MCAT Biochemistry
The Pentose Phosphate Pathway takes place in the cytosol of mammary glands, liver, adrenal cortex, adipose tissue, and red blood cells. This metabolic pathway is essential for producing ribose-5-phosphate, which is needed to synthesize nucleotides, and NADPH, an energy-carrying molecule vital for various biological processes, including cholesterol and fatty acid synthesis, respiratory burst, regenerating glutathione, and metabolizing large quantities of alcohol and heme.
The Pentose Phosphate Pathway is divided into two phases: oxidative and non-oxidative. The oxidative phase is irreversible, whereas the non-oxidative phase is reversible. Key enzymes and reactions include G6P dehydrogenase, which catalyzes the rate-limiting step converting glucose-6-phosphate (G6P) into 6-phosphogluconate (6PG), producing NADPH. The non-oxidative phase involves phosphopentose isomerase and transketolase, which transform ribulose-5-phosphate into ribose-5-phosphate and eventually generate glyceraldehyde-3-phosphate (G3P) and fructose-6-phosphate (F6P) to enter glycolysis. G6PD deficiency, an X-linked recessive disease, causes hemolytic anemia due to reduced NADPH and glutathione availability during periods of oxidative stress. G6PD deficiency is more common in people of African, Middle Eastern, or Mediterranean descent and provides protection against malaria.
Lesson Outline
<ul> <li>Introduction to Pentose Phosphate Pathway</li> <ul> <li>Location: Cytosol of mammary glands, liver, adrenal cortex, adipose tissue, and red blood cells</li> <li>Connection to nucleotide synthesis and NADPH production</li> </ul> <li>Oxidative Phase</li> <ul> <li>Irreversible reactions</li> <li>Glucose-6-phosphate (G6P) conversion to 6-phosphogluconolactone and eventually to ribulose-5-phosphate</li> <ul> <li>G6P dehydrogenase: rate-limiting step</li> <li>Production of first NADPH</li> <li>6-phosphogluconate dehydrogenase: conversion to ribulose-5-phosphate</li> <li>Production of second NADPH and carbon dioxide</li> </ul> </ul> <li>Non-oxidative Phase</li> <ul> <li>Reversible reactions</li> <li>Phosphopentose isomerase: conversion of ribulose-5-phosphate to ribose-5-phosphate</li> <li>Transketolase: conversion of ribose-5-phosphate to glyceraldehyde-3-phosphate and fructose-6-phosphate</li> <ul> <li>Both intermediates enter glycolysis</li> </ul> </ul> <li>G6PD Deficiency</li> <ul> <li>X-linked recessive metabolic disease</li> <li>Hemolytic anemia during periods of oxidative stress</li> <ul> <li>Decrease in NADPH and low availability of active glutathione</li> </ul> <li>Triggers: infections, inflammatory conditions, fava beans, and certain drugs</li> <li>Peripheral blood smear findings: Heinz bodies and bite cells</li> <li>Hemoglobinuria</li> <li>Prevalence in people of African, Middle Eastern, or Mediterranean descent</li> <li>Protection against malaria</li> </ul> </ul>
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FAQs
The Pentose Phosphate Pathway consists of two main phases: the oxidative phase and the non-oxidative phase. The oxidative phase generates NADPH, which is used in reductive biosynthesis reactions, such as lipid synthesis and detoxification of reactive oxygen species. The non-oxidative phase is responsible for the interconversion of various sugars, such as ribose-5-phosphate, which is necessary for nucleotide synthesis.
G6PD deficiency, an X-linked inherited disorder, affects the glucose-6-phosphate dehydrogenase enzyme, which is crucial for the oxidative phase of the Pentose Phosphate Pathway. This deficiency results in a reduced production of NADPH, which in turn leads to a decreased ability to neutralize reactive oxygen species. Consequently, oxidative stress damages red blood cells, leading to hemolytic anemia. Common manifestations of G6PD deficiency include jaundice, dark urine, fatigue, pallor, and formation of Heinz bodies and bite cells in red blood cells.
NADPH is an essential cofactor generated in the oxidative phase of the Pentose Phosphate Pathway. It serves as a reducing agent that is critical for various cellular processes such as lipid biosynthesis, maintaining the integrity of red blood cells by reducing glutathione, and detoxification of reactive oxygen species. NADPH maintains the cellular redox balance and is essential for the proper functioning of our cells.
Ribose-5-phosphate is produced during the non-oxidative phase of the Pentose Phosphate Pathway through a series of enzyme-catalyzed reactions known as sugar rearrangements. Various enzymes, including transketolase, are involved in these interconversions of sugars. Ribose-5-phosphate is an essential ingredient for the synthesis of nucleotides and nucleic acids, including DNA and RNA, and thus plays a vital role in cellular growth and division.
Heinz bodies are spherical inclusions formed within red blood cells as a result of oxidative stress, which occurs when there is insufficient NADPH production, such as in cases of G6PD deficiency. These inclusions are made of denatured hemoglobin proteins that precipitate due to the inability to neutralize reactive oxygen species effectively. Bite cells are red blood cells with portions removed by phagocytic cells that contain Heinz bodies. These irregularly shaped cells are indicators of red blood cell damage in conditions where the Pentose Phosphate Pathway is hindered, such as G6PD deficiency.
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