3. Essential amino acids
• Many amino acids are synthesised by pathways that are present only in
plants and microorganisms.
• Hence, mammals must obtain these amino acids in their diet & are
referred to as essential amino acids.
• The best sources of essential amino acids are animal proteins such as
meat, eggs, and poultry. However, some plant foods, such as the soy
products edamame and tofu, contain all the essential amino acids. This
means they are “complete” sources of protein
• During states of inadequate intake of essential amino acids such as
vomiting or low appetite, clinical symptoms may appear. These
symptoms may include depression, anxiety, insomnia, fatigue, weakness,
growth stunting in the young, etc.
4. Biosynthesis
• Essential amino acids, like nonessential amino acids, are synthesized
from familiar metabolic precursors.
• Their synthetic pathways are present only in microorganisms and plants,
however, and usually involve more steps than non essential amino
acids.
• The enzymes that synthesise essential amino acids were apparently lost
early in animal evolution possibly because of the ready availability of
amino acids in the diet.
5. Biosynthesis
Biosynthesis of aspartate family of amino acids
Aspartate
AT
P
ADP
Aspartokinase
Lysine
NAD⁺ + Pi
NADH
β-aspartate
semialdehyde
dehydrogenase
Homoserine
2 reactions
Threonine
3 reactions
Homocysteine
Methionine
N⁵-methyl
THF
THF
Aspartyl-β-
phosphate
β-aspartate
semialdehyde
8. Catabolism
• The pathways of amino acid catabolism, taken together, normally
account for only 10% to 15% of the human body’s energy production;
these pathways are not nearly as active as glycolysis and fatty acid
oxidation
• The 20 catabolic pathways converge to form 6 major products, all of
which enter the TCA cycle
• From here, the carbon skeletons are diverted to gluconeogenesis or
ketogenesis and are completely oxidised to CO₂ & H₂O
10. Catabolism
Catabolism
Ketogenic amino acids
The seven amino acids that are degraded entirely or in part to
acetoacetyl-CoA and/or acetyl-CoA—phenylalanine, tyrosine, isoleucine,
leucine, tryptophan, threonine, and lysine—can yield ketone bodies in the
liver where acetoacetyl-CoA is converted to acetoacetate and then to
acetone and hydroxybutyrate
Their ability to form ketone bodies is particularly evident in uncontrolled
diabetes mellitus, in which the liver produces large amounts of ketone
bodies from both fatty acids and the ketogenic amino acids.
11. Glucogenic amino acids
The amino acids that are degraded to pyruvate, α-ketoglutarate, succinyl
CoA, fumarate, and/or oxaloacetate can be converted to glucose and
glycogen
Catabolism
The division between ketogenic and glucogenic amino acids is not sharp.
Both ketogenic and glucogenic tryptophan, phenylalanine, threonine,
and isoleucine
Exclusively ketogenic 1. Leucine - very common in proteins. Its
degradation makes a substantial contribution
to ketosis under starvation conditions.
2. Lysine
Exclusively glucogenic
Methionine
12. Uses
Phenylalanine
Our body turns this into neurotransmitters tyrosine, dopamine, epinephrine
& norepinephrine.
It plays an integral role in the structure and function of proteins and
enzymes and the production of other amino acids
Threonine
This is a principal part of structural proteins, such as collagen and elastin, wh
Methionine
It plays an important role in metabolism and detoxification. It’s also necessar
13. Uses
Leucine
Like valine, leucine is a BCAA that is critical for protein synthesis and muscle
Valine
This is one of three branched-chain amino acids (BCAAs). That means it has
It helps stimulate muscle growth and regeneration and is involved in energy p
Isoleucine
The last of the three BCAAs, isoleucine is involved in muscle metabolism and
14. Lysine
plays major roles in protein synthesis, calcium absorption, and the production
Uses
Tryptophan
Often associated with drowsiness, tryptophan is a precursor to serotonin, a n
15. Disorders
Medical condition Approx incidence
(per 100,000
births)
Defective process Defective enzyme Symptoms &
effects
Homocystinuria <0.5 Methionine
degradation
Cystathionine-β-
synthase
Faulty bone
development,
mental retardation
Maple syrup urine
disease (branched
chain ketoaciduria)
<0.4 Isoleucine, leucine
& valine
degradation
Branched chain
keto acid
dehydrogenase
complex
Vomiting,
convulsions,
mental retardation,
early death
Phenylketonuria <8 Conversion of
phenylalanine to
tyrosine
Phenylalanine
hydroxylase
Neonatal vomiting,
Mental retardation
In bacteria, aspartate is the common precursor of lysine, methionine, and threonine
(Fig. 21-32). The biosyntheses of these essential amino acids all begin with the aspartokinase-catalyzed phosphorylation of aspartate to yield aspartyl-𝛃-
phosphate. We have seen that the control of metabolic pathways commonly occurs at the first committed step of the pathway. One might therefore expect Lysine, methionine, and threonine biosynthesis to be controlled as a group. Each of these pathways is, in fact, independently controlled. E. coli has three isozymes of aspartokinase that respond diff erently to the three amino acids in terms both of feedback inhibition of enzyme activity and repression of enzyme synthesis. In addition, the pathway direction is controlled by feedback inhibition at the branch points by the amino acid products of the branches.
