Download 1. What happens during the digestion of proteins, and what are the

Chapter 28: Protein and Amino Acid Metabolism
1.!
What happens during the digestion of proteins, and what are the fates of the
amino acids? Be able to list the sequence of events in the digestion of proteins, and
describe the nature of the amino acid pool.!
2.!
What are the major strategies in the catabolism of amino acids? Be able to
identify the major reactions and products of amino acid catabolism and the fate of the
products.!
3.!
What is the urea cycle? Be able to list the major reactants and products of the urea
cycle.!
4.!
What are the essential and nonessential amino acids, and how, in general, are
amino acids synthesized? Be able to define essential and nonessential amino acids,
and describe the general strategy of amino acid biosynthesis.
Chapter 28: Protein and Amino Acid Metabolism
1.!
What happens during the digestion of proteins, and what are the fates of the
amino acids?
The goal of protein digestion is the hydrolysis of all peptide bonds to produce free amino
acids.
No chemical digestion of protein occurs in the mouth, but large pieces of food are converted
into smaller, more digestible portions there.
HCl in the stomach (pH 1–2) denatures dietary protein.
Gastric secretions also include pepsinogen , a zymogen that is activated by acid to give
the enzyme pepsin.
Pepsin is stable and active at pH 1–2, it hydrolyzes some of the peptide bonds in the
denatured proteins, which are broken down into smaller polypeptides.
Chapter 28: Protein and Amino Acid Metabolism
The polypeptides produced by pepsin then enter the small intestine, where the pH is about
7–8.
Pepsin is inactivated in the less acidic environment, and a group of pancreatic zymogens is
secreted. The activated enzymes (proteases such as trypsin , chymotrypsin , and
carboxypeptidase ) then take over further hydrolysis of peptide bonds in the partially
digested proteins.
The combined action of the pancreatic proteases in the small intestine and other proteases
in the cells of the intestinal lining frees the amino acids from dietary proteins. After
active transport across cell membranes lining the intestine, the amino acids are
absorbed directly into the bloodstream.
Amino acid pool: The entire collection of free amino acids in the body.
Amino acids are continuously entering the pool, not only from digestion but also from the
breakdown of old protein, and are continuously being withdrawn for synthesis of new
nitrogen-containing biomolecules .
2.!
What are the major strategies in the catabolism of amino acids?
Chapter 28: Protein and Amino Acid Metabolism
When not incorporated into new proteins, each of the 20 amino acids is degraded via its
own unique pathway. The general scheme for amino acid catabolism is the same for
each one:
Removal of the amino group
Use of nitrogen in synthesis of new nitrogen compounds
Passage of nitrogen into the urea cycle
Incorporation of the carbon atoms into compounds that can enter the citric acid cycle
Our bodies do not store nitrogen-containing compounds and ammonia is toxic to cells.
Amino nitrogen must either be incorporated into urea and excreted, or be used in the
synthesis of new nitrogen-containing compounds such as:
Nitric oxide
Hormones
Neurotransmitters
Nicotinamide (in NAD+ and NADP+ )
Heme (in red blood cells)
Purine and pyrimidine bases (for nucleic acids)
Once the amino acid carbon skeletons have been converted into compounds that can enter
the citric acid cycle, the generation of energy, fats, glucose, or ketone bodies can
commence depending on the current needs of the body.
The first step in amino acid catabolism is removal of the amino group.
In this process, known as transamination , the amino group of the amino acid and the keto
group of an ! - keto acid change places:
Most transaminase enzymes are specific for ! - ketoglutarate as the amino group acceptor
and work with several amino acids.
The ! - ketoglutarate is converted to glutamate, and the amino acid is converted to an ! keto acid.
Chapter 28: Protein and Amino Acid Metabolism
The glutamate from transamination serves as an amino group carrier.
Glutamate can be used to provide amino groups for the synthesis of new amino acids, but
most of the glutamate formed in this way is recycled to regenerate ! - ketoglutarate .
This process, known as oxidative deamination , oxidatively removes the glutamate amino
group as ammonium ion to give back ! - ketoglutarate .
Transamination interconverts amino acid amino groups and carbonyl groups as necessary.
The transamination reactions are reversible and go easily in either direction, depending on
the concentrations of the reactants.
In this way, amino acid concentrations are regulated by keeping synthesis and breakdown in
balance.
3.!
