Amino acids function as monomers of polypeptides. Energy metabolites. Precursors for nitrogen-containing compounds (heme, glutathione, nucleotides, coenzymes) Amino acids are classified into 2 groups: essential and nonessential Mammals can synthesize nonessential amino acids from metabolic precursors. Essential amino acids must be taken in from diet. Excess dietary amino acids are converted to common metabolic intermediates: pyruvate, OAA, acetyl-CoA, and -ketoglutarate.

1. Chapter 5
Breakdown
Proteins to Amino Acids, Starch to Glucose
Synthesis
Amino Acids to Proteins, Glucose to Starch

2. Amino acid metabolism
• Amino acids function as monomers of polypeptides.
• Energy metabolites.
• Precursors for nitrogen-containing compounds (heme,
glutathione, nucleotides, coenzymes)
• Amino acids are classified into 2 groups: essential and
nonessential
• Mammals can synthesize nonessential amino acids from
metabolic precursors.
• Essential amino acids must be taken in from diet.
• Excess dietary amino acids are converted to common
metabolic intermediates: pyruvate, OAA, acetyl-CoA, and -
ketoglutarate.

3. What Are Amino Acids?
• Building blocks of proteins
– Body uses 20 different amino acids to make proteins
• 9 of the 20 amino acids must be consumed in the diet (essential
amino acids; EAA)
– Body cannot make them on its own
• Other 11 amino acids are not essential (NEAA)
– Can be made from other amino acids in the diet
• Some NEAAs can become EAAs under certain conditions
– Infants have different needs for growth
– Defects in amino acid metabolism
• Tyrosine can become essential in individuals with phenylketonuria (PKU), an inborn
error
of phenylalanine metabolism
Leucine Tryptophan Methionine
Isoleucine Threonine Lysine
Valine Histidine Phenylalanine
Berg JM, et al. Biochemistry. 5th ed. New York, NY: WH Freeman & Co.; 2002.
3

4. Basic Structure of an Amino Acid
• Central carbon atom (alpha carbon [Cα]) linked to
– Amino group (positive)
– Carboxylic acid group (negative)
– Hydrogen
– Distinctive side chain (R)
• Makes each AA different
Berg JM, et al. Biochemistry. 5th ed. New York, NY: WH Freeman & Co.; 2002.
4
+
–

5. OVERVIEW OF AMINO ACID METABOLISM
ENVIRONMENT ORGANISM
Ingested
protein
Bio-
synthesis
Protein
AMINO
ACIDS
Nitrogen
Carbon
skeletons
Urea
Degradation
(required)
1
2 3
a
b
Purines
Pyrimidines
Porphyrins
c c
Used for
energy pyruvate
α-ketoglutarate
succinyl-CoA
fumarate
oxaloacetate
acetoacetate
acetyl CoA
(glucogenic)
(ketogenic)

6. Amino Acid Requirements of Humans
--------------------------------------------------------------------
Nutritionally Essential Nutritionally Nonessential
--------------------------------------------------------------------
Argininea
Alanine
Histidine Asparagine
Isoleucine Aspartate
Leucine Cysteine
Lysine Glutamate
Methionine Glutamine
Phenylalanine Glycine
Threonine Proline
Tryptophan Serine
Valine Tyrosine
---------------------------------------------------------------------
a “
Nutritionally semiessential.” Synthesized at rates
inadequate to support growth of children.

