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80 Cards in this Set
- Front
- Back
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Which enzyme is need to convert BCAA to BCKA?
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BCAA aminotransferase
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Do muscles have a high concentration of BCKA dehydrogenase? What is the consequence of this?
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a) No… b) after BCAA --> BCKA, the BCKA is sent into the circulation for use by other tissues.
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Besides BCKA, what is the other immediate product of BCAA aminotransferase?
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Glutamate
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What are the 4 possible outcomes for glutamate derived from the BCAA aminotransferase in the muscle?
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1. Transamination with pyruvate to make alanine… 2. Transamination with oxaloacetate to form aspartate, whose amino group can be liberated as ammonia… 3. NH4 can be added to its side chain to form Gln (via glutamine synthase and ATP)… 4. It can be used as a substrate by glutamate dehydrdogenase to yield ammonia (urea cycle)
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What is the take home message of BCAA to the muscles?
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muscles can use BCAA for protein synthesis or transaminate to BCKA… and the glutamate will be used to form Gln or Ala
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What happens to Gln and Ala produced in the muscle as a result of BCAA to BCKA transamination?
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transported out of the muscle
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What stimulates glutamine synthase?
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high [H+] and [glucocoritcoid]
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Where does the second NH4 come from in glutamine synthesis?
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1. From a glutamate molecule itself using glutamate dehydrogenase… 2. From aspartate formed from the oxaloacetate when transaminated by glutamate
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What is another way BCKA can be metabolized in muscle, even though the BCKA dehydrogenase concentrations are low?
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Through anapleurotic rxns: Val and Ile can enter the TCA cycle through Succinyl CoA… they are then converted to pyruvate from malate by decarboxylating malate dehydrogenase.
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What are possible fates of pyruvate?
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alanine or acetyl CoA
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What is the fate of the alanine produced in the muscle through BCAA to BCKA metabolism?
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The glucose-alanine cycle: alanine in the liver can be transaminated to pyruvate, the nitrogen is used either in aspartate (plug into the urea cycle) or glutamate (deaminated by glutamate dehydrogenase)… in either case the nitrogen can enter the urea cycle.
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Which enzyme is need to convert BCAA to BCKA?
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BCAA aminotransferase
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What are the uses of pyruvate as a consequence of BCAA?
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it can support glucogenesis: pyruvate --> oxaloacetate (via pyruvate carboxylase); then oxaloacetate --> PEP (via PEPCK) --> glucogenic pathway… Glucose can be sent back to tissue, which in turn can convert to pyruvate and then back to alanine, then sent back to the liver... thus a cycle.
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Do muscles have a high concentration of BCKA dehydrogenase? What is the consequence of this?
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a) No… b) after BCAA --> BCKA, the BCKA is sent into the circulation for use by other tissues.
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What are two useful purposes of the glucose-alanine cycle?
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1. continuous supply of glucose to tissues… 2. safe transport of nitrogen in the circulation.
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Besides BCKA, what is the other immediate product of BCAA aminotransferase?
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Glutamate
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What is the preferred fuel source for tissue that have a high rate of cell turnover, such as the gut or immune system? Why?
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glutamine… DNA synthesis, where glutamine is the major source for nitrogen
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What are the 4 possible outcomes for glutamate derived from the BCAA aminotransferase in the muscle?
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1. Transamination with pyruvate to make alanine… 2. Transamination with oxaloacetate to form aspartate, whose amino group can be liberated as ammonia… 3. NH4 can be added to its side chain to form Gln (via glutamine synthase and ATP)… 4. It can be used as a substrate by glutamate dehydrdogenase to yield ammonia (urea cycle)
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Where does the gut deliver ammonia? Why is this okay?
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the circulation… (portal circulation) to the liver where it is packaged as urea
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What is the take home message of BCAA to the muscles?
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muscles can use BCAA for protein synthesis or transaminate to BCKA… and the glutamate will be used to form Gln or Ala
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What does the oxidation of glutamine in the intestinal epithelial cell result in?
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glutamate --> citrulline and ornithine + NH+
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What happens to Gln and Ala produced in the muscle as a result of BCAA to BCKA transamination?
