approximately two molecules of ATP, compared with the approximately three ATPs produced by the oxidation of one NADH. Other enzymes can also supply electrons to UQ, including mitochondrial 5w-glyc-erophosphate dehydrogenase, an inner membrane-bound shuttle enzyme, and the fatty acyl-CoA dehydrogenases, three soluble matrix enzymes involved in fatty acid oxidation (Figure 21.7 also see Chapter 24). The path of electrons from succinate to UQ is shown in Figure 21.8. 

All of the other enzymes of the /3-oxidation pathway are located in the mitochondrial matrix. Short-chain fatty acids, as already mentioned, are transported into the matrix as free acids and form the acyl-CoA derivatives there. However, long-chain fatty acyl-CoA derivatives cannot be transported into the matrix directly. These long-chain derivatives must first be converted to acylearnitine derivatives, as shown in Figure 24.9. Carnitine acyltransferase I, located on the outer side of the inner mitochondrial membrane, catalyzes the formation of... 

The acetyl-CoA derived from amino acid degradation is normally insufficient for fatty acid biosynthesis, and the acetyl-CoA produced by pyruvate dehydrogenase and by fatty acid oxidation cannot cross the mitochondrial membrane to participate directly in fatty acid synthesis. Instead, acetyl-CoA is linked with oxaloacetate to form citrate, which is transported from the mitochondrial matrix to the cytosol (Figure 25.1). Here it can be converted back into acetyl-CoA and oxaloacetate by ATP-citrate lyase. In this manner, mitochondrial acetyl-CoA becomes the substrate for cytosolic fatty acid synthesis. (Oxaloacetate returns to the mitochondria in the form of either pyruvate or malate, which is then reconverted to acetyl-CoA and oxaloacetate, respectively.)... 

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. 

Pymvate dehydrogenase is a mitochondrial enzyme, and fatty acid synthesis is a cytosohc pathway, but the mitochondrial membrane is impermeable to acetyl-CoA. Acetyl-CoA is made available in the cytosol from citrate synthesized in the mitochondrion, transported into the cytosol and cleaved in a reaction catalyzed by ATP-citrate lyase. 

---