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146 Cards in this Set
- Front
- Back
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what is the quintessential coenzyme of aa metabolism
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pyridoxal phosphat (derived from vit B6)
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what is pyridoxal phosphate involved in in aa degradation and synthesis
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removal of amino groups through transamination rxns and donation of amino groups
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what else is pyridoxal phosphate involved in
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rxns that involve carbon skeleton of aas
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what coenzyme is used to transfer one-carbon groups at various oxidation states
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Tetrahyrdofolate (FH4)
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what aas does FH4 help degrade
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serine and histidine
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what aas does FH4 help synthesize
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glycine
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what is the cofactor required for ring hydroxylation rxns…in what aas
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Tetrahydrobiopterin (BH4); phenylalanine to tyrosine
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how many of the 20 common aas can be synthesized in the body
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11-most are aas used for synthesis of additional nitrogen-containing cmpds
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what is glycine used as a substate for
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porphyrin and purine synthesis
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what is glutamate used as a substrate for
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neurotransmitter and purine synthesis
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What is aspartate used a substrate for
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purine and pyrimidine synthesis
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what can 9 of the 11 nonessential aas be synthesized from
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glucose plus a source of nitrogen (like another aa or ammonia)
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what do 2 of the 11 nonessential aas require for synthesis and what are they
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tyrosine and cysteine require another nonessential aa for synthesis (phenylalanine and methionone respectively)
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what 4 aas are produced from glucose via glycolytic pathways components
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serine, glycine, cysteine, and alanine
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what provides components for other 6 glucose dependent nonessential aas
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TCA cycle intermediates
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what is alpha-Ketoglutarate the precursor for
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glutamate, glutamine, proline, and arginine
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what is oxaloacetate the precursor for
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aspartate and asparagine
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what can almost every aa be degraded to when used as a fuel source
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NADH, an electron source for oxidative phosphorylation
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what occurs in the liver during fasting
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aa carbon skeletons produce glucose, ketone bodies, and CO2
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what occurs in liver during fed state
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convert intermediates of aa metabolism to glycogen and triacylglycerols
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when are aas considered glucogenic
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if carbon skeletons can be converted to precursor of glucose
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when are aas considered ketogenic
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if carbon skeletons can be converted directly to acetyl CoA or acetoacetate
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what do aas synthesized from glycilysis intermediates produce when degraded
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pyruvate
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what occurs to aas synthesized by TCA cycle intermediates when degraded
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reconverted back to the same intermediates
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how is histidine degraded
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converted to glutamate then to TCA intermediate alpha-ketoglutarate
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what do methionine, threonone, valine, and isoleucine form when degraded
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succinyl CoA
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What do phenylalanine (thus tyrosine as well) form when degraded
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fumarate
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glucogenic and ketogenic aas that form glucose plus acetyl CoA
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tryptophan, isoleucine, threonine
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glucogenic and ketogenic aas that form glucose plus acetoacetate
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phenylalanine and tyrosine
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what two essential aas are only ketogenic
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lysine and leucine (only produce acetoacetate and acetyl-CoA)
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guthrie bacterial inhibition assay
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spores of Bacillus subtilis plated with B2-thienylalanine (inhibitor of growth); blood sample placed in plate…if phenylalanine >2-4 mg/dL bacterial growth will occur
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3 important cofactors in aa metabolism
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pyridoxal phosphate, tetrahydrofolate (FH4), tetrehydrobiopterin (BH4)
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what is serine synthesized from
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3-phosphoglycerate; serine goes on to produce glycine and cysteine
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what is alanine synthesized from
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transamination of pyruvate
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Step 1 of serine synthesis from glucose
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3-phosphoglycerate is oxidized to a 2-keto cmpd (3-phosphohydroxypyruvate)
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Step 2 of serine synthesis from glucose
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3-phosphohydroxypyruvate is tranaminated to form phosphoserine
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Step 3 in serine synthesis from glucose
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phosphoserine phosphatase removes the phosphate fomring serine
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where are the major sites of synthesis for serine
