The document summarizes the metabolic fates of amino acid carbon skeletons after removal of the amino group by transamination or deamination. It states that the carbon skeletons (α-keto acids) can undergo reamination to reform the amino acid or catabolism to form seven intermediates - pyruvate, acetyl CoA, acetoacetyl CoA, fumarate, oxaloacetate, α-ketoglutarate, and succinyl CoA - which then enter pathways to synthesize glucose, lipids, or undergo complete oxidation in the Krebs cycle. It further classifies amino acids based on their degradation products and discusses the metabolic pathways of individual amino acids.

1. Chapter 2
Catabolism of the
Carbon Skeletons of
Amino Acids

2. Metabolic Fate of Amino Acid
Carbon Skeletons
Since, the liver is the major site of nitrogen metabolism in
the body. So, after the removal the amino group (NH2) by
transamination and deamination of amino acids, α-keto
acids (the carbon skeleton) remain and may undergo:
A- Reamination by ammonia (NH3) to form again the
corresponding amino acid by glutamate dehydrogenase.
B- Catabolized to form seven products. pyruvate, acetyl CoA,
acetoacetyl CoA, fumarate, oxaloacetate, α-ketoglutarate
and succinyl CoA.

3. Metabolic Fate of Amino Acid
Carbon Skeletons
Those products enter different pathways which lead to:
1- Synthesis of glycogen or glucose via gluconeogenesis
2- Synthesis of lipid.
3- Complete oxidation (Krebs- cycle) into CO2 and H2O.
Amino acids are classified, beside to essential and
nonessential, into three main groups according to their
degradation products
1. Ketogenic amino acids: are those whose catabolism
gives either acetoacetate,acetoacetyl CoA or acetyl CoA.

4. Metabolic Fate of Amino Acid
Carbon Skeletons
2. Glycogenic Amino Acids: are those whose catabolism
gives pyruvate, or any of the intermediate of krebs cycle,
such as α-ketoglutarate or oxaloacetate.
3. Ketogenic and Glycogenic Amino Acids: are those whose
catabolism gives either glucose or lipid intermediates

5. Metabolic Fate of Amino Acid
Carbon Skeletons
Classification of amino acids as glycogenic and ketogenic

6. A- Amino Acids Forming Pyruvate
1- Conversion of glycine firstly to serine and then to
pyruvate
Glycine is firstly converted to serine and then to pyruvate
by serine hydroxymethyl transferase with the addition of a
methylene group from N5, N10 methylenetetrahydrofolate or
oxidized to CO2 and ammonia

7. 2- Conversion of alanine to
pyruvate
Liver converts alanine to pyruvate by gluconeogenesis in the
case of fasting or deficient amount of glucose by
transamination of alanine and increases urea production.
Also, Alanine is transferred to the circulation by many
tissues, but mainly by muscle.

8. Glucose-Alanine Cycle

9. 3- Serine Forming Pyruvate
In the present of serine dehydratase, serine can be
converted to pyruvate. Also, serine can be converted to
glycine and N5,N10methylenetetrahydrofolate. Glycine can
be oxidized to CO2 and NH3, with the production of N5,N10-
methylenetetrahydrofolate, as was described.

10. 4- Cysteine Forming Pyruvate
Cysteine can be converted to pyruvate via many steps in the
way the sulfhydryl group is released as H2S, SO3
2-, and SCN-

11. 5- Threonine Forming Pyruvate
Mainly, threonine is degraded to β-ketobutyrate by
threonine dehydratase. The β-ketobutyrate is converted to
propionyl CoA and then forming succinyl CoA. The second
pathway involves serine hydroxymethyl transferase yielding
glycine and acetaldehyde(which form acetyl CoA). Then,
glycine is converted to serine in the present of N5,N10-
methylene THF and the same enzyme (serine hydroxymethyl
transferase), which finally is converted to pyruvate. The
products of this reaction are both ketogenic (acetyl-CoA)
and glucogenic (pyruvate).

12. 5- Threonine Forming Pyruvate

13. 6- Tryptophan Forming Pyruvate
Degradation of tryptophan produces alanine and acetyl CoA
. Alanine forms pyruvate as is shown in the Therefore,
tryptophan is both ketogenic (acetyl-CoA) and glucogenic
(pyruvate).

14. B. Amino Acids Forming α- Ketoglutarate
1- Glutamine Forming α- Ketoglutarate
Glutamine (from liver and other tissue) is first converted to
glutamate and ammonia by the enzyme glutaminase which
is an important kidney tubule enzyme (also, it is present in
many other tissues as well). Then glutamate is converted to
α- ketoglutarate, making glutamine a glucogenic amino acid

15. 2- Glutamate Forming α- Ketoglutarate
Glutamate and aspartate are important in collecting and
eliminating amino nitrogen via glutamine synthetase and
the urea cycle, respectively. Glutamate is converted to α-
ketoglutarate by two ways transamination or through
oxidative deamination by glutamate dehydrogenase.