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transported out of the muscle
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Describe arginine synthesis by the intestines and the kidneys. (hint: think urea cycles ÷ 2 organs)
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a. glutamine enters gut… b. converted to ornitine (enters mitochondria)… c. converted to citrulline (like the urea cycle)… d) citrulline is exported and enters the kidney… e. citrulline is converted to arginosuccinate by arginosuccinate synthase… f. arginosuccinase converts arginosuccinate to arginine and fumarate... arginine enters circulation.
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What stimulates glutamine synthase?
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high [H+] and [glucocoritcoid]
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What can't the intestinal epithelia make arginine?
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it lacks arginosuccinate synhtase
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Where does the second NH4 come from in glutamine synthesis?
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1. From a glutamate molecule itself using glutamate dehydrogenase… 2. From aspartate formed from the oxaloacetate when transaminated by glutamate
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How do the kidneys use glutamine?
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it uses it as a pH buffer in the urine
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What is another way BCKA can be metabolized in muscle, even though the BCKA dehydrogenase concentrations are low?
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Through anapleurotic rxns: Val and Ile can enter the TCA cycle through Succinyl CoA… they are then converted to pyruvate from malate by decarboxylating malate dehydrogenase.
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What does a decrease in pH produce in the kidneys?
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renal glutamase, which causes the deamidation of glutamine
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What are possible fates of pyruvate?
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alanine or acetyl CoA
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Why is it necessary to maintain a proper pH in the renal tubules?
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membrane transporters wil not function out of their pH range.
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What is the fate of the alanine produced in the muscle through BCAA to BCKA metabolism?
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The glucose-alanine cycle: alanine in the liver can be transaminated to pyruvate, the nitrogen is used either in aspartate (plug into the urea cycle) or glutamate (deaminated by glutamate dehydrogenase)… in either case the nitrogen can enter the urea cycle.
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Can the brain use BCAA? What makes this possible?
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yes, the brain has BCAA transaminase
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What are the uses of pyruvate as a consequence of BCAA?
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it can support glucogenesis: pyruvate --> oxaloacetate (via pyruvate carboxylase); then oxaloacetate --> PEP (via PEPCK) --> glucogenic pathway… Glucose can be sent back to tissue, which in turn can convert to pyruvate and then back to alanine, then sent back to the liver... thus a cycle.
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What uses does the brain have for glutamate (produced from the metabolism of BCAA or glutamine in the circulation)?
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Glutamate can be decarboxylated by neurons (by glutamate decarboxylase) to form GABA (a NT)
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What are two useful purposes of the glucose-alanine cycle?
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1. continuous supply of glucose to tissues… 2. safe transport of nitrogen in the circulation.
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Which organs are similar in their use of BCAA?
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brain and muscle
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What is the preferred fuel source for tissue that have a high rate of cell turnover, such as the gut or immune system? Why?
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glutamine… DNA synthesis, where glutamine is the major source for nitrogen
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Which organs export and which import glutamine?
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import: intestine (cell turnover) /kidney (pH control)… export: brain/muscle
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Where does the gut deliver ammonia? Why is this okay?
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the circulation… (portal circulation) to the liver where it is packaged as urea
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Pernicious Anema Lecture:
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What does the oxidation of glutamine in the intestinal epithelial cell result in?
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glutamate --> citrulline and ornithine + NH+
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What happens after the IF-B12 complex is taken up by receptor mediated tranport in the ileum?
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B12 is release from IF and bound to transcobalamin (TC)
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Describe arginine synthesis by the intestines and the kidneys. (hint: think urea cycles ÷ 2 organs)
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a. glutamine enters gut… b. converted to ornitine (enters mitochondria)… c. converted to citrulline (like the urea cycle)… d) citrulline is exported and enters the kidney… e. citrulline is converted to arginosuccinate by arginosuccinate synthase… f. arginosuccinase converts arginosuccinate to arginine and fumarate... arginine enters circulation.
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What causes the accumulation of dUMP, abberant DNA replication and inaccurate DNA repair?
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insufficient B12 (no recycling of Folate)… megaloblastic anemia may result
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What can't the intestinal epithelia make arginine?
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it lacks arginosuccinate synhtase
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What is the common cause of pernicious anemia?
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vitamin B12 deficiency
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How do the kidneys use glutamine?
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it uses it as a pH buffer in the urine
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What are the histological presentation of pernicious anemia?
