Carrier molecules, glucose

The citric acid cycle, a nine-step process, also diverts chemical energy to the production of ATP and the reduction of NAD and FAD. In each step of the citric acid cycle (also known as the Krebs cycle) a glucose metabolite is oxidized while one of the carrier molecules, NAD or FAD, is reduced. Enzymes, nature s chemical catalysts, do a remarkable job of coupling the oxidation and reduction reactions so that energy is transferred with great efficiency. 

Reactions involve several enzymes, which have to follow in sequence for lactic acid and alcohol fermentation. This is known as the glucose catabolism pathway, with emphasis on energetic and energy carrier molecules such as ATP, ADP, NAD+ and NADH. In this pathway the six-carbon substrate yields two three-carbon intermediates, each of which passes through a sequence of reactions to the stable end product of pyruvic acid. 

Certain solutes, eg, glucose, enter cells by facilitated diffusion, along a downhill gradient from high to low concentration. Specific carrier molecules, or transporters, are involved in such processes. 

The lipid bilayer arrangement of the plasma membrane renders it selectively permeable. Uncharged or nonpolar molecules, such as oxygen, carbon dioxide, and fatty acids, are lipid soluble and may permeate through the membrane quite readily. Charged or polar molecules, such as glucose, proteins, and ions, are water soluble and impermeable, unable to cross the membrane unassisted. These substances require protein channels or carrier molecules to enter or leave the cell. 

Glucose and galactose enter the absorptive cells by way of secondary active transport. Cotransport carrier molecules associated with the disaccharidases in the brush border transport the monosaccharide and a Na+ ion from the lumen of the small intestine into the absorptive cell. This process is referred to as "secondary" because the cotransport carriers operate passively and do not require energy. However, they do require a concentration gradient for the transport of Na+ ions into the cell. This gradient is established by the active transport of Na+ ions out of the absorptive cell at the basolateral surface. Fructose enters the absorptive cells by way of facilitated diffusion. All monosaccharide molecules exit the absorptive cells by way of facilitated diffusion and enter the blood capillaries. 

Facilitated diffusion is a mechanism of transmembrane transfer that is carrier mediated but not energy-dependent. The carrier molecule is usually a transmembrane protein, which binds molecules and releases them on the other side of the membrane. It is an important mechanism for endogenous substances, such as glucose. 

Thus, a specific carrier molecule is involved, but the process relies on a concentration gradient, as does passive diffusion. The transport of glucose out of intestinal cells into the bloodstream occurs via facilitated diffusion and uses a uniport. 

Special carrier molecules exist for certain substances that are important for cell function and too large or too insoluble in lipid to diffuse passively through membranes, eg, peptides, amino acids, glucose. These carriers bring about movement by active transport or facilitated diffusion and, unlike passive diffusion, are saturable and inhibitable. Because many drugs are or resemble such naturally occurring peptides, amino acids, or sugars, they can use these carriers to cross membranes. 

It has been well-documented that insulin stimulates glucose transport in adipocytes by increasing the Vmax for the reaction rather than by exerting any dramatic effect on the Km for this process. This action is rapid and reversible and is not due to the biosynthesis of new carrier molecules [28,38]. 

The Krebs cycle completes the disassembly of glucose to six molecules of CO2 by combining the two carbon atoms from acetyl-CoA with oxaloacetate to make citrate this is then successively transformed to release two molecules of CO2 and to regenerate oxaloacetate. This reformation of a carrier molecule in a cyclic manner led Hans Krebs to the concept of a metabolic cycle, he first observed this with the urea cycle (Sec. 14.8). 

In this system, glucose is postulated to form a complex with a carrier molecule at the outer surface of the cell. The sugar-carrier complex passes across the membrane and releases free glucose at the inner surface. The process is reversible. The maximum transport rate, Tmax, is limited by fixed properties of the system such as the total number of carriers and their movement. Below this limit, however, transport will vary with the sugar concentration since this determines the extent of complex formation according to Langmuir adsorption or Michaelis-Menten kinetics. Thus unidirectional transport into the cell can be expressed as follows ... 

In spite of the assumptions that led to its final form, eqn 8.19 describes adequately the passive transport of many nonelectrolytes through membranes of blood cells. In many cases, however, eqn 8.19 imderestimates the flux, which suggests that the membrane is more permeable than expected. However, because the permeability increases only for certain species, we can infer that in these cases, transport is facilitated by carrier molecules. One example is the transporter protein that carries glucose into cells. But we issue a word of caution there is little justification for supposing that D in the membrane is equal to its value in aqueous solution or that k has any particular value, and the conclusion that facilitated transport is involved needs additional evidence before it can be accepted. 

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