16. 3- Arginine Forming α- Ketoglutarate
Arginine is breaked down to ornithine and urea by arginase
(see urea cycle-Chapter one). Then ornithine undergoes
transamination to yield glutamate- γ-semialdehyde which is
then converted to glutamate and then to α- ketoglutarate.

17. 3- Arginine Forming α- Ketoglutarate

18. 4- Proline Forming α- Ketoglutarate
Catabolism and synthesis processes of proline are a reversal to each
other. Proline is oxidized to open its structure and then is hydrolyzed
forming glutamate-γ-semi-aldehyde.
Like as arginine, glutamate-γ-semialdehyde is converted to glutamate
which then is converted to α-ketoglutarate.

19. 5- Histidine Forming α- Ketoglutarate
Histidine is oxidized and deaminated to urocanic acid by histidase
enzyme. Urocanic acid then is hydrolyzed forming N-
formiminoglutamate (FIGu). Glutamate is released from FIGu after
formimino group is binding to tetrahydrofolate. Then, glutamate is
degraded to α-ketoglutarate. This reaction is used in the diagnosis of
the individuals deficiency of folic acid. So, the increased amount of N-
formimino glutamate (FIGu) in urine indicates the deficiency of folic
acid.

20. C. Amino Acids Forming Oxaloacetate
These amino acids are asparagine and aspartate. Asparagine
is hydrolyzed by asparaginase, which is widely distributed
within the body, where it converts asparagine into ammonia
and aspartate. Aspartate transaminates to oxaloacetate,
after loses its amino group by transamination reaction,
which follows the gluconeogenic pathway to glucose.

21. D. Amino Acids Forming Fumarate and
Acetoacetyl CoA
These are phenylalanine and tyrosine. The first step in the catabolism
of phenylalanine (asessential amino acid) is the hydroxylation to
tyrosine (as non-essential amino acid) by phenylalanine hydroxylase.
Therefore, phenylalanine catabolism always follows the pathway of
tyrosine catabolism. The catabolism of phenylalanine and tyrosine is
forming both fumarate and acetoacetate to be classified as both
glucogenic and ketogenic. Phenylalanine hydroxylase requires
tetrahydro-biopterin as coenzyme which is oxdized to
dihydrobiopterin. Then, dihydro-biopterin reductase with NADPH + H+
or NADH+ H+ is required for regenerating tetrahydrobiopterin. Inborn
errors of phenylalanine and tyrosine metablism lead to the following
diseases : I) Phenylketonuria.
II) Tyrosinemia.
III) Alkaptonuria.
IV) Albinism (see melanin pigments).

22. D. Amino Acids Forming Fumarate and Acetoacetyl CoA

23. D. Amino Acids Forming Fumarate and Acetoacetyl CoA

24. E. Amino Acids Forming Succinyl CoA
Succinyl CoA is formed when methionine, valine, isoleucine,
and threonine are degraded. Methionine is the main methyl
donor in the body forming active methionine in the form of
S-adenosyl- methionine (SAM). SAM is used in many
transmethylation reactions as follows.

25. E. Amino Acids Forming Succinyl CoA
1- Methionine Forming Succinyl CoA
When methionine is converted to α-ketobutrate, it will convert finally
to succinyl CoA. The production of α -ketobutyrate and cysteine via
SAM described . The transulfuration reactions produce cysteine from
homocysteine and serine also produce α -ketobutyrate, the latter
being converted to succinyl-CoA.
If methionine is present in adequate quantities, SAM accumulates and
enhances positively cystathionine synthase, for producing cysteine and
α-ketobutyrate (both are glucogenic)

26. 2- Valine and Isoleucine Forming Succinyl-
CoA
Valine, isoleucine, and leucine, are essential amino acids which are
identified as the branched-chain amino acids, BCAAs. Because the
carbon atoms arrangement of these amino acids cannot be made by
humans, which therefore are an essential element in diet. The
catabolism of these amino acids uses the same enzymes in the first
two steps which is initiated in muscle and yields NADH2 and FADH2 for
generating ATP. The first step in each case is a transamination using a
particular BCAA aminotransferase, with α-ketoglutarate as amine
acceptor. As a result, three different α-keto acids are produced and
oxidized using a common branched-chain α-keto acid dehydrogenase,
yielding the three different CoA derivatives. Subsequently the
metabolic pathways diverge for producing many intermediates.