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hypersegmented neutrophils, panyctopenia (fewer of all cells), Megaloblastic precursors with large nuclei and increased apoptosis. (larger, yet fewer cells).
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What does a decrease in pH produce in the kidneys?
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renal glutamase, which causes the deamidation of glutamine
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What are the physiologic causes of the inability to absorb B12 in pernicious anemia?
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Atrophic gastric epithelia: loss of parietal cells (produce IF), achlorhydria or hypochlorhydria and minimal IF production.
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Why is it necessary to maintain a proper pH in the renal tubules?
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membrane transporters wil not function out of their pH range.
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Why is it that achlorhydria or hypochlorhydria can cause a deficiency in B12?
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failure to degrade B12 binders in food.
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Can the brain use BCAA? What makes this possible?
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yes, the brain has BCAA transaminase
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What causes atrophic epithelia in pernicious anemia?
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chronic gastritis, which may cause an autoimmune rxn, and/or a breakdown of the gastric barrier to stomach acid.
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In pernicious anemia, what is the target of the autoimmune attack?
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parieta cell proton pumps, or IF itself.
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What uses does the brain have for glutamate (produced from the metabolism of BCAA or glutamine in the circulation)?
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Glutamate can be decarboxylated by neurons (by glutamate decarboxylase) to form GABA (a NT)
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Which organs are similar in their use of BCAA?
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brain and muscle
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What are people with pernicious anemia prone to?
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gastric epithelia may be metaplastic… and thus have a higher rate of cancer.
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Which organs export and which import glutamine?
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import: intestine (cell turnover) /kidney (pH control)… export: brain/muscle
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Name 3 function of B12.
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1. Folate recycle: DNA replication and repair is affected here… 2. Homocysteine conversion to methionine (cardiovascular disease)… 3. Fatty acid metabolism: deficiencies may lead to FA acculmation
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Pernicious Anema Lecture:
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In the stomach, what happens to intrinsically bound B12 in food stuff?
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low pH breaks down food binder on B12, the R-Binder has high affinity to B12.
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What happens after the IF-B12 complex is taken up by receptor mediated tranport in the ileum?
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B12 is release from IF and bound to transcobalamin (TC)
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What happens in the neurtal pH of the duodenum?
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degradation of R-binder and binding of B12 to IF
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What causes the accumulation of dUMP, abberant DNA replication and inaccurate DNA repair?
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insufficient B12 (no recycling of Folate)… megaloblastic anemia may result
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What are the neurological effects of a B12 deficiency
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spinal cord demyelination…loss of axons, numbness, tingling, ataxia, memory loss
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can the neurological effects caused by B12 deficiency be reversed?
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no
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What is the common cause of pernicious anemia?
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vitamin B12 deficiency
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What are the histological presentation of pernicious anemia?
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hypersegmented neutrophils, panyctopenia (fewer of all cells), Megaloblastic precursors with large nuclei and increased apoptosis. (larger, yet fewer cells).
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What are the physiologic causes of the inability to absorb B12 in pernicious anemia?
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Atrophic gastric epithelia: loss of parietal cells (produce IF), achlorhydria or hypochlorhydria and minimal IF production.
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Why is it that achlorhydria or hypochlorhydria can cause a deficiency in B12?
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failure to degrade B12 binders in food.
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What causes atrophic epithelia in pernicious anemia?
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chronic gastritis, which may cause an autoimmune rxn, and/or a breakdown of the gastric barrier to stomach acid.
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In pernicious anemia, what is the target of the autoimmune attack?
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parieta cell proton pumps, or IF itself.
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What are people with pernicious anemia prone to?
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gastric epithelia may be metaplastic… and thus have a higher rate of cancer.
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Name 3 function of B12.
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1. Folate recycle: DNA replication and repair is affected here… 2. Homocysteine conversion to methionine (cardiovascular disease)… 3. Fatty acid metabolism: deficiencies may lead to FA acculmation
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In the stomach, what happens to intrinsically bound B12 in food stuff?
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low pH breaks down food binder on B12, the R-Binder has high affinity to B12.
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What happens in the neurtal pH of the duodenum?
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degradation of R-binder and binding of B12 to IF
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What are the neurological effects of a B12 deficiency
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spinal cord demyelination…loss of axons, numbness, tingling, ataxia, memory loss
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can the neurological effects caused by B12 deficiency be reversed?
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no
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