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68 Cards in this Set
- Front
- Back
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What can CO2 be transferred by
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biotin
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Carbon in lower levels of oxidation than CO2 can be transferred by
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tetrahydrofolate (FH4) aka vit B12 and S-adenosylmethionine (SAM)
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what is FH4 produced from
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vitamin folate
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what is the primary 1-carbon carrier in the body
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FH4
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where does FH4 obtain 1-carbon units
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serine, glycine, histidine, formaldehyde, and formate
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how can folate exist in several different forms
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the 1-carbon unit can be oxidized or reduced
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can a carbon reduced to methyl-FH4 be reoxidized
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no
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what is the term 'folate' used for
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water-soluble B-complex vitamin that fxns in transferring single-carbon groups at various stages of oxidation
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examples of uses of 1-carbon group pool
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dUMP to dTMP, glycine to serine, precursers of purine bases, and vit B12
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What 2 rxns is vit B12 involved in
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1) rearrangement of methyl group of L-methylmalonyl CoA to form succinyl CoA 2) transfers methyl group from FH4 to homocysteine forming methionine
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What is SAM produced from
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methionine and ATP
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fxn of SAM
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transfers methyl group to precursors that form many cmpds like creatine, phosphatidylcholine, epinephrine, melatonin, methylated nucleotides, and methylated DNA
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only rxn in which methyl-FH4 can donate the methyl group
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creation of methionine from homocysteine
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what occurs id vit B12 or FH4 levels are insufficient
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homocysteine will accumulate
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methyl trap hypothesis
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occurs when vit B12 deficient, methyl unable to leave FH4; folate deficient even though normal amounts present
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what does a folate deficiency lead to
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megaloblastic anemia due to inability of blood cell precursors to synthesize DNA
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schilling test
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ingest radioactive Co60 crystallie vit B12 and 24 hour urine smpl collected; determine amount of B12 absorbed
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5-fluorouracil as chemotherapy agent
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pyrimidine analong which is converted in cells to FdUMP that causes thyminless death and prevent tumor growthl prevents dUMP to dTMP
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what does elevation in methylmalonic acid indicate
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suspect vit B12 deficiency
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why are folate deficiencies common in chronic alcoholics
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inadequate dietary intake, damage to intestines and brush border enzymes, defect in enterohepatic circulation, liver damage, kidney reabsorption
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ineffective erythropoiesis
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increased marrow cellularity, but decreased red cell production
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coemnzyme that fxns in accepting 1-carbon groups
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tetrahydrofolate polyglutamate aka FH4
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3 main structural components of FH4
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1) bicyclic pteridine ring 2) para-aminobenzoic acid 3) polyglutamate tail consisting of several glutamate residues joined in amide linkage
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where is 1-carbon unit accepted/bound in FH4
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N5 or N10 or both
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what does folic acid/folate refer to
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most oxidized form of pteridine ring of FH4
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what reduces folate to dihydrofolate to tertrahydrofolate
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dihydrofolate reductase in cells; reduction is favored direction of rxn
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how do sulfa drugs work against some bacterial infections
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analogs of para-aminobenzoic acid and interfer with synthesis of folate
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US recommended dietary allowance of folate
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400 ug for adult men and women
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good sources of folate
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green leafy vegies, liver, yeast, legumes, some fruits
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what form is the dietary folate from natural sources
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reduced coenzyme form
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how is folate absorbed
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folate conjugases in lumen cleave off glutamate residues producing monoglumate form of folate which is absorbed
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what happens to absorbed folate in intestinal cells
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converted to N5-methyl-FH4 which enters portal vein and goes to liver
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how does N5-methyl-FH4 travel in blood
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loosely bound to albumin and other plasma proteins
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how can folate deficiency be tested
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histidine load test; if folate deficient, then FIGLU appears in urine in excess amounts
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major carbon source of one-carbon groups in human
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serine; hydroxylmethyl group transferred to FH4 via hydroxymethyltransferase
