cis-δ 3 -enoyl CoA TCA cycle

Transcription

1 ession 15 - hemical Interlude - Why did we have to use a thioester (Fcyl o)? -- The reverse reaction (decarboxylation of β-keto acid) is VEY favorable. 2 βkt o X 2 annot do this with a carboxylic acid - unfavorable ecall how to make a thioester from an acid: MP +TP MP +PP i βkt o o pecial ase 1 - F has a is-double bond -- is-double bonds promote membrane plasticity -- trans-double bonds have a slight reduction in overall energy yield -- ut, is-double bonds present a biochemical challenge to digestion -- For example, leic cid (18:1)Δ9 -- The word "oil" comes from oleic (olive oil = oleic)... o cis-δ 3 -enoyl o leyl o Isomerase leyl o o trans-δ 2 enoyl o 1 19 o tep I ould phosphorylation work? - Probably. MP (and phosphate) are good leaving groups pecial ase 2 - dd hain F: Introduction to arboxylases Pentadecanoic acid (15:0) = 1.2% of milk fat 6 cetyl o " 2 " inserted α-carbon; must activate 2 for it to add to α o TP Pentadecanoyl o rounds of β- oxidation Propionyl o o o (iotin) Propionyl o arboxylase 2 2 several steps o uccinyl o carbon skeleton rearrangement (Vitamin 12 ) o T cycle -- dd chain F in diet uccinyl o (-4) ydratase regular β-oxidation cetyl o (many) Propionyl o (-3) -- They are anapleurotic (increase rate of T cycle) -- They can be gluconeogenic (later) can result in net synthesis of glucose from this part of the F chain (the cetyl o-derived units are typically not gluconeogenic unless glyoxylate cycle (later) is operative) -- The carboxylase family does much more than metabolize odd chain F " 2 " D

2 More General View of arboxylases -- equire biotin (Vit. 7 ), 2 and TP -- Increase size of molecule by one carbon (as " 2 ") -- This is a kind of carbon fixation -- Play a role in: (a) dd chain F metabolism Example: Propionyl o arboxylase * We'll look at this in detail later (this is also anapleurotic) (b) F biosynthesis Example: cetyl o arboxylase (c) napleurosis and Gluconeogenesis Example: Pyruvate arboxylase 3 " 2 " 3 " 2 " 3 " 2 " o o 2 tart with (c) - Pyruvate arboxylase ( P ) G ole: To P [xaloacetate] in mitochondrion always limiting Mitochondrion P co -- P stimulated by co T F β- oxidation -- This regulatory mechanism keeps rate of T matched to rate of generation of co 3 " 2 " 2 2 rate of T cycle

3 teps (most are common to all carboxylases) ) ynthesis of icarbonate via arbonic nhydrase ( ) 2.) iotin arboxylase ( ) eaction of Pyruvate arboxylase ( P ) not very soluble in water + "ydrated 2 " 2 cont.) iotin arboxylase eaction of Pyruvate arboxylase ( P ) P We use a high Energy bond to "dehydrate" bicarbonate in active site of enzyme P i [ ] of 2 in active site very soluble N N 14 P ubstrate (pyruvate) iotin will hold 2 temporarily 2 + TP DP + P carbonyl (or carboxy) phosphate 3.) arboxytransferase ( T ) eaction of P (from above) N N P 2 P Pyruvate enolate 2 3 2

4 ow to Visualize arboxylase hemistry -- T and are ~55 apart -- swinging arm does the " 2 " transfer Example (b) - cetyl o arboxylase -- Exactly the same chemistry, but acetyl o receives the arboxytransferase (T) ite TP 2 3 iotin arboxylase () ite 1 2 N 1 Pyruvate enolate N 2 Delivers " 2 " to substrate (pyruvate enolate) at second site on P enzyme (using the same swinging arm) ( T reaction) Flexible arm Picks up 2 from iotin arboxylase subunit ( reaction) 3 o " 2 " TP 2 Malonyl o o -- Malonyl o is the precursor to most of the ethylene units in Fs -- We'll see this again soon when we talk about F biosynthesis Example (c) - Propionyl o arboxylase - followed by synthesis of uccinyl o (2 more steps) Introduced 2 pages back (i) dd hain F (ii) Ile, Met, Val, Thr 3 2 o Propo arboxylase Mechanism as above 2 [ 2, TP] 3 o -Methyl-Malonyl o Me-Malonyl o Epimerase (think about this mechanism) 2 o -Methyl-Malonyl o Me-Malonyl o Mutase denosylcobalamin (from Vitamin 12 ) reverses positions of and o 2 o redraw o uccinyl o feeds into T co I αkg o o the concentration of intermediates in T cycle

5 MIT penourseware iological hemistry I Fall 2013 For information about citing these materials or our Terms of Use, visit: