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Metabolism
F. Ferdinal
• This obviously means that proteins are the key molecules in the
processes of life, and it is now known that virtually all the activities which
sustain living organisms are carried out by proteins.
• Proteins are constructed on a simple pattern, but that pattern allows for
an almost endless diversity of structure and function.
• All proteins, whether from the most ancient lines of bacteria or from the most
complex forms of life, are constructed from the same set of 20 amino acids,
covalently linked in characteristic linear sequences.
• Proteins (from Greek πρωτείνη - proteios - very important, 1838), are :
Biopolymers that consist of linear chains of amino acid residues.
• All organism use the same 20 amino acids as buildig blocks for the assembly
protein molecules. These 20 amino acids are therefore often cited as the common
or standard amino acids.
• DespiteFEBS*.ppt limited number of amino acid types, the variations in the order in
which
they are are connected and in the number of amino acids per protein, allow an
almost limetless variety of proteins.
Formation of cystine
D. Side Chains with Alcohol Groups
E. Basic R Groups
• Aspartate (Asp, D) and glutamate (Glu, E) are dicarboxylic amino acids and have
negatively charged hydrophilic side chains at pH 7.
• Asparagine (Asn, N) and glutamine (Gln, Q) are the amides of aspartic acid and
glutamic acid, respectively. Although the side chains of asparagine and glutamine
are uncharged, these amino acids are highly polar and are often found on the
surfaces of proteins, where they can interact with water molecules.
Amino Acid Groups
Other Amino Acids and Amino Acid Derivatives
More than 200 different amino acids are found in living organisms. In addition to the standard
amino acids that are incorporated into proteins, all species contain a variety of L-amino acids
that are either precursors of the common amino acids or intermediates in other biochemical
pathways.
Examples are : homocysteine,
homoserine,
ornithine, and
citrulline .
S-Adenosylmethionine (SAM) is a common methyl donor in many
biochemical pathways .
Bacteria and fungi synthesize D-amino acids that are used in cell walls and in
complex peptide antibiotics such as actinomycin D.
Several common amino acids are chemically modified to produce biologically important
amines. These are synthesized by enzyme-catalyzed reactions that include decarboxylation
and deamination.
The 22nd amino acid is Pyrrolysine ( Pyl or O), found in some species of archaebacteria
(2003). Pyrrolysine is a modified form of lysine that is synthesized before being added to a
growing polypeptide chain by the translation machinery.
Selenocysteine and Pyrrolysine have their own codons, UGA and UAG, respectively, which
is why they are considered as standard amino acids
V Valine
F Phenylalanine
W Tryptophan
I Isoleucine
T Threonine
H Histidine
M Methionine
L Leucine
K Lysine
21
Stereochemistry of amino acids
The a-helix
• Hydrolysis by 6 M HCl
• Hydrolysis with phenylisothiocyanate (PITC) at pH 9.0
49
Isoelectric Points
• In acidic solution, the carboxylate and amine are in their
conjugate acid forms, an overall cation
• In basic solution, the groups are in their base forms, an
overall anion
• In neutral solution cation and anion forms are present
• This pH where the overall charge is 0 is the isoelectric
point, pI
50
Prentice Hall c2002 Chapter 3 51
Prentice Hall c2002 Chapter 3 52
AMINO ACID METABOLISM
The Nitrogen Cycle and Nitrogen Fixation
Assimilation of Ammonia
Biosynthesis of serine
Biosynthesis of glycine
Biosynthesis of cysteine from serine in many bacteria and plants.
Anthranilate.
Synthesis of histidine from phosphoribosyl pyrophosphate (PRPP) and ATP. Histidine is derived
from PRPP (5 C atoms), the purine ring of ATP (1 N and 1 C), glutamine (1 N), and
glutamate (1 N).
Amino Acids as Metabolic Precursors
• Glu and Asp, are amino group donors in many transamination reactions and
required in the urea cycle.
• Gln and Asp are also required as precursors in both purine and pyrimidine
biosynthesis.
• Their half-lives can vary from a few minutes to several weeks but the half-
life of a given protein in different organs and species is generally similar.
