Download 4.Lect Carbon skeleton intro

Amino Acid Catabolism: Carbon
Skeletons
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.
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.