An individual with chronic hypoglycemia was suspected of having a defect in one of the enzymes unique to gluconeogenesis. To identify the defective enzyme, tissue samples from a normal liver were compared to samples from the patient's liver biopsy, using a biochemical assay that measures glucose production from glycerol or malate.It was found that incubation with glycerol produced normal amounts of glucose in both the control and biopsied liver samples; however, incubation with malate did not lead to glucose production in the liver biopsy, even though it did lead to glucose production in the control liver sample.Based on these observations which of the 4 unique gluconeogenesis enzymes is most likely defective in the individual? Consider each enzyme and explain your choice, including why you ruled out enzymes that you did not choose. To answer this question review how glycerol enters gluconeogenesis (figure 9.48) and how citrate cycle metabolites are transported in and out of the mitochondria (figure 10.39). The breakthrough came in 1917 when the American foodchemist James Currie discovered that large amounts of citricacid in the form of citrate could be isolated from the moldAspergillus niger when it was grown in a medium containingsucrose, salts, and iron. Currie teamed up with the chemicalcompany Pfizer to develop proprietary methods to isolatelarge amounts of citrate from liquid Aspergillus cultures.Using optimized fermentation conditions, which takeadvantage of genetically selected Aspergillus strains, modernbiotechnology methods can efficiently convert sucrose intocitrate over a 10-day period by maintaining a constantbiomass (Figure 10.39). Under these conditions, the fungiare functioning as bioreactors by converting most of thesucrose to citrate, rather than diverting it into metabolicreactions to support cell division, which would ultimatelydecrease citrate yields. These closely guarded fermentationmethods produce nearly 500,000 metric tons of citric acidannually.Relative concentration1.00.502468CitrateBiomassSucrose10Aspergillus fermentation (days)Figure 10.39 Most commercial citric acid is derivedfrom a fermentation process using the mold Aspergillus,which efficiently converts sucrose to citrate, the conjugabase of citric acid. The schematic graph shows therelative conversion of sucrose to citrate by Aspergillusover a 10-day period of fermentation. Notice that citrateproduction continues to rise even after a steady-state levof Aspergillus cell mass (biomass) has been reached. Ethanol:......:Anaerobic metabolismGlycolysisNAD+NADH+ATPGlucoseFermentationPyruvateCitratecycleMitochondriaNADATP+NADHLactatedehydrogenase2 ATP+Lactate28 ATPNADElectron transportNADHH₂OO 2ADP + P;OxidativephosphorylationCO2, H2OAerobic metabolismFigure 9.48 Pyruvate has three metabolic fates, dependion the type of organism and the availability of oxygen.Under aerobic conditions, pyruvate is metabolized in themitochondria to produce CO2 and H₂O. When oxygen islimited, however, pyruvate is converted to lactate orethanol (fermentation). The net 32 ATP shown foroxidative phosphorylation is based on 2 ATP generated ithe cytosol by substrate-level phosphorylation inglycolysis and 30 ATP generated in mitochondria (2 ATIgenerated by substrate-level phosphorylation in the citracycle and 28 by ATP synthase during oxidativephosphorylation).

The observation that glucose production from glycerol is normal in the liver biopsy, but glucose…

An individual with chronic hypoglycemia was suspected of having a defect in one of the enzymes unique to gluconeogenesis. To identify the defective enzyme, tissue samples from a normal liver were compared to samples from the patient's liver biopsy, using a biochemical assay that measures glucose production from glycerol or malate. It was found that incubation with glycerol produced normal amounts of glucose in both the control and biopsied liver samples; however, incubation with malate did not lead to glucose production in the liver biopsy, even though it did lead to glucose production in the control liver sample. Based on these observations which of the 4 unique gluconeogenesis enzymes is most likely defective in the individual?

An individual with chronic hypoglycemia was suspected of having a defect in one of the enzymes unique to gluconeogenesis. To identify the defective enzyme, tissue samples from a normal liver were compared to samples from the patient's liver biopsy, using a biochemical assay that measures glucose production from glycerol or malate. It was found that incubation with glycerol produced normal amounts of glucose in both the control and biopsied liver samples; however, incubation with malate did not lead to glucose production in the liver biopsy, even though it did lead to glucose production in the control liver sample. Based on these observations which of the 4 unique gluconeogenesis enzymes is most likely defective in the individual?

Biomedical Instrumentation Systems

1st Edition

ISBN:9781133478294

Author:Chatterjee

Publisher:Chatterjee

Chapter6: Biomedical Electrodes, Sensors, And Transducers

Section: Chapter Questions

Problem 10Q

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