Membrane transport energy production

ALTERNATIVE PRODUCT INHIBITION ABORTIVE COMPLEXES ALTERNATIVE SUBSTRATES COMPETITIVE INHIBITOR ABORTIVE COMPLEXES MAPPING SUBSTRATE INTERACTIONS USING KINETIC DATA MEMBRANE TRANSPORT ENERGY OF ACTIVATION Old... 

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

These organelles are the sites of energy production of aerobic cells and contain the enzymes of the tricarboxylic acid cycle, the respiratory chain, and the fatty acid oxidation system. The mitochondrion is bounded by a pair of specialized membranes that define the separate mitochondrial compartments, the internal matrix space and an intermembrane space. Molecules of 10,000 daltons or less can penetrate the outer membrane, but most of these molecules cannot pass the selectively permeable inner membrane. By a series of infoldings, the internal membrane forms cristae in the matrix space. The components of the respiratory chain and the enzyme complex that makes ATP are embedded in the inner membrane as well as a number of transport proteins that make it selectively permeable to small molecules that are metabolized by the enzymes in the matrix space. Matrix enzymes include those of the tricarboxylic acid cycle, the fatty acid oxidation system, and others. 

Ion transport is also often coupled with cellular energy production and with nutrient and product membrane transport. Aside from Papoutsakis work on the influence of methanol transport on growth of methanol-consuming bacteria, the importance of membrane control of nutrient and product fluxes into the cell has been largely ignored by biochemical engineers [25]. Better methods for measuring the pH and electrical potential differences across cell membranes are needed, as is more careful consideration of membrane-mediated processes in cell kinetics models. 

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. 

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. 

The fact that the mitochondrial inner membrane is virtually impermeable to long-chain fatty acyl-CoA, while the fatty acid oxidative machinery is located inside the mitochondrial matrix, a space enclosed by the inner membrane, might create a serious problem for cellular energy production. The problem is solved by the development of a transmembrane carnitine-dependent transport system for the long-chain acyl residue of acyl-CoA. Catalyzed by carnitine acyltransferase I (CAT-I), which is attached to the inner surface of the mitochondrial outer membrane, fatty acyl-CoA is converted to fatty acyl-carnitine by replacing the CoA residue with carnitine (Figure 3). Fatty acyl-carnitine is transported across the mitochondrial inner membrane in exchange for a molecule of free carnitine by carnitine-acylcarnitine translocase. After arrival in the mitochondrial matrix, fatty acyl-carnitine is converted back to acyl-CoA by carnitine acyltransferase II (CAT-II), an enzyme located on the inner surface of the mitochondrial inner membrane. 

In human mitochondria, more than 600 proteins of 2000 proteins coded by mitochondrial and nuclear genes have been fully identified. These proteins include proteins of different pi, molecular weight, hydrophobicity, and localization, but they are all predominantly from the inner membrane of mitochondria. Many proteins were involved in energy production, signaling, biosynthesis, and ion transport. Similar amounts of proteins have been identified in the mitochondria of rats and mice by proteomic studies. In plants, the mitochondrial proteome of Arabidopsis has been well characterized. 

As discussed in Chapter 2, Section 1.4, uncoupling energy production and respiration is one of the fundamental toxic mechanisms. Weak organic acids or acid phenols can transport H+ ions across the membrane so that energy is wasted as heat, and not used to produce ATP. 

A FIGURE 5-1 Schematic overview of the major components of eukaryotic cell architecture. The plasma membrane (red) defines the exterior of the cell and controls the movement of molecules between the cytosol and the extracellular medium. Different types of organelles and smaller vesicles enclosed within their own distinctive membranes (black) carry out special functions such as gene expression, energy production, membrane synthesis, and intracellular transport. 

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