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liver and kidney
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what is serine generally degraded to by transamination
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hydroxypyruvate, followed by reduction and phosphorylation to form 2-phosphoglycerate (intermediate of glycolysis)
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what can glycine be synthesized from
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serine, minorly threonine
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medically importantt conversion of glycine
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to glyoxylate by enzyme D-amino acid oxidase
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what can occur to glyoxylate once formed
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oxidized to oxalate, which is sparingly soluble and tend to precipitate in kidneys
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what precent of axalate formation in liver comes from glycine metabolism
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40%
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primary oxaluria type 1 (PH 1)
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lack of transaminase that can convert glyoxylate to glycine; causes renal failure
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what does glycine cleavage enzyme create from glycine
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CO2, ammonia, and a carbon that is donated to FH4
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cysteine synthesis
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carbons and nitrogen from serine and sulfur from methionine
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Step 1 of cysteine synthesis
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serine reacts with homocysteine (produced from methionine) to form cystathionine
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what is step 1 of cysteine synthesis catalyzed by
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Beta-synthase
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Step 2 of cysteine sythesis
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cleavage of cystathionine via cystathionase produces cysteine and alpha-ketobutyrate
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what does alpha-ketobutyrate break down into
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succinyl CoA via propionyl CoA
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What do cystathionine B-synthase and cystathionase require
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pyridoxal phosphate (PLP)
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how does cysteine regulate its own production
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inhibits cystathionine B-synthase; helps adjust form dietary cysteine
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when does cysteine become an essential aa
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when methionine supply inadequate; excess dietary custeine 'spares' methionine
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what is cysteine degraded into
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notrogen converted to urea, carbons to pyruvate, sulfur to sulfate
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what are the 2 fates of sulfate
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in aqueous soln, basically makes sulfuric acid; used to generate PAPS
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What is PAPS
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3'-phosphoadenosine 5'-phosphosulfate; used as a sulfate donor in modifying carbs or aas in various structures (like GAGs)
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major degrative route of methionine, homocystein, and cysteine
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methionine to homocysteine to cysteine; only route for homocysteine degradation
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what occurs if there is a vit B6 deficiency or congenital cystathionine B-synthase deficiency
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homocystinemia since homocysteine only has one degradative route; associated with Cardiovascular disease
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what is the medical effect of cystathiouria
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benign disorder; common in remature infants
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cystinuria
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defect in transport protein of intestinal epithelial cells; allows resorption of aas affected by renal cells, but cysteine in not very soluble and forms renal caniculi aka stones
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cystinosis
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defective carrier that normally transports cysteine across lysosomal membrane; forms crystals causing renal failure by6-12 years old
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how is alanine produced
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from pyruvate via transamination rxn catalyzed by alanine aminotransferase (ALT); reversible rxn
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why is alanone the major gluconeogenic aa
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produced in many tissue to transport nitrogen to liver
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how is glutamate formed
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alpha-ketoglutarate via transamination or glutamate dehydrogenase rxn; both reversible
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how can glutamete form glucose in liver
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alpha-ketoglutarate forms malate, which produces glucose via gluconeogenesis
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glutamate is made in synthesizing what other aas
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glutamine, proline, ornithine, and arginine
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what other important molecules does glutamate produce
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glutamyl moiety of glutathione; an important antioxidant
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glutamine formation
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from glutamate by glutamine synthetase-ads NH4+ to carboxyl group of the side chain forming an amide
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what 3 human enzymes can fix free ammonia
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glutamine synthase, glutamate dehydrogenase, and carbamoyl phosphate synthetase I
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what is glutamine reconverted to glutamate by
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glutaminase; important in kidneys-ammonia produced wnters urine and can be used to excrete metabolic aids
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what is the relationship btwn homocysteine and homocystine
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homocystine is 2 homocysteines with a di-sulfide bond
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proline synthesis step 1
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glutamate phosphorylated
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proline synthesis step 2
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converted to glutamate 5-semialdehyde by reduction of the side-chain carboxyl group to an aldehyde
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proline synthesis step 3
