BIOC 503 - Fatty Acid Oxidation & Ketogenesis

odd numbered

If the double bond in unsaturated fatty acid is in an ____ position, then:

1. regular B-oxidation cycles happen until the carbon before the double bond is reached.

2. enoyl-CoA isomerase changes double bond conformation from cis to TRANS between alpha and beta carbons

3. SKIP first step of next B-oxidation cycle aka dehydrogenation (thus does no FADH2 produced, aka loss of 1.5 ATP produced)

1.5

B-oxidation of unsaturated fatty acid lose ___ ATP for EACH double bond in the molecule

• because the first dehydrogenation step making FADH2 is skipped

• before and after double bon cycles are NOT affected

even numbered

If the double bond in unsaturated fatty acid is in an ____ position, it is usually right after another double bond, then:

• Normal B-oxidation cycle until the carbon before the FIRST double bond reached

• next cycle deals with FIRST double bond by isomerization and normal B-oxidation

• To deal with the SECOND double bond: normal dehydrogenation making FADH2

• dehydrogenation step using NADPH and reductase enzyme (merge the 2 double bonds into 1)

• isomerization by enoyl-CoA isomerase to change the new double bond position

• normal B-oxidation remaining steps

same

Because of the extra dehydrogenation step using NADPH required for EVEN numbered position double bond, it produces the ___ number of ATP molecules as normal B-oxidation per cycle.

2

When asking about the ATP production of the oxidation of free fatty acids, then we need to subtract the __ ATP needed to activate them to fatty acyl-CoA molecules

propionyl-CoA

fatty acid with ODD number of carbons leave ___ after the last round of B-oxidation, just like BRANCHED fatty acids do

succinyl-CoA

propionyl-CoA produced from oxidation of ODD number of carbon fatty acids and branched fatty acids is made into ___ which goes back to TCA cycle and thus is glucogenic

methyl groups

The added ___ of=n the hydrocarbon chains of BRANCHED fatty acids do NOT interfere with B-oxidation

production of succinyl-CoA

1. propionyl-CoA + carbonate + ATP + biotin = D-methylmolonyl-CoA + ADP + Pi via propionyl-COA carboxylase (ATP dependent)

2. D-methylmalonyl-CoA + epimerase = L-methylmalonyl-CoA

3. L-methylmalonyl-CoA + mutase + coenzyme B12 = succinyl-CoA

gluconeogenesis

Because fatty acid oxidation making succinyl-CoA happens under low-glucose conditions, so succinyl-CoA goes back into the TCA cycle to make oxaloacetate for the ___ pathway

peroxisome, 20

An alternative pathway for fatty acid oxidation can be found in ___ which is specific for VERY LONG chain fatty acids, aka over __ carbons long

shorter

The main function of the peroxisome fatty acid oxidation pathway is to make VERY LONG chain fatty acids __ so that they and the produced acetyl-CoA can be sent into the mitochondria

liver mitochondria

The ketogenesis pathway happens in the ___ and produces 3 kinds of ketone bodies

ketone bodies

• acetoacetate

• acetone (excreted via sweat and breath)

• B-hydroxybutyrate

acetyl-CoA

ketone bodies are produced from excess ___ from B-oxidation

energy sources

acetoacetate and B-hydroxybutyrate are both exported to extrahepatic tissues as ___

ketone bodies production

1. 2 acetyl-CoA + thiolase = acetoacetyl-CoA

2. Acetoacetyl-CoA + HMG-synthase = HMG-CoA

3. HMG-CoA + lyase = acetoacetate

4. acetoacetate + decarboxylase = acetone

4. acetoacetate + dehydrogenase = B-hydroxybutyrate

HMG-synthase

Main point of regulation for ketone bodies formation and also cholesterol synthesis

• important enzyme

B-hydroxybutyrate

During prolonged fasting, the brain adapts to use ___ as a source of energy

beta-ketoacyl-CoA transferase

__ is the key enzyme for extrahepatic tissues to use ketone bodies.

• use succinyl-CoA to make acetoacetyl-CoA and succinate

• induced in brain during fasting period

• NOT present in liver as it can make ketone bodies but NOT use them

biological functions of ketogenesis

• remove excess acetyl-group from fatty acid oxidation

• maintain CoA pool for other metabolic pathways in liver

• provide ketone bodies as alternative energy for extrahepatic tissues

diabetes

__ causes HIGH amount of ketone bodies in the blood because cannot use glucose properly to support the body

• causes breath to smell like acetone

• can cause acidosis (acidic blood)

increases, decreases

Acetyl-CoA __ ketogenesis because substrate, and __ citric acid cycle because happens under LOW GLUCOSE conditions

malonyl-CoA 

Carnitine shuttle is inhibited by ____