Term
| What is the active methyl donor? |
|
Definition
| S-Adenosylmethionine. Methionine+3ATP-->SAM+3Pi (via methionine adenosyl transferase) |
|
|
Term
| Basic steps of active methyl cycle? |
|
Definition
| Methionine-->SAM-->SAH-->Homocysteine-->Methione (last regeneration step by homocysteine methyl transferase, using B12 and CH3 from N5methylTHF) |
|
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Term
| What pathways can homocyteine take and why would it choose either? |
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Definition
| 1)Regeneration to Methionine, 2)Transsulfuration pathway = Homocysteine+Serine-->Cysteine+NH3+aKB, does this if sufficient methionine in diet. |
|
|
Term
| What part of ATP adds to Methionine to make SAM? |
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Definition
|
|
Term
| Some critical biochemical rxns produced from methylation rxns? |
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Definition
| Epinephrine, creatine, methylated nucleotides, phosphtidyl choline, melatonin. |
|
|
Term
| What is the fate of homocysteine's carbons after transsulfuration? |
|
Definition
| aKB-->Propionyl CoA-->Methylmalonyl CoA--> SuccCoA-->TCA cycle or OAA for gluconeogenesis. |
|
|
Term
| How does homocysteine contribute to cardiovascular disease? |
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Definition
| Causes proliferation of smooth muscle cells that line arteries, also generates ROS which --> foam cells. |
|
|
Term
| Which co-factors are reqd to regenerate Methionine from Homocysteine? |
|
Definition
| B12 (cobalamine), N5-CH3-THF |
|
|
Term
| Co-factor reqd for transsulfuration pathway? |
|
Definition
| B6=PLP, req'd by both steps. |
|
|
Term
| Which are the 2 mammalian rxns requiring B12? |
|
Definition
| Homocysteine-->Methionine, PropionylCoA-->-->SuccCoA |
|
|
Term
| Why is cysteine such an important AA? |
|
Definition
| One of 3 that makes up GSH, reqd for protection against oxidative stress |
|
|
Term
| Potential causes of hyperhomocysteinemia? |
|
Definition
| In methyl cycle: 1)B12 deficiency, 2)def in enzyme that converts N5,N10methyleneTHF --> N5methylTHF, in transsulfuration pathway 3)mutated cysteine synthase or B6 def. |
|
|
Term
| Symptoms of elevated cysteine levels? |
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Definition
| Neurological impairments/developmental probs, skeletal abnormalities, dislocation of lens, vomiting/GI irritability. |
|
|
Term
| How is hyperhomocysteinemia treated? |
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Definition
| Depends on cause; 1)Supp w B12, B6, folate, enzymes, 2)Reduce Methionine intake - difficult bc essential so req's adding Cysteine as well. |
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Term
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Definition
| B-vitamin crucial for growth and development. |
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Term
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Definition
| Reduced (functional) form of folic acid. |
|
|
Term
| How are the one C fragments stored and where are they from? |
|
Definition
| Folate pool; mainly from serine, glycine, histidine. |
|
|
Term
| Which important biochemical does each form of carbon from folate pool play an important role in producing? |
|
Definition
N5CH3THF - regeneration of Methioine from Homocysteine,
N5,N10CH2THF - synth of dTMP from dUMP,
N5,N10CHTHF - synth of purine rings |
|
|
Term
| How does folate def --> anemia & growth failure? |
|
Definition
| Reduced ability to synth dTMP --> reduced DNA replication and reduced purine synthesis. |
|
|
Term
| What causes Fetal Alcohol Syndrome? |
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Definition
| 1 reason is alcohol interferes w folic acid absorption. |
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|
Term
|
Definition
| Prevent synth of folic acid --> kills penicillin resistant bacteria but doesn't hurt us bc we don't synth folic acid. |
|
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Term
| How is THF regenerated in the production of dTMP from dUMP? |
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Definition
| 2 Hs from THF (FH4) are used to reduce the carbon donated form dTMP to the methyl level leaving us w DHF. DHF+NADPH--->THF+NADP via DHF Reductase. |
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Term
| How do anti-tumor drugs that inhibit folic biochem work? |
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Definition
| Cancer cells need to make a lot of dTMP for DNA synth. Drugs can inhibit this in diff ways ie 1) Methotrexate inhibits DHF Reductase, 2) 5FU inhibits thymadilate synthase (dUMP+N5,N10CH2THF-->dTMP+DHF) |
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|
Term
| How does folic acid biochem play a role in purine synth? |
|
Definition
| N5,N10methenylTHF (CH) make C2 & C8 of purine ring. |
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Term
| How can histidine be used to test for THF def? |
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Definition
| Histidine-->N-Formamino glutamate which + THF --> N5FormaminoTHF + glutamate. If inject lrg amounts of histidine and N5FormaminoTHF does not form = THF deficiency. |
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Term
| How are the 3 oxidation stated of 1 C grps carried by THF related? |
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Definition
| N5,N10-CH-THF reduced --> N5,N10-CH2-THF (or opp = methylene oxidized-->methenyl); N5,N10-CH2-THF reduced --> N5-CH3-THF. |
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|
Term
| How are serine & glycine related? |
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Definition
| Serine+THF<-->Glycine+N5N10-CH2-THF; Glycine+THF+NAD<-->N5N10-CH2-THF +CO2+NH3+NADH |
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|
Term
| What co-factor is reqd to get Cs from serine & glycine into folate pool? |
|
Definition
|
|
Term
|
Definition
| 4 pyrrole units = corrin ring + ctr cobalt |
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|
Term
|
Definition
| 1)w Methyl --> Methyl Cobalamine, 2)w Deoxyadenosine --> Deoxyadenosyl Cobalamine |
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|
Term
| Which cmpds are ultimately converted to SuccCoA, therefore requiring B12? |
|
Definition
| Threonine, Isoleucine, Methionine, Valine, odd-chain FAs. |
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|
Term
|
Definition
| 1)Enters TCA cycle, 2)Oxidized-->OAA-->gluconeogenesis |
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|
Term
| What causes methylmalonyl aciduria? |
|
Definition
| 1)Def of Methylmalonyl CoA Mutase, 2)B12 def , 3)Adenosyl Transferase def. All lead to inability to convert Methylmalonyl CoA-->SuccCoA either by a def of the enzyme, the enzyme's co-factor, or the enzyme that attaches deoxyadenosyl to B12. |
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|
Term
| Symptoms of methymalonyluria? |
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Definition
| Nausea, vomiting, convulsions, retardation, early death. |
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Term
| Treatment of methylmalonyluria? |
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Definition
| Synthetic protein diet that eliminates/limits the 4AAs that breakdown --> propionylCoA (threonine, isoleucine, methionine, valine), difficult bc all essential. |
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|
Term
| What causes Pernicious Anemia? |
|
Definition
| Def of IF --> reduced B12 absorption --> folic acid accumulates as N5-CH3-THF due to inability to convert homocysteine+N5-CH3-THF--> methionine+THF; for some unknown reason body reacts as if def in N5-CH3-THF so all other forms of folic acid reduced to N5-CH3-THF --> no methylene for dUMP-->dTMP, no methenyl for purine synth --> RBCs cannot divide normally. |
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|
Term
| How is Pernicious Anemia treated? |
|
Definition
| Cobalamine (B12) injection. |
|
|
Term
| Which 2 biochemical pathways req B12(cobalamine)? |
|
Definition
| 1)Regeneration of Methionine from Homocysteine, 2)Methylmalonyl CoA-->SuccCoA (end of transsulfuration pathway) |
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|
Term
| Fxns of nucleotides in biological systems (5). |
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Definition
| 1)Activated precursors of RNA/DNA, 2)Activated intermediates in biosyntheses (ie SAM methylation), 3)ATP as energy, 4)Component of NAD & FAD, 5)Metabolic regulators (ie AMP) |
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|
Term
|
Definition
|
|
Term
|
Definition
| Cytosine, Uracil, Thymadine. |
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|
Term
| De Novo synth of purine bases: |
|
Definition
| R5P+ATP-->PRPP, PRPP+Glutamine+Glycine+Glutamine+Aspartate+N5,N10CHTHF-->IMP-->AMP or GMP. |
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|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the first purine to be synth by the de novo pathway? |
|
Definition
| Inosine, has hypoxanthine base. |
|
|
Term
| Role of folate in purine synth? |
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Definition
|
|
Term
| Where does ribose sugar come from? |
|
Definition
|
|
Term
| What directs whether IMP will be converted to GMP or AMP? |
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Definition
| Both inhibit their own synthesis, AMP reqs GTP, GMP reqs ATP. |
