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· The Citric acid cycle also provides __ for biosynthesis. For example, most of the carbon atoms in __ come from __. Many of the amino acids are derived from __ and __
· Citric acid cycle intermediates must be __if any are __
o The CAC will operate to a reduced extent unless new __is formed, because acetyl CoA cannot enter the cycle unless it __; a minimal level mst be maintained to allow the cycle to function
- intermediates
- porphyrins
- succinyl CoA
- alpha-ketoglutarate and oxaloacetate
- replenished
- drawn off for biosynthesis
- oxaloacetate
- condenses with oxaloacetate
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· How is oxaloacetate replenished?
- o Mammals lack the enzymes for the net conversion of acetyl CoA into oxaloacetate or any other CAC intermediate. Rather, oxaloacetate is formed by the carboxylation of pyruvate, in a reaction catalyzed by the biotin-dependent enzyme pyruvate carboxylase
- § Pyruvate + CO2 + ATP + H20 à oxaloacetate + ADP + Pi + 2 H+
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· __ plays a crucial role in __. It is active only in the presence of __, which signifies __
o If the energy charge is high, oxaloacetate is __. If the energy charge is low, oxaloacetate __
§ The synthesis of oxaloacetate by the carboxylation of pyruvate is an __, a reaction that leads to the net synthesis, or replenishment of pathway components
- Pyruvate carboxylase
- gluconeogenesis
- acetyl CoA
- the need for more oxaloacetate
- converted into glucose
- replenishes the CAC
- anaplerotic reaction
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· __, a neurologic and cardiovascular disorder, is caused by a __
o It is partly ameliorated if the __; some of the thiamine in the husk then leaches into the rice kernel
o The problem is exacerbated if the rice is __, because ony the outer layer contains significant amounts of thiamine
- Beriberi
- dietary deficiency of thiamine
- whole rice grain is soaked in water before milling
- polished
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o Characterized by __ and __
§ Damage to the peripheral nervous system is expressed as __(3)__; the heart may be enlarged and the cardiac output inadequate
- neurologic and cariac symptoms
- pain in the limbs, weakness of the musculature, and distorted skin sensation
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· thiamine is the precursor of the __.
o This cofactor is the prosthetic group of three important enzymes: __(3)__
§ __functions in the pentose phosphate pathway
- cofactor thiamine pyrophosphate
- pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase
- Thransketolase
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o The common feature of enzymatic reactions utilizing TPP is the __
§ In beriberi, the levels of __ and __ in the blood are higher than normal
· The increase in the level of __in the blood is especially pronounced after the ingestion of glucose
- transfer of an activated aldehyde unit
- pyruvate and alpha-ketoglutarate
- pyruvate
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· The nervous system relies on __as its only fuel. The product of glycolysis, __, can enter the CAC only through the __
o With that enzyme deactivated, the NS has no source of fuel; other tissues can use __as a source of fuels for the CAC
- glucose
- pyruvate
- pyruvate dehydrogenase complex
- fats
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· Symptoms similar to those of beriberi appear in organisms exposed to __ or __. Both materials have a high affinity for neighboring __, such as those in the reduced __ of the __
- mercury or arsenite
- sulfhydryls
- dihydrolipoyl groups of the E3 component
- pyruvate dehydrogenase complex
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o The binding of mercury or arsenite to the dihydrolipoyl groups does what?
inhibits the complex and leads to the CNS pathologies
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· Treatment for these poisons is the __
o The reagent-metal complex is excreted in the urine
§ 2,3-dimercaptopropanol was developed for it
administration of sulfydryl reagents with adjacent sulfhydryl groups to compete with the dihydrolipoyl residues for binding with the metal ion
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· The CAC was most likely assembled from preexisting reaction pathways. Many of the intermediates formed in the citric acid cycle are used in __
o Thus, compounds like __ were present early in evolution for biosynthetic purposes
metabolic pathways for amino acids and porphyrins
pyruvate, alpha-ketoglutarate, and oxaloacetate
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§ The __ of these __ is favorable thermodynamically and can be used to drive the synthesis of both acyl CoA derivatives and NADH
· These reactions almost certainly formed the core of processes that preceded the CAC evolutionarily
- oxidative decarboxylation
- alpha-ketoacids
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o Interestingly, __ can be directly converted into __by __ of the respective amino acids by __, another key biosynthetic enzyme
Thus, cycles comprising smaller numbers of intermediates used for a variety of biochemical purposes could have existed before the present form evolved.
alpha-ketoglutarate
oxaloacetate
transamination
aspartate aminotransferase
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