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semialdhyde spontaneously cyclizes
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proline synthesis step 4
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cyclic cmpd reduced to form proline
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when is hydroxyproline formed
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when proline is incorporated into collagen by prolyl hydroxylase system
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proline degradation
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converted back to glutamate semialdehyde, which is oxudized to form glutamate; used different ezymes than synthesis
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hydroxyproline degradation
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completely different than proline; aldolase-like rxn occurs once ring hydrolyzed
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arginine synthesis
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glutamate via glutamate semialdehyde transamination to form ornithine
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what is ornithine
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intermediate of urea cycle
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where is ornithine aminotransferase activity the greatest
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small intestine; rxns of urea cycle produce arginine
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when is arginine an essential aa
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during periods of growth when urea cycle argenine synthesis is not sufficient
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what occurs when arginine is used for protein synthesis
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levels of ornithine drops and stimulates formation from glutamate
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how is arginine degraded
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arginase cleaves to form urea and ornithine
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what occurs when ornithineis present in excess for urea cycle requirements
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tansaminated to glutamate semialdehyde and reduced to glutamate; requires PLP
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histidine formation
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is an essential aa
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histimine degradation
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5 of carbons form glutamate
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aspartate producation
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transamination of oxaloacetate; readily reversible
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aparagine formation
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from aspartate in rxn where glutamine provides nitrogen for amide
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asparaginase fxn
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hydrolyzes asparagine to NH4+ and aspartate
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major route for asparatate degradation
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oxaloacetate; although carbons can form furmarate in urea cycle
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process of minor route of asparatae degradation
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reacts with inosine monophosphate (IMP) to form adenylosuccinate intermediate which is cleaved to form AMP and fumarate
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phenylalanine degradation
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converted to tyrosine by hydroxylation rxn; tyrosine is oxidized and forms acetoacetate and fumartate
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These amino acids degrade to form what: methionine, valine, isoleucone, and threonine
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propionyl CoA then succinyl CoA
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where else is propionyl CoA produced
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oxidation of odd-chain fatty acids
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Leukemic cells and many tumor cells require what aa for their growth
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asparagine; asparaginase has been used as anti-tumor agent
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what occurs to propionyl CoA once formed
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carboxylated and forms D-methylmalonyl CoA (requires biotin); this is racemized to L-methylmalonyl CoA
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what does the reation leading to succinyl CoA from propionyl CoA require
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vit B12
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methionine degradation
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converted to S-adenosylmethionine (SAM) which donates its methyl to other cmpds to form D-adenosylhomocysteine (SAH)
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What happens to SAH
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converted to homocysteine
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how can methionine be regenerated
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FH4 plus homocysteine plus B12
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what are carbons of homocysteine metabolized to
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alpha-ketobutyrate, which undergoes oxidative decarboxylation to propionyl CoA
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homocystinuria is caused by…
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enzyme cytathionase B-synthase and cystathionase deficiencies as well as methyltetrahydrofolate (Ch3-FH4) or methyl-B12
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how can you get deficiencies in Ch3-FH4 or methyl-B12
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inadequate dietary intake or defective enzymes that join methyl groups to FH4
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threonine degradation
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PLP-requiring dehydratase to ammonia and alpha-ketobutyrate
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Which aa are universal fuels
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valine, isoleucine, and leucine; all are branched-chain aas
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what carries out branched chain aa oxidation
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mitochondria of most tissues; muscle has highest level
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what aa content in a protein consist of branched-chain aas
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25%
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two fxns of valine and isoleucine degradation
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fuel and provide intermediates for TCA
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first step in branched chain aa degradation
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transamination; remaining steps analagous to B-oxidation of fatty acids-NADH and FAD2H generated
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what do valine and isoleucine convert to when degraded
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succinyl CoA; isoleucine also forms acetyl CoA
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What does leucine form when degraded
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acetoacetate and acetyl CoA-strongly ketogenic