7. Synthesis of proteins
Fates of amino acids
Sources of amino acids
§ 3.1 The sources and fates of AAs
A m in o a c id
m etab o lic p o o l
N H 3
α-K eto ac id
K eto n e b o d ies
O x id a tio n
G lu c o s e
U rea
A m in e
C O 2
c o n v ers io n
N o n - p ro tein n itro g en
c o m p o u n d s
d eg rad a tio n
s y n th es is
D ietary
p ro tein s
T is s u e
p ro tein s
A m in o a c id s
s y n th es iz ed

8. NITROGEN BALANCE
Nitrogen balance = nitrogen ingested - nitrogen excreted
(primarily as protein) (primarily as urea)
Nitrogen balance = 0 (nitrogen equilibrium)
protein synthesis = protein degradation
Positive nitrogen balance
protein synthesis > protein degradation
Negative nitrogen balance
protein synthesis < protein degradation

9. FATE OF THE CARBON SKELETONS
Carbon skeletons are used for
energy.
Glucogenic: TCA cycle intermediates
or pyruvate (gluconeogensis)
Ketogenic: acetyl CoA, acetoacetyl CoA,
or acetoacetate

10. Glucogenic vs ketogenic amino acids
· ketogenic: yield AcCoA or AcAc as end products of
catabolism
- leu, lys
· glucogenic: are degraded to pyruvate or a member of the
TCA cycle (succinylCoA, OAA, -ketoglutarate, fumarate).
In absence of sugars, glucogenic amino acids permit
continued oxidation of fatty acids by maintaining TCA
cycle intermediates.
Also source of carbons for gluconeogenesis in liver
- ile, phe, tyr, trp
· glucogenic and ketogenic: yield both ketogenic and
glucogenic products.
- all others

11. Protein Turnover
• There is a constant flux between making new muscle
protein and breaking down old muscle protein
– Known as “protein turnover”
• Goal for increasing muscle size is for muscle protein
synthesis to exceed breakdown
Phillips SM, et al. J Am Coll Nutr. 2009;28(4):343-354.
Muscle
synthesis
Muscle
protein
Muscle
breakdown
Amino
acids
Amino acids
Blood
11

12. Amino Acid Metabolism in Muscle
• Six amino acids can be metabolized by muscle
– Alanine
– Aspartate
– Glutamate
– BCAA

13. Metabolic Functions of the Liver
Hepatocytes are metabolic super
achievers in the body. They play
critical roles in synthesizing molecules
that are utilized elsewhere to support
homeostasis, in converting molecules
of one type to another, and in
regulating energy balances.

14. Protein Metabolism
The most critical aspects of protein metabolism that
occur in the liver are:
•Deamination and transamination of amino acids,
followed by conversion of the non-nitrogenous part
of those molecules to glucose or lipids.
• Several of the enzymes used in these pathways (for
example, alanine and aspartate aminotransferases)
are commonly assayed in serum
• to assess liver damage.

15. •Removal of ammonia from the body by synthesis of urea.
Ammonia is very toxic and if not rapidly and efficiently
•removed from the circulation, will result in central nervous
system disease. A frequent cause of such hepatic
encephalopathy in
•dogs and cats are malformations of the blood supply to
the liver called portosystemic shunts.
•Synthesis of non-essential amino acids.

16. •Hepatocytes are responsible for synthesis
of most of the plasma proteins. Albumin, the
major plasma protein,
• is synthesized almost exclusively by the
liver. Also, the liver synthesizes many of the
clotting factors necessary for blood
coagulation.

17. Breakdown of amino acids
• 3 stages
1. Deamination-the removal of the amino group- conversion to
ammonia or the amino group of asp.
2. Incorporation of ammonia and aspartate nitrogen atoms into
urea to be exreted.
3. Conversion of -keto acids into common metabolic
intermediates.
Most reactions similar to those covered in other pathways.
The first step is deamination of the amino acid.

