Amino Acid Catabolism: Carbon Skeletons

Degradation exceeds demand for new protein When: AMINO ACID CATABOLISM          Accounts for ~ 10% of energy requirement of adults        Degradation exceeds demand for new protein When:  There is excess protein in diet (amino acids are not stored) and also during starvation when carbohydrates are not available.       

After removing of amino group the carbon skeletons of amino acids are transformed into metabolic intermediates that can be converted into glucose, fatty acids (acetyl CoA), ketone bodies or oxidized by the citric acid cycle.

Amino Acid Carbon Skeletons Amino acids are grouped into 2 classes, based on whether or not their carbon skeletons can be converted to glucose: glucogenic ketogenic.

Also source of carbons for gluconeogenesis in liver   Glucogenic vs Ketogenic amino acids          GLUCOGENIC: are degraded to pyruvate or a member of the TCA cycle (succinylCoA, OAA, a-ketoglutarate, fumarate). In absence of carbohydrates, glucogenic amino acids permit continued oxidation of fatty acids by maintaining TCA cycle intermediates. Also source of carbons for gluconeogenesis in liver - phe, ile, tyr, trp ( pitt )    

Carbon skeletons of glucogenic amino acids are degraded to: pyruvate, or a 4-C or 5-C intermediate of Krebs Cycle. (succinylCoA, OAA, a-ketoglutarate, fumarate). These are precursors for gluconeogenesis. Glucogenic amino acids are the major carbon source for gluconeogenesis when glucose levels are low. They can also be catabolized for energy, or converted to glycogen or fatty acids for energy storage.

  Glucogenic vs Ketogenic amino acids      KETOGENIC: yield ketone bodies ( AcetylCoA or AcetoAcetate as end products of catabolism ---- leu, lys  GLUCOGENIC AND KETOGENIC: yield both ketogenic and glucogenic products. - all others

Carbon skeletons of ketogenic amino acids are degraded to: acetyl-CoA, or acetoacetate. Acetyl CoA, & its precursor acetoacetate, cannot yield net production of oxaloacetate, the gluconeogenesis precursor. Carbon skeletons of ketogenic amino acids can be catabolized for energy in Krebs Cycle, or converted to ketone bodies or fatty acids. THEY CANNOT BE CONVERTED TO GLUCOSE.

The strategy of amino acid degradation is to transform the carbon skeletons into major metabolic intermediates that can be converted into glucose, or oxidized by the citric acid cycle. The carbon skeletons of a diverse set of 20 amino acids are funneled into only 7 molecules: pyruvate, acetyl CoA, acetoacetylCoA, ketoglutarate, succinyl CoA, fumarate and oxaloacetate. .

Catabolism of C-skeletons of Amino Acids The carbon skeletons of amino acids can be used for energy storage and/or energy. Some can be used to synthesize glucose and are termed glucogenic. Glucogenic amino acids are converted to either pyruvate or some intermediate of the Krebs (citric acid) cycle – remember that gluconeogenesis begins with oxaloacetate, a component of the Krebs cycle. Anything that feeds into an intermediate of the cycle, or that can be used to synthesize an intermediate (importantly, this includes pyruvate, which can form oxaloacetate via the pyruvate carboxylase route) can be used by liver to synthesize new glucose.

Catabolism of C-skeletons of Amino Acids The carbon skeletons of amino acids can be used for energy storage and/or energy. Some can be used to synthesize glucose and are termed glucogenic. while some are converted to acetylCoA (ketogenic amino acids) these CANNOT be used to synthesize glucose. Ketogenic amino acids can be converted to fatty acids for storage as triglyceride and later oxidation (fed state), or to ketone bodies (made in liver mitochondria; mostly during fasting) for oxidation by a number of tissues, importantly including brain. Ketogenic amino acids can also be used by the liver to synthesize cholesterol

Catabolism of C-skeletons of Amino Acids This is the general overall idea of catabolism – you will not need to know the detailed pathways for individual amino acids, but should have a good overall idea of the general scheme of things.