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Term
| Rate limiting step of purine synth and how is it regulated? |
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Definition
| PRPP+Glutamine-->5-phosphoribosyl-1-amine via amido phosphoribosyltransferase. Inhib by IMP, AMP, GMP (products). |
|
|
Term
| What happens to the bases when RNA is broken down? |
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Definition
| 1)Excreted as uric acid or 2)Returned to purine nucleotide pool via purine salvage pathway. |
|
|
Term
| Basic mech of purine salvage pathway? |
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Definition
| Rather than being excreted as uric acid, purine base is attached to PRPP --> ribonucleotide. |
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Term
| What results from a def of hypoxanthine-guanine phosphoribosltransferase? |
|
Definition
| Lesch-Nyhan syndrome -->compulsive self-destruction, elevated PRPP, incr in de novo purine synth, overproduction of urate from purine base breakdown-->kidney stones/gout. |
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|
Term
|
Definition
| High meat diets, excess alcohol, kidney disease, Lesch-Nyhan --> high lvls of uric acid in blood --> reacts w metals --> urate forms insoluble crystals which deposit in joints -->attacked by immune system. |
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|
Term
|
Definition
| 1)Allopuranol - inhibits xanthine oxidase so purines only breakdown to hypoxanthine/xanthine which are more soluble and easier to excrete, 2)Methotrexate/Colchicine block immune system & inflammatory rxns. |
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|
Term
| How does purine breakdown play a role in ischemia reperfusion injury? |
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Definition
| The breakdown of ATP (via this pathway)-->xanthine, xanthine oxidase creates free radical (H2O2). |
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Term
| Where would you find CPSI vs CPSII? Why is this important? |
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Definition
| CPSI in liver mito (urea cycle), CPSII in all cell cyto (catalyzes 1st step of pyrimidine biosynth). Keeps pathways separated. |
|
|
Term
| Fxn of Ribonucleotide Reductase? |
|
Definition
| Reduce ribonucleotides to deoxyribonucleotides. |
|
|
Term
| Rate limiting step of pyrimidine biosynth? How is it regulated? |
|
Definition
| CarbamoylP+Aspartate-->N'carbamoyl Aspartate + Pi via Carbamoyl Aspartate Transcarbamylase. Inhib by pyrimidines, stim by ATP (a purine). |
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|
Term
|
Definition
| Inbib by UMP (product), stim by PRPP. |
|
|
Term
| How are the urea cycle and pyrimidine synth interrelated? |
|
Definition
| Orotic acid; OTC def-->CarbamoylP accumulation-->orotic acid or can leave mito and join pyrimidine synth --> UMP. |
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|
Term
| Oxidation/Reduction steps of Ribonucleotide Reductase? |
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Definition
| Uses NADPH to reduce ribose-->deoxyribose; thioredoxin reduces reductase disulfide back to sufhydryl state using FADH2; NADPH reduces FAD back to FADH2. |
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|
Term
| What are the 3 "sites" on RR? |
|
Definition
| 1)Overall activity site, 2)Substrate specificity site, 3)Catalytic site. |
|
|
Term
| What does catalytic site of RR contain? |
|
Definition
| 1)Essential sulfhydryl grps, 2)Iron-Oxygen complex (powerful oxidant!), 3)Tyrosine residues. |
|
|
Term
| How can RR be targeted to fight cancer? |
|
Definition
| Hydroxyurea quenches tyrosine free radical --> cells no longer divide. |
|
|
Term
| How do tyrosines on RR extract Hs from ribonucleotides? |
|
Definition
| Via generation of a free radical. |
|
|
Term
| How does RR substrate specificity site work? |
|
Definition
| ATP (a purine) binds activity site --> forms deoxypyrimidines (dCDP, dUDP) --> either dCDP or dTTP displaces ATP --> signifies enough pyrimidines so switches to producing purines --> dGTP displaces dTTP --> makes other purine (dATP) --> dATP displacing dGTP turns system off. |
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|
Term
|
Definition
| Deficiency in adenosine deaminase (which catalyzes AMP-->hypoxanthine in purine uric acid pathway), if adenosine isnt getting broken down neither is deoxyadenosine (dATP) so RR is constituitively turned off --> no WBC division --> no Abs. |
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|
Term
| Glucogenic and Ketogenic metabolites produced by AA catabolism. |
|
Definition
Glucogenic: Pyruvate, aKG, SuccCoA, Fumarate, OAA.
Ketogenic: Acetoacetate, AcCoA. |
|
|
Term
| Which tissues breakdown AAs and why? |
|
Definition
| All tissues, esp liver & muscle. AAs can't be stored. |
|
|
Term
| Which is the only purely ketogenic AA? |
|
Definition
|
|
Term
| Which AAs break down to pyruvate? |
|
Definition
| Tryptophan, Alanine, Glycine, Serine, Cysteine. |
|
|
Term
| AAs that break down to aKG? |
|
Definition
| Glutamine, Glutamate, Histidine, Proline, Arginine. |
|
|
Term
| AAs that break down to SuccCoA? |
|
Definition
| Methionine, Threonine, Isoleucine, Valine. |
|
|
Term
| AAs that break down to OAA? |
|
Definition
|
|
Term
| AAs that break down to fumarate? |
|
Definition
|
|
Term
| Which AA do sulfates come from and what are they used for? |
|
Definition
| Cysteine; Remove toxins from body, steroids circulate as ester-sulfates, component of joint glycoproteins. |
|
|
Term
| Which are the branch chain AAs and how are they broken down? |
|
Definition
| Leucine, valine, isoleucine. Transamination --> aKetoAcid of AA --> CoA derivative (by aKetoAcid DH) -->other CoAs (by acyl CoA DH). |
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|
Term
| Deficiency of aKetoAcid (branched chain) dehydrogenase causes what? |
|
Definition
| MSUD; build up of branched-chain AAs & aKetoAcids; very toxic to nervous system --> failure to thrive, coma, death before age 2 if untreated. |
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|
Term
|
Definition
| Synthetic protein diet restricting branch-chain AAs. |
|
|
Term
| What does phenylalanine break down to and what is the necessary co-factor? |
|
Definition
| Phenylalanine-->Tyrosine-->Fumarate+AcetoAcetate; THB (tetrahydrobiopterin), donates Hs (similar to THF), regenerated DHB-->THB via DHB reductase+NADH. |
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|
Term
| What does a def in phenylalanine hydroxylase cause and how is it treated? |
|
Definition
| Phenylketonuria (PKU); built up phenylalanine enters side pathways --> phenylpyruvate & phenylacetate (phenylketones) --> severe neurological disturbances. Treat by restricting phenylalanine + supplementing w tyrosine. |
|
|
Term
| What besides a def in phenylalanine hydroxylase can cause PKU and how is it treated? |
|
Definition
| THB def, supplement. DHB reductase def, v difficult to treat. |
|
|
Term
|
Definition
| Alkaptonuria= def of homogentisic acid oxidase (tyr-->homogentisate-->fumarate); also req a lot of Vit C; assoc w severe arthritis. |
|
|
Term
| Which AAs are both ketogenic and glucogenic? |
|
Definition
|
|
Term
| What co-factor is reqd as a reducing agent for aromatic AA hydroxylation? |
|
Definition
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