1. During the normal synthesis and degradation of cellular proteins (protein turnover),
some amino acids that are released from protein breakdown and are not needed for
new protein synthesis undergo oxidative degradation.
2. When a diet is rich in protein and the ingested amino acids exceed the body’s needs
for protein synthesis, the surplus is catabolized; amino acids cannot be stored.
83
pI Depends on Side Chain
• The 15 amino acids thiol, hydroxyl groups or pure
hydrocarbon side chains have pI = 5.0 to 6.5 (average of
the pKa’s)
• D and E have acidic side chains and a lower pI
• H, R, K have basic side chains and higher pI
84
Electrophoresis
• Proteins have an overall pI that depends on the net
acidity/basicity of the side chains
• The differences in pI can be used for separating proteins
on a solid phase permeated with liquid
• Different amino acids migrate at different rates,
depending on their isoelectric points and on the pH of the
aqueous buffer
85
Amino Acid Catabolism
• Amino acids obtained from the degradation of endogenous proteins or from the
diet can be used for the biosynthesis of new proteins.
• Amino acids not needed for the synthesis of proteins are catabolized in order to
make use of their nitrogen and their carbon skeletons.
• The first step in amino acid degradation is often removal of the group. Next, the
carbon chains are altered in specific ways for entry into the central pathways of
carbon metabolism.
• Removal of the group of an amino acid occurs in several ways. The amino acid
usually undergoes transamination with α--ketoglutarateto form an acid and
glutamate.
• The net effect of these two reactions is the release of groups as ammonia and
the formation of NADH and α-keto acids:
Overview of amino acid catabolism in mammals. The amino groups and
the carbon skeleton take separate but interconnected pathways.
Conversion of the carbon skeletons of amino acids to pyruvate, acetoacetate, acetyl
CoA, orcitric acid cycle intermediates for further catabolism.
B. Arginine, Histidine, and Proline
C. Glycine and Serine
D. Threonine
E. The Branched-Chain Amino Acids
F. Methionine
G. Cysteine
• Discovered by Hans Krebs and Kurt Henseleit in 1932, (almost exclusively in liver).
• The second nitrogen atom destined for urea comes from aspartate and is
incorporated when citrulline condenses with aspartate to form argininosuccinate.
• Final reaction of the urea cycle, the guanidinium group of arginine is hydrolytically
cleaved to form ornithine and urea in a reaction catalyzed by arginase.
The urea cycle.
• The exchange of glucose and alanine between muscle and liver, called the
glucose–alanine cycle , provides an indirect means for muscle to eliminate nitrogen
and replenish its energy supply.
Glucose–alanine cycle
Renal Glutamine Metabolism Produces Bicarbonate
• The body often produces acids as metabolic end products; the resulting anions are
eliminated in the urine and the protons remain in the body.
• The blood has an effective buffer system for the protons, they react with bicarbonate.
to produce which is eliminated by the lungs (Fig). While this system effectively
neutralizes the excess hydrogen ions, it does so at the cost of depleting blood
bicarbonate. Bicarbonate is replenished by glutamine catabolism in the kidneys.
• Pathways for the biosynthesis of the carbon skeletons of amino acids begin with
simple metabolic precursors such as pyruvate and citric acid cycle intermediates.
• Nonessential amino acids are those that animals can produce in quantities that are
sufficient for growth. These amino acids are generally formed by short, energetically
inexpensive pathways. Essential amino acids must be supplied
in the diets of animals; these amino acids are synthesized by bacteria and plants.
• Amino acids obtained from protein degradation or directly from food can be
catabolized. Catabolism begins with deamination, followed by modification of the
remaining carbon chains for entry into the central pathways of carbon metabolism.
• The pathways for the degradation of amino acids lead to pyruvate, acetyl CoA, or
intermediates of the citric acid cycle. Amino acids that are degraded to citric acid
cycle intermediates are glucogenic. Those that form acetyl CoA are ketogenic.
• In mammals, most nitrogen is excreted as urea, which is formed by the urea cycle in
the liver. The carbon atom of urea is derived from bicarbonate. One amino group is
derived from ammonia, and the other from aspartate.