![]() Poor nutritional intake is often seen in cirrhotic patients, especially in patients with alcoholic liver disease, which is a large cause of cirrhosis in the United States and worldwide. Malnutrition is present in almost every patient with alcoholic cirrhosis and is frequent in most other types of cirrhosis. For example, erythrocytes generate a large amount of NADPH through the pentose phosphate pathway to use in the reduction of glutathione.G&H What are the most significant nutritional concerns in patients with cirrhosis?ĬM Patients with cirrhosis frequently have either global malnutrition or alterations in specific aspects of nutritional status, such as micronutrient deficiencies, due to multiple mechanisms, including poor nutritional intake, poor absorption, and increased losses. NADPH reduces glutathione via glutathione reductase, which converts reactive H 2O 2 into H 2O by glutathione peroxidase. While the PPP does involve oxidation of glucose, its primary role is anabolic rather than catabolic, using the energy stored in NADPH to synthesize large, complex molecules from small precursors.Īdditionally, NADPH can be used by cells to prevent oxidative stress. The PPP is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in humans. The ratio of NADPH:NADP + is normally about 100:1 in liver cytosol, making the cytosol a highly-reducing environment. In mammals, the PPP occurs exclusively in the cytoplasm it is found to be most active in the liver, mammary gland, and adrenal cortex. NADPH-utilizing pathways, such as fatty acid synthesis, generate NADP +, which stimulates glucose-6-phosphate dehydrogenase to produce more NADPH. It is allosterically stimulated by NADP +. Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme in this pathway. These compounds are used in a variety of different biological processes including production of nucleotides and nucleic acids (ribose-5-phosphate), as well as synthesis of aromatic amino acids (erythrose-4-phosphate). Ribulose-5-phosphate can alternatively undergo a series of isomerizations as well as transaldolations and transketolations that result in the production of other pentose phosphates including fructose-6-phosphate, erythrose-4-phosphate, and glyceraldehyde-3-phosphate (both intermediates in glycolysis). Depending on the body’s state, ribulose-5-phosphate can reversibly isomerize to ribose-5-phosphate. ![]() The second phase of this pathway is the non-oxidative synthesis of 5-carbon sugars. ![]() Glucose 6-phosphate + 2 NADP ++ H 2O → ribulose-5-phosphate + 2 NADPH + 2 H + + CO 2 It also produces nucleic acids and erythrose-4-phosphate, used in the synthesis of aromatic amino acids. It produces ribulose-5-phosphate, used in the synthesis of nucleotides. It is used in reductive biosynthesis reactions within cells (e.g. The overall reaction for this process is: Figure: Figure 1 The Pentose Phosphate Pathway: The pentose phosphate pathway generates reducing equivalents in the form of NADPH. During this process two molecules of NADP +are reduced to NADPH. The first is the oxidative phase in which glucose-6-phosphate is converted to ribulose-5-phosphate. There are two distinct phases in the pathway: the oxidative phase and the non-oxidative phase. The pentose phosphate pathway (PPP also called the phosphogluconate pathway and the hexose monophosphate shunt) is a process that breaks down glucose-6-phosphate into NADPH and pentoses (5-carbon sugars) for use in downstream biological processes. Outline the two major phases of the pentose phosphate shunt: oxidative and non-oxidative phases.
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