Ketogenic amino acid

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Three compounds acetoacetate, P-hydroxybutyrate, and acetone, are known as ketone bodies. They are suboxidized metabolic intermediates, chiefly those of fatty acids and of the carbon skeletons of the so-called ketogenic amino acids (leucine, isoleucine, lysine, phenylalanine, tyrosine, and tryptophan). The ketone body production, or ketogenesis, is effected in the hepatic mitochondria (in other tissues, ketogenesis is inoperative). Two pathways are possible for ketogenesis. The more active of the two is the hydroxymethyl glutarate cycle which is named after the key intermediate involved in this cycle. The other one is the deacylase cycle. In activity, this cycle is inferior to the former one. Acetyl-CoA is the starting compound for the biosynthesis of ketone bodies. 

Following their deamination, several amino acids can be converted into oxaloacetate via pyruvate or other components of the TCA cycle these are termed glucogenic amino acids because their carbon atoms may eventually appear in glucose (see Table 6.7). The carbon skeletons of other amino acids may be converted into acetyl-CoA or acetoacetyl-CoA and these are ketogenic amino acids. A few amino acids be metabolized through both glucogenic and ketogenic pathways. 

Glucogenic amino acids Ketogenic amino acids Amino acids that are glucogenic and ketogenic... 

The cyde is central to the oxidation of any fuel that yields acetyl CoA, induding glucose, fritty acids, ketone bodies, ketogenic amino acids, and alcohol There is no hormonal control of the cyde, as activity is necessary irrespective of the fed or fasting state. Control is exerted by the energy status of the cell. 

Ketogenic amino acids yield acetyl CoA and acetoacetate. 

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

Amino acids that give rise to ketone bodies (acetylCoA or acetoacetyl-CoA, neither of which can bring about net glucose production) are called ketogenic amino acids. Leucine and lysine are ketogenic amino acids. Some amino acids, e.g. threonine, isoleucine, phenylalanine, tyrosine and tryptophan, can be both ketogenic and glycogenic. 

Leucine, isoleucine, lysine, and tryptophan form acetyl CoA or ace toacetyl CoA directly, without pyruvate serving as an intermediate (through the pyruvate dehydrogenase reaction, see p. 107). As men tioned previously, phenylalanine and tyrosine also give rise to acetoacetate during their catabolism (see Figure 20.7). Therefore, there are a total of six ketogenic amino acids. 

Lysine, an exclusively ketogenic amino acid, is unusual in that nei ther of its amino groups undergoes transamination as the first step in catabolism. Lysine is ultimately converted to acetoacetyl CoA. 

Definition of ketogenic amino acids, and examples of the prod ucts made from them... 

According to a long-used classification amino acids are ketogenic if (like leucine) they are converted to acetyl-CoA (or acetyl-CoA and acetoacetate). When fed to a starved animal, ketogenic amino acids cause an increased concentration of acetoacetate and other ketone bodies in the blood and urine. On the other hand, glucogenic amino acids such as valine, when... 

Leucine is known as a "ketogenic" amino acid. Explain what this means. 

Ketogenic Amino Acids Which amino acids are exclusively ketogenic ... 

Transamination reactions produce pyruvate, and deamination followed by degradation of the carbon skeleton of ketogenic amino acids produces acetyl-CoA (see Chap. 15). 

A smaller number of amino acids are degraded to acetyl-CoA or acetoacetyl-CoA. Neither acetyl-CoA nor acetoacetyl-CoA can yield a net production of oxaloacetate, the precursor for the gluconeogenesis pathway (because for every 2-carbon acetyl residue entering the TCA cycle, two carbon atoms leave as CO2). These are referred to as the ketogenic amino acids they can be catabolised for energy in the TCA cycle, or converted to ketone bodies or fatty acids, but they caimot be converted to glucose. 

Figure 23.21. Fates of the Carbon Skeletons of Amino Acids. Glucogenic amino acids are shaded red, and ketogenic amino acids are shaded yellow. Most amino acids are both glucogenic and ketogenic.

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