27. E. Amino Acids Forming Succinyl CoA
2- Valine and Isoleucine Forming Succinyl-CoA

28. E. Amino Acids Forming Succinyl CoA
2- Valine and Isoleucine Forming Succinyl-CoA

29. G. Amino Acids Forming Acetyl CoA and
Acetoacetyl CoA
Leucine is essential branched amino acid. The catabolism of
leucine is similar to that of valine and isoleucine. Leucine is
exclusively ketogenic degraded to acetyl Co and acetoacetyl
CoA (see previous slide).
Lysine is unlike the other amino acids which are transfer
their amino group to α-ketoglutarate in the first step of the
transamination using pyridoxal phosphate as a cofactor
forming glutamate. But lysine transfer their amino group to
α-ketoglutarate forming the metabolite, saccharopine with
out need for the pyridoxal phosphate as a cofactor. that
have been observed in individuals.

30. G. Amino Acids Forming Acetyl CoA and
Acetoacetyl CoA
Saccharopine is immediately hydrolyzed by the enzyme α-aminoadipic
semialdehyde synthase producing α-aminoadipic semialdehyde.
Because this trans-amination reaction is not reversible, lysine is an
essential amino acid. The final end-product of lysine catabolism is
acetoacetyl-CoA (see previous slide). Excretion a large quantities of
lysine and saccharopine in the urine is the indication of the genetic
deficiencies in the enzyme α -aminoadipic semialdehyde synthase that
have been observed in individuals. Other serious disorders is the
failure of the transport of lysine as the other dibasic amino acids
across the intestinal wall cause a deficiencies in protein synthesis.
Also, Transport of fatty acids into the mitochondria for oxidation
require carnitine which lysine is produced.

31. Amino Acid Biosynthesis
1. Biosynthesis of Glutamate/Glutamine and
Aspartate/Asparagine
By simple transamination reactions of α-ketoglutarate and
oxaloacetate, the α-keto acid precursors, glutamate and
aspartate are synthesized. The enzymes required for these
reactions are glutamate dehydrogenase to produce
glutamate, which then can be converted to glutamine by
glutamine synthetase.

32. 1. Biosynthesis of Glutamate/Glutamine and
Aspartate/Asparagine

33. 1. Biosynthesis of Glutamate/Glutamine and
Aspartate/Asparagine

34. 2. Biosynthesis of Alanine
Alanine is non-essential and glucogenic amino acid. It is second
circulating amino acid to glutamine in the blood beside its role in
synthesizing protein. Alanine serves in the
transfer of nitrogen from peripheral tissue to the liver. Specially, it
synthesized in muscle (also by many tissues ) by transamination of
pyruvate and released into blood, in which alanine is formed from
pyruvate at a rate proportional to intracellular pyruvate levels.

35. 3. Biosynthesis of Cysteine
Cysteine is synthesized from the essential amino acid methionine. The reaction is
catalyzed by methionine adenosyltransferase and ATP yields S-adenosyl-methionine
[SAM]. Cystathionine synthase and cystathionase (cystathionine lyase), both use
pyridoxal phosphate as a cofactor, and both are under regulatory control.
Cystathionase is undercontrol by cysteine, as well, cysteine inhibits the expression of
the cystathionine synthase gene. Any genetic defects of these enzymes leads to
homocystinuria (see catabolism of methionine).

36. 4. Biosynthesis of Tyrosine
Hydroxylating the essential amino acid phenylalanine in the cells
(mainly in liver) leads to the production of tyrosine. The relationship
between phenylalanin and tyrosine is just like cysteine and
methionine. Because half of the phenylalanine required goes into the
production of tyrosine; if the diet is rich in tyrosine itself, the
requirements for phenylalanine are reduced by about 50%. But when
phenylalanine in deficiency, tyrosine is became essential.

37. 5. Biosynthesis of Proline
Glutamate is converted into proline by forming glutamate
semialdhyde. Also, the break down of proline produces
glutamate. So, that means proline is formed mainly by the
reversal of its catabolism. Porline and hydroxyproline play a
impotant role in the structure of some proteins as collagen
and elastin.

38. 6. Biosynthesis of Serine
Serine is synthesized from 3-phosphoglycerate (a product of
glycolysis). Dehydrogenase enzyme converts 3-
phosphoglycerate into a keto acid, 3-phosphopyruvate.
Aminotransferase activity with glutamate as a donor for the
amino group produces 3-phosphoserine, which is converted
to serine by phosphoserine phosphatase.

39. 7. Biosynthesis of Glycine
Glycine is involved in many anabolic reactions other than
protein synthesis including the synthesis of purine
nucleotides, heme, glutathione, creatine and serine. The
main pathway to synthesize glycine is from serine by
removal of a hydroxymethyl group (CH2OH) by serine
hydroxymethyl transferase. This reaction involves the
transfer of the hydroxymethyl group from serine to the
cofactor tetrahydrofolate (THF), producing glycine and
N5,N10-methylene-THF. Glycine produced from serine or
from the diet can also be oxidized by glycine cleavage
complex, GCC, to yield a second equivalent of N5,N10-
methylene-tetrahydrofolate as well as ammonia and CO2

40. 7. Biosynthesis of Glycine

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