Analogous to Succinate dehydrogenase

Analogous to fumarase

Analogous to malate dehydrogenase

Claisen cleavage reaction: reverse of citrate synthase

Thiolase

For a saturated fatty acid with n carbon atoms (even number) You make n/2 Acetyl-CoA, which enter TCA cycle to yield n-2/2 NADH n-2/2 FADH 2  -oxidation yields 3n/2 NADH n/2 FADH 2 n/2 ATP 2ATP lost in activation

What about unsaturated fatty acids?

For every double bond that is on a carbon that is an odd number of carbons away from carbonyl: 3 rounds  -oxidation Attempt 4th round Doesn’t work

Ready for another round of oxidation

For every double bond that is on a carbon that is an even number of carbons away from carbonyl: Reductase can’t recognize ∆4 unsaturated fatty acids as a substrate 5 rounds  -oxidation

Just reduce the double bond Resume oxidation with the cost of 1 NADPH which ultimately costs one NADH

What about fatty acids with odd number carbons Last round produces propionyl-CoA instead of Acetyl-CoA

One extra ATP is consumed to convert propionyl-CoA to succinyl-CoA For odd chain fatty acids You make n-3/2 Acetyl-CoA and one propionyl-CoA Succinyl-CoA enters TCA cycle This is can be used as an anapleurotic rxn or the succinyl-CoA can be converted to malate. In the latter case.....

Conversion of succinyl-CoA to malate makes 1ATP, 1 FADH 2

Malate pyruvate Acetyl-CoA +1NADPH is converted to NADH 3NADH + 1FADH 2 + ATP Malic enzyme - decarboxylating +1NADH

One extra ATP is consumed to convert propionyl-CoA to succinyl-CoA So.....for odd chain fatty acids You make n-3/2 Acetyl-CoA and one propionyl-CoA One ATP and one FADH 2 are made to convert succinyl-CoA into malate One NADH is made converting malate into Acetyl- CoA 3NADH, 1ATP and 1FADH 2 are made oxidizing the Acetyl-CoA Net 1 propionyl-CoA = 2FADH 2 + 4NADH + 1ATP

In plants the peroxisome is the major site of  - oxidation. In animals the peroxisome is mainly responsible for oxidation of very long chain fatty acids. The first step is different because there is no enzyme that can directly inject electrons into the e- transport chain. Instead electrons are put directly onto O 2 by an FAD- dependent oxidase. This generates H 2 O 2 which must be degraded by catalase.

Ketone Bodies Liver Muscle

Other sources of central metabolites?

Goin’ Backwards Can you run these pathways in reverse to make glucose?

Can the TCA cycle be run in reverse?

The Reductive TCA cycle How do you reverse  -KGDH? Ketoglutarate synthase 2-oxoglutarate:ferredoxin oxidoreductase Hydrogenase takes electrons from H 2 and gives them to ferredoxin which ultimately puts them on  -KG.

What about isocitrate dehydrogenase? This step can be made reversible if you use a different source of electrons. Use NADPH instead of NADH.

Citrate lyase

Pyruvate synthase Acetyl-CoA + CO 2 ---> pyruvate Pyruvate:ferredoxin oxidoreductase Uses TPP and is essentially the same mechanism Except that the electrons come from H 2

The TCA cycle cannot convert Acetyl-CoA into malate. Malate is only part of a pathway to regenerate the catalyst. Malic enzyme decarboxylating

What if you could skip the decarboxylation steps? Pyruvate

Claisen condensation

Isocitrate lyase Related to enolase

2Acetyl-CoA + NAD + + 2H 2 O ---> succinate + 2CoA + NADH + H + Succinate enters TCA cycle and is converted to oxaloacetate with the generation of FADH 2 and NADH Oxaloacetate is converted to PEP Notice that acetyl-CoA can only be converted to glycolytic intermediates if there is a glyoxalate cycle or a pyruvate synthase

Reversing homolactic fermentation This reaction is reversible in liver and muscle ∆G ~ 0

What about ethanolic fermentation? Irreversible What about going from acetaldehyde to acetyl-CoA?

Aldehyde dehydrogenase: similar to glyceraldehyde DH