Vitamins 3

are alpha or beta keto acids easily decarboxylated?

beta

the reason beta keto acids are easily decarboxylated is because of the formation of an..

enolate stabilised as a carbanion

direct decarboxylation of an alpha keto acid would require production of an … which represents a huge energy barrier and isn’t possible

acyl anion

examples of 3 alpha keto acids which are decarboxylated in oxidative metabolism (and the products of their decarboxylations)

1. pyruvate → acetyl coa + co2

2. OAA → PEP + co2

3. alpha KG → succinyl coa + co2

vit B1 facilitates decarboxylation of alpha keto acids through a mechanism which involves the formation of an…

intermediate which is structurally equivalent to a beta keto acid

draw the thiazolium ring of B1

ok

the carbon at C2 in the thiazolium ring is readily … producing a … which can act as a powerful … and can target weak …

deprotonated, carbanion, nucleophile, electrophiles

only 5 human enzymes require TPP 3 of them catalyse … another is … in the … pathway and the last is involved in … in the …

decarboxylation of alpha keto acids, transketolase, pentose phosphate, degradation of fatty acids, peroxisomes

5 human enzymes which use TPP as a cofactor (don’t have to name the last one just say what its involved in and in which organelle)

1. pyruvate dehydrogenase

2. phosphoenolpyruvate carboxykinase

3. alpha KG dehydrogenase

4. transketolase

5. involved in degradation of fatty acids in peroxisomes

revise the mechanism of how TPP thiazolium ring reacts with an alpha keto acid

ok

two rings on B1

aminopyridine and thiazolium ring

main catalytic chemistry of B7 occurs on which ring

ureido ring

the … of the ureido ring is weakly …

N1, nucleophilic

the N1 of the ureido ring (weakly nucleophilic) serves as a … of …

carrier of co2

3 processes which use B7 as a cofactor (for carboxylation)

1. FA synthesis

2. pyruvate metabolism

3. gluconeogenesis

2 examples of enzymes using biotin (B7) as a cofactor

1. acetyl coa carboxylase

2. pyruvate carboxylase

2 catalytic domains of pyruvate carboxylase

1. BC - biotin carboxylase

2. CT - carboxyltransferase

what is the carrier domain in pyruvate carboxylase which holds biotin (covalently linked to a Lys by an amide bond)

BCCP - biotin carboxyl carrier protein

enzyme complexes are big and biotin allows movement of a … group between the different … domains

carboxyl, catalytic

how many identical subunits does pyruvate carboxylase have

4

does each subunit in pyruvate carboxylase contain BC (biotin carboxylase), CT (carboxytransferase) and a BCCP (biotin carboxyl carrier protein)?

yes

the biotin (B7) arm on pyruvate carboxylase usually swings between the … active site of its own subunit and the … active site of the opposing antiparallel neighbouring subunit

BC, CT

how many angstroms Å long is the mobile arm of biotin and lysine?

16

biotin is carboxylated in the BC active site by … and …

bicarbonate and ATP

lipoic acid is a mobile … carrier

acyl

… plays the role of a swining arm in FA synthesis as part of the … domain

phosphopantetheine, ACP

what is the name of the functional arm of CoA and ACP? (derived from pantothenic acid)

phosphopantetheine

revise the mechanism of biotin-dependent carboxylation (slides 47&48)

ok

THF is produced from folate in a 2 step … reaction by the enzyme … using … as a reducing agent

reduction, dihydrofolate reductase, NADPH

which 4 foods have folate? (note: there are more obv but these are the main examples)

dark green leafy vegetables, fruits, nuts and pulses

recommended daily allowance of folate for adults, pregnant women and children aged 4-8 in µg

400, 600 and 200

B9 deficiencies in developing children cause … defects, … bifida and …phaly

neural tube, spina bifida and anencephaly

biotin carries … as a … group in … reactions (adds a C to a substrate)
THF carries a … unit in several … states (methyl, methylene, formyl itd) and is used in … reactions

co2, carboxyl, carboxylation, one carbon, oxidation, biosynthesis

three parts of folate

pteridine ring, PABA and glutamate

what does PABA stand for?

p aminobenzoate

which two N atoms act as the site of addition of one carbon units

N5 and N10

N… of the … ring and N… of the … are … and act as … ( this is about folate structure)

5, pteridine, 10, PABA, basic, nucleophiles

3 different one carbon forms of THF

1. n5 methyl THF

2. n10 formyl THF

3. n5, n10 methylene THF

addition of methylene to THF (enzyme abbreviation)

… + … → … + …

serine + THF → N5, N10 methylene THF + glycine (SHMT)

what does the enzyme name SHMT stand for

serine hydroxymethyl transferase

different oxidation states of THF arise due to … changes to the attached … unit

redox, c1

… is converted to … by thymidylate synthase converting … into … (B9)

deoxyuridine monophosphate, deoxythymidylate, n5, n10 methylene THF, DHF

which oxidation state of THF is used in pyrimidine synthesis?

n5, n10 methylene THF

which form of THF is used in purine synthesis?

n10 formyl THF

which form of THF is used in methionine regeneration from homocysteine?

n5 methyl THF

2 carbons of purines come from one carbon unit transfers from … generating …

n10 formyl THF, THF

what is generated when n5 methyl THF donates the one carbon unit to homocysteine?

THF and methionine

which enzyme converts DHF back to THF

DHF reductase

which molecule inhibits DHF reductase

methotrexate

methotrexate inihibits DHF reductase and is an important …, … and … drug

anticancer, immunosuppressant and antiparasite

3 main parts of the cobalamin structures

beta axial ligand, tetrapyrrole corrin ring and alpha axial ligand

the beta axial ligands in cobalamin vary but the two biologically active ones are…

methylcobalamin and adenosylcobalamin

which metal is at the center of the pyrrole corrin ring in B12

cobalt III

which oxidation state of cobalt in the pyrrole corrin ring of B12 is regarded as a super nucleophile

Co I

B12 is only synthesised by…

bacteria

B12 is escorted on … everywhere from dietary intake to final enzyme use

proteins

in humans B12 is synthesised by our …

gut microbiome

which reaction utilises adenosyl-B12

… → … (enzyme)

methylmalonyl CoA → succinyl CoA (methylmalonyl coa mutase)

the conversion of methylmalonyl coa to succinyl coa allows … amino and fatty acids to be fed into the TCA cycle

branched

which reaction utilises methyl-B12

… → … (enzyme)

homocysteine → methionine (methionine synthase)

when B12 is deficient and N5 methyl THF accumulates (no N5, N10 methylene or N10 formyl THF), DNA synthesis cannot proceed which results in severe … because erythropoiesis cannot proceed

anemias