18. N catabolism
General strategy:
 removal of N from amino acid by transamination (generally
first or second step of amino acid catabolic pathways) and
 collection of N in glutamic acid
 deamination of glutamic acid with release of NH4
+
-glutamate dehydrogenase
3. Collection of N in glutamine or alanine for delivery to liver
 removal of NH4
+ by : i. secretion; or ii. conversion to
urea or other less toxic form.
2
1
4

19. Deamination
• Most amino acids use a transamination to deminate the amino acids.
• This transfers the amino group of an a-keto acid to make a new amino
acids in reactions catalyzed by aminotransferases (aka transaminases).
• -ketoglutarate is the predominant amino group acceptor (produces
glutamate).
Amino acid + -ketoglutarate -ketoacid + glutamate
Glutamate’s amino group is then transferred to oxaloacetate to make asp
Glutamate + OAA -ketoglutarate + aspartate
• Glutamate dehydrogenase (GDH) main catalyst for deamination.
Glutamate + NAD(P)+ + H2O -ketoglutarate + NH4
+ + NAD(P)H

20. Transamination
• Aminotransferase reactions occur in 2 stages:
1. The amino group of an amino acid is transferred to the enzyme:
Amino acid + enzyme -keto acid + enzyme-NH2
2. The amino group is transferred to the keto acid acceptor, -ketoglutarate
to form glutamate and regenerate the enzyme.
-ketoglutarate + enzyme-NH2 enzyme + glutamate
• Aminotransferases require the aldehyde-containing coenzyme, pyridoxal-
5’-phosphate (PLP) a derivative of pyridoxine (aka vitamin B6).
• PLP is attached to the enzyme via a Schiff base linkage by condensation
of the aldehyde group to thee -amino group of a Lys within the enzyme.
• PLP is converted to pyridoxamine-5’-phosphate (PMP)

21. Figure 26-1ab Forms of pyridoxal-5¢-phosphate.
(a) Pyridoxine (vitamin B6) and (b) Pyridoxal-5¢-phosphate (PLP).
Page
986

22. Figure 26-1cd Forms of pyridoxal-5¢-phosphate.
(c) Pyridoxamine-5¢-phosphate (PMP) and (d) The Schiff base
that forms between PLP and an enzyme -amino group.
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986

23. Transamination
• Can be reversed to convert an -keto acid to an amino acid
• PLP functions as an electron sink.
• Cleavage of any of the amino acid C atom’s 3 bonds produces a
resonance stabilized structure.
• PLP can therefore be used in both transamination and decarboxylation
reactions.
• Most aminotransferases accept only -ketoglutarate or oxaloacetate as
the -keto acid substrate in the second stage of the reaction (reverse
reaction).
• The amino groups of most amino acids are therefore incorporated in the
formation of glutamate or aspartate.
• Glu and Asp are connected by glutamate-aspartate aminotransferase.
Glutamate + oxaloacetate -ketoglutarate + aspartate
• Oxidative deamination of glutamate regenerates -ketoglutarate and
makes ammonia.
• Ammonia and aspartate are the amino donors for urea synthesis.

24. Figure 26-3 The glucose–alanine
cycle.
Page
988

25. Oxidative demaniation
• Glutamate
dehydrogenase (GDH)
can use either NAD+
or NADP+ as redox
coenzyme.
• Allosterically inhibited
by GTP and NADH.
• Activated by ADP, Leu,
and NAD+.

26. Other deamination pathways
• Gln made from glutamate and ammonia by glutamine
synthestase. N can be transported to the liver from Gln.
• Ammonia is released for urea production in the liver
mitochondria or for excretion after processing by
glutiminase.

27. Other deamination pathways
• Gln made from glutamate and ammonia by glutamine
synthestase. N can be transported to the liver from Gln.
• Ammonia is released for urea production in the liver
mitochondria or for excretion after processing by
glutiminase.

28. Other deamination pathways
• Gln made from glutamate and ammonia by glutamine
synthestase. N can be transported to the liver from Gln.
• Ammonia is released for urea production in the liver
mitochondria or for excretion after processing by
glutiminase.

29. Oxidative demaniation
• Glutamate
dehydrogenase (GDH)
can use either NAD+
or NADP+ as redox
coenzyme.
• Allosterically inhibited
by GTP and NADH.
• Activated by ADP, Leu,
and NAD+.