Methionine synthase (alternatively, homocysteine methyltransferase) catalyzes the methylation of homocysteine to form methionine using
N5-methyl-THF as its methyl group donor (Reaction 4 ). Methionine synthase is the only coenzyme B12–associated enzyme in mammals besides methylmalonyl CoA mutase (Section 20-2E). However, the coenzyme B12’s Co ion in methionine synthase is axially liganded by a methyl group to form methylcobalamin rather than by a 5′-adenosyl group as in methylmalonyl-CoA mutase (Fig. 20-17). In mammals, the primary function of methionine synthase is not de novo methionine synthesis, as Met is an essential amino acid. Instead, it functions in the cyclic synthesis of SAM for use in biological methylations (Fig. 21-18).
Valine and isoleucine follow the same biosynthetic pathway utilizing pyruvate as a starting reac-
tant, the only diff erence being in the fi rst step of the series. In this thiamine pyrophosphate–dependent reaction, which resembles those catalyzed by pyruvate decarboxylase (Fig. 15-20) and transketolase pyruvate
forms an adduct with TPP that is decarboxylated to hydroxyethyl-TPP. This resonance-stabilized carbanion adds either to the keto group of a second pyruvate to form acetolactate on the way to valine, or to the keto group of 𝛂-ketobutyrate to form 𝛂-aceto-𝛂-hydroxybutyrate on the way to isoleucine. The leucine biosynthetic pathway branches off from the valine pathway. The fi nal step in each of the three pathways, which begin with pyruvate rather than an amino acid, is the PLP-dependent transfer of an amino group from glutamate to form the amino
acid.
The precursors of the aromatic amino acids are the glycolytic intermediate phosphoenolpyruvate (PEP) and erythrose-4-phosphate (an intermediate in the pentose phosphate pathway; Fig. 15-30). Their condensation forms 2-keto-3-deoxy-D-arabinoheptulosonate-7-phosphate . This C7 compound cyclizes and is ultimately converted to chorismate, the branch point for tryptophan synthesis. Chorismate is converted to either anthranilate and then to tryptophan, or to prephenate and on to tyrosine or phenylalanine. Although mammals synthesize tyrosine by the hydroxylation of phenylalanine (Fig. 21-24), many microorganisms synthesize it directly from prephenate. The last step in the synthesis of tyrosine and phenylalanine is the Addition of an amino group through transamination. In tryptophan synthesis, the amino group is part of the serine molecule that is added to indole.
Indole Is Channeled between Two Active Sites in Tryptophan Synthase. The fi nal two reactions of tryptophan biosynthesis are both catalyzed by tryptophan synthase:
1. The α subunit (268 residues) of the α2β2 bifunctional enzyme cleaves indole-3-glycerol phosphate, yielding indole and glyceraldehyde- 3-phosphate.
2. The β subunit (396 residues) joins indole with serine in a PLP-dependent reaction to form tryptophan.
The pathways of amino acid catabolism, taken together, normally account for only 10% to 15% of the human
body’s energy production; these pathways are not nearly as active as glycolysis and fatty acid oxidation. Flux
through these catabolic routes also varies greatly, depending on the balance between requirements for bio synthetic processes and the availability of a particular amino acid. The 20 catabolic pathways converge to form only six major products, all of which enter the citric acid cycle (Fig. 18–15). From here the carbon skeletons are
diverted to gluconeogenesis or ketogenesis or are completely oxidized to CO2 and H2O.
All or part of the carbon skeletons of seven amino acids are ultimately broken down to acetyl-CoA. Five
amino acids are converted to -ketoglutarate, four to succinyl-CoA, two to fumarate, and two to oxaloacetate.
Parts or all of six amino acids are converted to pyruvate, which can be converted to either acetyl-CoA or
oxaloacetate. We later summarize the individual path-ways for the 20 amino acids in flow diagrams, each lead-
ing to a specific point of entry into the citric acid cycle. In these diagrams the carbon atoms that enter the cit-
ric acid cycle are shown in color. Note that some amino acids appear more than once, reflecting different fates
for different parts of their carbon skeletons. Rather than examining every step of every pathway in amino acid
catabolism, we single out for special discussion some enzymatic reactions that are particularly noteworthy for
their mechanisms or their medical significance.
The seven amino acids that are degraded entirely or in part to acetoacetyl-CoA and/or acetyl-CoA—phenylala-
nine, tyrosine, isoleucine, leucine, tryptophan, threonine, and lysine—can yield ketone bodies in the liver, where acetoacetyl-CoA is converted to acetoacetate and then to acetone and -hydroxybutyrate (see Fig. 17–18).
These are the ketogenic amino acids (Fig. 18–15). Their ability to form ketone bodies is particularly evi-
dent in uncontrolled diabetes mellitus, in which the liver produces large amounts of ketone bodies from both fatty acids and the ketogenic amino acids. The amino acids that are degraded to pyruvate, -ketoglutarate, succinyl-CoA, fumarate, and/or oxaloacetate can be converted to glucose and glycogen by pathways. They are the glucogenic amino acids. The division between ketogenic and glucogenic amino acids is not sharp; five
amino acids—tryptophan, phenylalanine, tyrosine, threonine, and isoleucine—are both ketogenic and gluco-
genic. Catabolism of amino acids is particularly critical to the survival of animals with high-protein diets or dur-
ing starvation. Leucine is an exclusively ketogenic amino acid that is very common in proteins. Its degradation makes a substantial contribution to ketosis under starvation conditions.
Notice that five of the amino acids are both glucogenic and ketogenic. The amino acids degraded to pyruvate are also potentially ketogenic. Only two amino acids, leucine and lysine, are exclusively ketogenic.
