Ketogenesis

Ketogenesis is the process by which ketone bodies are produced as a result of fatty acid breakdown.

Ketone bodies are produced mainly in the mitochondria of liver cells when carbohydrates are so scarce that energy must be obtained from breaking down fatty acids. Fatty acids are long chains of carbons with an acid group on one end. The body gets energy from fatty acids by breaking the carbon chain down into pieces that contain only two carbon atoms. These pieces are in the form of acetyl-CoA.

The three ketone bodies are acetoacetate, beta-hydroxybutyrate and acetone. (The first two are not technically ketones according to IUPAC nomenclature, but the third is.) Each of these is the product of acetyl-CoA molecules combining to make larger compounds.

Ketogenesis may or may not occur, dependent on how many carbohydrates are available. This is closely related to the paths of acetyl-CoA:

• When the body has sufficient carbohydrates available, glucose is completely broken down to carbon dioxide, with acetyl-CoA as an intermediate, and the CoA is recycled in this process (the citric acid cycle and electron transfer).
• When the body has excess carbohydrates available, some glucose is fully metabolized, some is broken down to acetyl-CoA, but not all the way to CO₂, since not all of that energy is needed yet. Instead, acetyl-CoA molecules are combined to create fatty acids to save for later. (CoA is also recycled here.)
• When the body has no carbohydrates available, fat must be broken down into acetyl-CoA order to get energy. CoA is not being recycled through the citric acid cycle: it is being attached to more and more acetyl groups. You need more CoA to keep breaking down fats, and the only place to get it is from all those acetyl-CoA molecules, by attaching them to each other to get the CoA to fall off.

                                                              COO-                                        COO-
     O                                       O                |         CH3--C(O)--S-CoA                  |
     ||                     CH3              ||               CH2                                         CH2
CH3--C--S--CoA              |         + CH3--C--S-CoA         |              ^            COO-  ------>   |
                            C===O                        HO---C--CH3        /             |              HC--OH   beta-
      +      --------->     |                 \               |            /              CH2             |       hydroxy-
                  \         CH2     ---------------->         CH2      -------------->    |               CH3     butyrate
     O             |        |                     \           |                           C==O            
     ||            V        C===O                  |          C===O                       |      ------>  CH3
CH3--C--S--CoA    CoASH     |                      V          |                           CH3             |       +  CO2
                            S--CoA               CoASH        S--CoA                                      C==O
 2 Acetyl-CoA          Acetoacetyl-CoA                                                Acetoacetate        | 
                                                             HMG-CoA                                      CH3   Acetone

Ketone bodies are created at moderate levels in everyone's bodies, such as during sleep and other times when no carbohydrates are available. However, when ketogenesis is happening at abnormally high levels, the body is said to be in a state of ketosis. It is unknown whether ketosis has negative long-term effects or not.

Both acetoacetate and beta-hydroxybutyrate are acidic, and if levels of these ketone bodies are too high, the pH of the blood drops, resulting in ketoacidosis. This is very rare, and generally happens only in untreated Type I diabetes (see diabetic ketoacidosis) and in alcoholics after binge drinking and subsequent starvation (see alcoholic ketoacidosis).

See also

• ketone bodies
• fatty acid metabolism
• Ketosis

External Links

• Fat metabolism (http://www.unisanet.unisa.edu.au/08366/h&p2fat.htm)
• James Baggott. (1998) Synthesis and Utilization of Ketone Bodies (http://www-medlib.med.utah.edu/NetBiochem/FattyAcids/10_1.html) Retrieved 23 May 2005.
• Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals (http://www.ajcn.org/cgi/content/full/76/1/65), American Journal of Clinical Nutrition.
• Richard A. Paselk. (2001) Fat Metabolism 2: Ketone Bodies (http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n07Dec.htm) Retrieved 23 May 2005.