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71 Cards in this Set
- Front
- Back
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What is the key site (pathway) for NADPH and ribose-5-phosphate synthesis?
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PPP
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Why are reducing equivalents produced in PPP important to RBCs?
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they defend against O2 toxicity
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What is the PPP also referred to as?
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the hexose monophosphate shunt
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Is the PPP unidirectional?
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no, 5 -> 6 and back again
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What other positive aspects are there in th PPP?
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reducing equivalents (NADPH)
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What two things make NADPH production a good thing?
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a) biosynthesis of fatty acids b) prevent oxidative damage
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What role does NADPH drug detoxification?
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NADPH is required in drug detoxification
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Are ingested alternate sugars used in the glycolytic pathways?
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No, they are broken down. If needed they are resynthesized from glucose.
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How can galactose enter the glycolytic pathway?
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converted to glycogen or G-1-P (which can be converted to G-6-P)
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PPP occur in tissue that require high amounts of reducing equivalents (NADPH), which three organs are these?
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liver, mammary glands, the adrenal cortex
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What perctage of glucose oxidation is done by PPP in adipose tissue? Why is this percentage so high?
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a) 50% b) fatty acid biosynthesis occurs there
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What is the first stage of the PPP?
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Oxidative
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Which branch of the PPP produces reducing equivalents?
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the first (oxidative)
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Is the oxidative rxn of the PPP revesible?
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No
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What happens in the first branch of the PPP?
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G-6-P is converted to ribulose-5-phosphate
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What does the non-oxidative branch of the pathway do?
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Converts pentose sugars back into 6 carbon sugars
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Is the non-oxidative branch of the PPP reversible?
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yes
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What is glucose-6-phosphate dehydrognenase? How is it inhibited?
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It converts G-6-P to Ribulose-5-P in the oxidative part of the PPP... b) Feedback (product) Excess NADPH
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What is the branch point for the oxidative part of the PPP?
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G-6-P
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What inhibits oxidative PPP branch?
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product inhibition (NADPH)
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What effect does a high insulin to glucagon ratio have on the oxidative branch of the PPP?
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positive regulation
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What effect does a high insulin to glucagon ratio have on G-6-P dehydrogenase? And it's Vmax?
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a) increases synthesis b) increased Vmax (its capacity)
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Where is the gene for G-6-P dehydrogenase, which plays a key role in PPP?
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X-chromosome
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When would an individual with a defect in G6PD experience difficulty?
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during oxidative stress, since defects in G6PD are sensitive to oxidants
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What is one clinical manifestation of a defect in G6PD?
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hemolytic anemia due to RBC destruction
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Do most mutation in G6PD cause symptoms?
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No
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What is the biochemical reason for the vulnerability of G6PD deficient individuals?
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G6PD (defective) > no NADPH > no reduction of Glutathione thus it cannot cycle between reductase and peroxidase forms > no removal of reactive oxygen species (ROS produced in healthy individuals too), nor hydrogen and lipid peroxides.
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Which form of glutathione deals with radicals?
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glutathione peroxidase
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What food can cause oxidative stress?
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fava beans
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What do oxidants cause?
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crosslinking of hemoglobin, called Heinz bodies, which can cause cell lysing and difficulty passing through capilaries
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Which branch of the PPP is referred to as the transketolase reaction?
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non-oxidative
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What are the 5-carbon sugars converted to in the transketolase reaction?
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F-6-P and Glyceraldehyde-3-P
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What do the transketolase reaction, pyruvate dehydrogenase reaction, and the ∂-ketoglutarate dehydrogenase reactions require?
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Thiamine pyrophosphate as a cofactor
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What is good way to assess a thiamine deficiency?
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check transketolase activity
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What is thiamine deficiency associated with?
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alcohol consumption
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Because thiamine is turned over quickly how do deficiencies present?
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short periods of time over several weeks
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What are the short term symptoms of thiamine deficiency?
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appetite loss, nausea, depression, and fatigue over a short period of time.
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What are the chronic symptoms of thiamine deficiency?
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mental confusion, unsteadiness, loss of eye coordination and congestive heart failure (Wernicke-Korsakoff syndrome)
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Which measurement can be used to diagnose thiamine deficiency?
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Transketolase
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What does a severe deficiency of thiamine cause and what is it known as?
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Beriberi, neuromuscular symptoms, including muscular atrophy and weakness.
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What is the significance of UDP Glucose? How is it formed?
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a) Its an activated sugar with a higher energy level, b) it is formed by the
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What must happen to the glucose prior to conversion to lactose?
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It must first be converted to a higher energy state call UDP-galactose
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Which enzyme converts UDP-glucose to UDP-galactose?
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Epimerase
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What is the linkage configuration of lactose?
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ß-1-4 linkage
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What is the enzyme that converts UDP-galactose to Lactose?
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Lactose synthase (works with ∂-lactalbumin)
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What is alpha lactalbumin?
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a protein that is released after childbirth, in response to prolactin, that modulates the Km by about 1000 times
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In the fructose pathway, what is the first step and which enzyme catatlyzes this step?
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Fructose to F-1-P, fructokinase
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What are the second and third steps in the fructose pathway? And what is the enzyme that catalyzes this process?
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a) F-1-P to dehhydroxyacetone-P to glyceraldehyde-3-P (or vice versa), b) aldolase-B, c) triose kinase
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Which enzyme toggle between dehhydroxyacetone-P and glyceraldehyde-3-P
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triose kinase
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Besides F-1-P, which other substrate can aldolase B (in the liver) metabolize?
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F-1,6-BisP
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Which substrate does aldolase have a lower Km, F-1-P or F-1,6-BisP?
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F-1,6-BisP
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What is the rate limiting step in fructose metabolism?
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F-1-P to dehhydroxyacetone-P or glyceraldehyde-3-P
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In terms of enzymes, why will fructose-1,6-BisP only be metabolized in the liver?
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Aldolase-A, found in the muscle, can only metabolize F-1,6-BisP, while the liver can also metabolize F-1-P
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What are the adverse effects of a fructokinase deficiency?
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none… it's benign… fructose is just excreted
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What are the adverse effects of a deficiency in aldolase B?
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the accumulation of F-1-P inhibits glycogenolysis and gluconeogenesis
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What pH imbalance does the inhibition of gluconeogenesis cause?
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lactic acidosis
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What function does aldolase B serve in Glucose synthesis?
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it synthesizes glucose from G-3-P and DHAP
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What effect does F-1-P have on aldolase, with respect to glucose synthesis
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it depresses aldolase B already low activity
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What effect does the accumulation F-1-P have on cellular phospate?
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it depletes cellular phosphate, due to rapid ATP hydrolysis of fructokinase.
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What effect does low phosphate have on cells?
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low phosphate activate AMP deaminase… amp-> IMP-> uric acid, which leads to depletion of adenine nucleotides… thus ATP synthesis is limited
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What are the two steps in galactose metabolism that leads to the glucose-1-P and ultimately G-6-P? and their enzymes?
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a) Galactose to galactose-1-P (enzyme is galactokinase + ATP) and b) Galactose-1-P to glucose-1-P (enzyme = uridylytransferase also known as GALT)
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In the second step of galactose metabolism how do you derive G-1-P?
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galactose-1-P + UDP glucose -> G-1-P + UDP galactose
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What role does epimerase play?
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UDP galactose -> UDP glucose
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In general which is more serious galactose enzyme deficiencies or frutose deficiencies?
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Galactose, but the scheme is the same, i.e., GALT is worse than galactokinase.
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Which part of galactose metabolism is a deficiency referred to as non-classical? Which is classical?
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a) non-classical deficiency is part one, which involves galacokinase… b) classical deficiency is part two which involves GALT
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How do you treat non-classcal deficency?
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remove galactose and lactose (lactose = glucose and galactose)
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What is a consequence of galactosemia? How does this occur?
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Juvinile cataracts… b) via conversion of galactose to galactitol via aldose reductase in polyol pathway.
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Why does galactitol only occur when galactose is actually ingested?
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Because Km for aldose reductase is high and thus affinity is low, unless galactose is in high quantity.
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What is the problem with the GALT deficiency?
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Galactose-1-P is an inhibitor of UDP-glucose pyrophosphorylase, which is a key enzyme in the breakdown of glycogen
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What are the manifestations of a GALT deficiency?
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failure to thrive, mental retardation, jaundice and liver disease
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How is GALT activity measured?
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blood test
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