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what is wrong in maple syrup urine disease
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branch-chain alpha-keto acid dehydrogenaase is defective; leads to neuro complications
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what is difficult in treating maple syrup urine disease
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involves 3 amino-acids, so difficult to use dietary constrictions
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alcaptonuria
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homogentisate can't be further oxidized since homogenitsate defective (intermediate in tyrosine metabolism)
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what converts phenylalanine to tyrosine
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hydrolated by phenylalanine hydroxylase (PAH)-requires O2 and tetrahydrobiopterin
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what is tetrahydrobiopterin converted to in the rxn
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quininoid dihydrobiopterin, which must be reconverted in order for rxm to continue producing tyrosine
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tryptophan is oxidized to form…
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alanine, formate, and acetyl CoA
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what can be produced from the ring stucture of tryptophan sparing niacin
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NAD and NADP
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what conditions can cause tyrosinemia
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prematurity, enzyme defects
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tyrosinemia II
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defect in tyrosine aminotransferase (TAT) and may lead to lesion of eye and skin as well as neuro problems
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Tyrosinemia I (aka tyrosinosis)
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defect in fumarylace-toacetate hydrolase; acute form associated with liver failure, cabbagelike body odor, and death within 1st year
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diseases caused by deficiencies in phenylalanine-tyrosine conversion
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PKU, tyrosenemia, alcaptonuria
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what occurs with defect in dihydropteridine reductase (DHPR-required for BH4 regeneration)
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hyperphenylalaninemia which responds to diet change, but symptoms persist and patients die within first 2 years
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what is BH4
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a cofactor of PAH
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what occurs with BH4 defect
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diet control lowers phenylalanine, but BH4 is required for synthesis of neurotransmitters
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what neurotransmitter is BH4 required for
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tryptophan to 5-hydroxytryptophan and tyrosine to L-dopa
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when does pellagra occur
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insufficiency of niacin and tryptophan
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What does pellagra cause
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dermatitis, diarrhea, dementia, finally death
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what occurs in tryptophan degradation if vit B6 is deficient
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enters minor pathway creating xanthurenic acid
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lysine degradation
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can't be directly transaminated at either of its amino groups and is degraded by a complex pathway
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intermediates of lysine degradation
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saccharopine, alpha-ketoadipate, crotonyl CoA; NADH and FADH2 generated in process; ultimately produces acetyl CoA-strictly ketogenic
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indidence of PKU
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100 per million births with wide geographic/ethnic variation
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cause of PKU
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defective PAH gene
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what causes symptoms of PKU
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competative interaction of phenylalanine with brain aa transport systems and inhibition of neurotransmitter synthesis; lead to impaired myelin synthesis and delayed neuro development
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what accumulates in cystathionine B-synthase deficiency
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homocysteine and methionine in the blood
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what pathological effect of the eyes occur in cystathionine B-synthase deficiency
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zzonular fibers that normally hold the lens of the ye become frayed and break causing dislocation of the lens
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what pathological effect of the bones occur in cystathionine B-synthase deficiency
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skeleton has loss of ground substance (may explain curvature of spine often seen); long bones are also elongated leading to tall stature
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what do animal experiements of increased homocysteine and methionine in the brain reveal
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may trap S-adenosylhomocysteine diminishing adenosine levels; adenosine normally acts as a CNS depressant
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why may methionine not appear in urine despite elevated levels
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renal tubular reabsoption of methionine is highly efficient
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why is homocysteine found in urine when elevated
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less efficiently reabsorbed and excess of 1 mmol/day may be excreted
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type II homocystinuria
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defect in synthesis of methyl cobalamin; required for methylation of homocysteine to form methionine
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type III homocystinuria
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defect in synthesis of N5-methyltetrahydrofolate; required for methylation of homocysteine to form methionine
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type I homocystinuria
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cystathionine B-synthase deficiency; homocysteine and methionine levels elevated
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what is associated with elevated homocysteine levels, but there is no known mechanism
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increased thrombi and emboli
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what therapies are in place for homocystinurias
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diet control of homocysteine and methionine; high oral doses of pyridoxine (vit B6)-50% of type 1 respond to
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