What is the urea cycle?
The ammonium ion formed in this reaction proceeds to the urea cycle where it is eliminated
in the urine as urea.
Chapter 28: Protein and Amino Acid Metabolism
Excretion of ammonia in urine is not feasible for mammals, because the volume of water
needed to accomplish this safely would cause dehydration. Mammals must first
convert ammonia, in solution as ammonium ion, to nontoxic urea via the urea cycle.
Urea formation begins with an energy investment, Ammonium ion, bicarbonate ion, and ATP
combine to form carbamoyl phosphate.
Step 1 of the urea cycle transfers the carbamoyl group, from carbamoyl phosphate to
ornithine , an amino acid not found in proteins, to give citrulline , another nonprotein
amino acid. This exergonic reaction introduces the first urea nitrogen into the urea
cycle.
Step 2 , a molecule of aspartate combines with citrulline in a reaction driven by conversion
of ATP to AMP and pyrophosphate followed by the additional exergonic hydrolysis of
Chapter 28: Protein and Amino Acid Metabolism
pyrophosphate. Both nitrogen atoms destined for elimination as urea are now bonded
to the same carbon atom in argininosuccinate .
Step 3 cleaves argininosuccinate into two pieces:
arginine, an amino acid
fumarate, an intermediate in the citric acid cycle
Step 4 , is hydrolysis of arginine to give urea and regenerate the reactant in Step 1 of the
cycle, ornithine .
Hereditary diseases associated with defects in the enzymes for each step in the urea cycle
have been identified. The resulting abnormally high levels of ammonia in the blood
( hyperammonemia ) cause vomiting in infancy, lethargy, irregular muscle coordination
(ataxia), and mental retardation.
In summary, the urea cycle:
Eliminates C from CO2, N from NH4+ , and N from the amino acid aspartate as urea.
Breaks four high-energy phosphate bonds.
Produces the citric acid cycle intermediate, fumarate.
Chapter 28: Protein and Amino Acid Metabolism
All amino acid carbon skeletons can be used to generate energy.
Amino acids converted to acetoacetyl-SCoA or acetyl- SCoA that enters the ketogenesis
pathway are called ketogenic amino acids.
Amino acids that proceed by way of oxaloacetate to the gluconeogenesis pathway are
known as glucogenic amino acids.
Both ketogenic and glucogenic amino acids are able to enter fatty acid biosynthesis via
acetyl- SCoA .
Chapter 28: Protein and Amino Acid Metabolism
Ketogenic amino acids are shown in pink boxes.
Glucogenic amino acids are shown in blue boxes.
Chapter 28: Protein and Amino Acid Metabolism
4.!
What are the essential and nonessential amino acids, and how, in general, are
amino acids synthesized?
Nonessential amino acid: One of 11 amino acids that are synthesized in the body and are
therefore not necessary in the diet.
Essential amino acid: An amino acid that cannot be synthesized by the body and thus
must be obtained in the diet.
Meats contain all of the essential amino acids. The foods that do not have all of them are
described as having incomplete amino acids.
Food combinations that together contain all of the amino acids are complementary
sources of protein.
Inability to make essential amino acids is efficient.
We synthesize nonessential amino acids in 1–3 steps. Synthesis of the essential amino
acids by other organisms is much more complicated, requiring many more steps and a
big energy investment.
Four common metabolic intermediates, which play many other roles, are the precursors for
synthesis of the nonessential amino acids, no excess inventory.
Chapter 28: Protein and Amino Acid Metabolism
Nonessential amino acids derive their amino groups from glutamate. This is the molecule
that carries ammonia into the urea cycle.
Glutamate can also be made from ! - ketoglutarate and NH4+ by reductive amination ,
the reverse of oxidative deamination . The same glutamate dehydrogenate enzyme
carries out the reaction.
Glutamate also provides N for the synthesis of other N-containing compounds, including the
purines and pyrimidines that are part of DNA.
Glutamine is made from glutamate and asparagine is made by reaction of glutamine with
aspartate :
Tyrosine is synthesized from phenylalanine, so it is classified as a nonessential amino acid.
Several metabolic diseases are associated with defects in the enzymes needed to convert
phenylalanine to tyrosine and other metabolites. The best known of these diseases is
phenylketonuria (PKU). In 1947 it was found that failure to convert phenylalanine to
tyrosine causes PKU.