Download 28.1 Digestion of Protein

28.1 Digestion of Protein
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
1
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
2
28.2 Amino Acid Metabolism: An
Overview
• 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continuously being withdrawn for synthesis of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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
3
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
4
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
5
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
6
28.3 Amino Acid Catabolism: The Amino Group
• 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 aketo acid change places:
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
7
• Most transaminase enzymes are specific for aketoglutarate as the amino group acceptor and work
with several amino acids.
• The a-ketoglutarate is converted to glutamate, and the
amino acid is converted to an a-keto acid.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
8
• 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 a-ketoglutarate.
• This process, known as oxidative deamination, oxidatively
removes the glutamate amino group as ammonium ion to give
back a-ketoglutarate.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
9
• 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.
• The ammonium ion formed in this
reaction proceeds to the urea cycle
where it is eliminated in the urine as
urea.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
10
28.4 The Urea cycle
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
11
• 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 pyrophosphate.
Both nitrogen atoms destined for elimination as
urea are now bonded to the same carbon atom in
argininosuccinate.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
12
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
13
• 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
14
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
15
28.5 Amino Acid Catabolism: The
Carbon Atoms
• All amino acid carbon skeletons can be
used to generate energy.
• Amino acids converted to acetoacetylSCoA 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.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
16
• Ketogenic amino acids are shown in pink boxes.
• Glucogenic amino acids are shown in blue boxes.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty Eight
17