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how is FIGLU (formiminoglutamate) produced
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degradation of histidine
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why does folate deficiency cause DNA synthesis issues
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required in purine base systhesis at carbons 2 and 8; also hindered due to dTMP synthesis
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how does the corrin ring in vit B12 differ from heme
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2 of the 4 pyrrole rings are directly joined rather than by a methylene bridge
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what is within the ring of vit B12 (aka cobalamin)
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Cobalt; can for a bond with a ccarbon atom
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what form is B12 in supplements
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cyanobalamin in which a CN group is linked to the cobalt
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what does methotrexate resemble
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folate except an amino group on C4 and methyl on N10
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what is methotrexate used for
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anticancer drug; inhibit dihydrofolate reductase and prevent conversion of FH2 to FH4
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major source of vit B12
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dietary meat, eggs, dairy products, fish, poultry, and seafood
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2 forms of ingested vit B12
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free or bound to dietary proteins
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what does free B12 bind
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proteins known as R-binders (aka haptocorrins or transcobalamin I)
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where are R-binders produced
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salivary glands and gastric mucosa
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what occurs to haptocorrins in the small intestine
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pancreatic enzymes digest them and release B12 which then binds to intrinsic factor
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what is intrinsic factor
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a glycoprotein secreted by parietal cells in stomach
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where does the intrinsic factor-vit B12 complex attach
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specific receptors in ileum
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Besides pernicous anemia, what other malfunctions can cause vit B12 deficiency
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pancreatic insufficiency or high intestinal pH (too little stomach acid); both prevent degradation of R-binder-B12 complex, so B12 can't bind intrinsic factor
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what rxns is S-adenosylmethionine (SAM) used in
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add methyl groups to either O or N; more than 35 rxns require
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What does folate add 1-carbon groups to
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carbon or sulfur
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examples of SAM use
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guanidinoacetate to creatine, norepinephire to ephinephrine, acetylserotonin to melatonin, and nucleotides to methylated nucleotides; inactivation of catecholamines and serotonin
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what does SAM form when it donates its methyl group
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S-adenosylhomocysteine which is hydrolyzed to form homocysteine and adenosine
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2 major clinical manifestations of vit B12 deficiency
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1) hematopoietic due to folate metabolism 2) neurologic due to hypomethylation in nervous system
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classical clinical presentation of neurologic issues in B12 deficiency
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numbness and tingling of hands and feet, diminished vibratory and position sense, progression to spastic gait disturbance
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what are neurologica symptoms in vit B12 deficiency caused from
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hypomethylation due to inability to recycle homocysteine to methionine and from there to SAM
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what is required for the synthesis of SAM
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methionine-either obtained from diet or through homocysteine
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how do methyl groups get trapped in N5-methyl-FH4
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vit B12 deficiency or methionine synthase enzyme defect
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how is homocysteine synthesized
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S-adenosylhomocysteine (which is hydrolyzed to form homocysteine and adenosine)
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2 fates of homocysteine
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remethylated to methionine or condensed with serine to form cystathionine
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2 routes to methionine production
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N5-methyl FH4 requiring B12 or betaine donates a methyl group to homocysteine in liver
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what does homocysteine to cystathionine require
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PLP
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What occurs with homocysteine if vit B12 not available
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breaks down to form cystathionine which forms cysteine, which is has neg feedback causing accumulation of homocysteine
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what occurs wih enzyme defect in N5, N10-methylene-FH4 to N5-methyl-FH4
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N5-methyl-FH4 too low to convert homocysteine to methionine, causing homocystine elevation
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what occurs when cystathionine B-synthase defect occurs or vit B 6 deficiency
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homocysteine level elvated since conversion to methionine can't accomidate all the homocystine accumulated
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what is choline oxidized to form
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betaine aldehyde, which is oxidized to betaine (trimethylglycine); an alternative route for methionine producation in liver
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how does folate deficiency reduce DNA synthesis
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decreased availability of deoxythymidine and purine nucleotides
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