1. Stoichiometry and Energy Cost of CO2 Assimilation
Fixation of three CO2 molecules yields one glyceraldehyde 3-phosphate
Nine ATP molecules and six NADPH molecules are consumed

2. FIGURE 20-14 Stoichiometry of CO2 assimilation in the Calvin cycle
FIGURE Stoichiometry of CO2 assimilation in the Calvin cycle. For every three CO2 molecules fixed, one molecule of triose phosphate (glyceraldehyde 3-phosphate) is produced and nine ATP and six NADPH are consumed. 2

3. Photosynthesis: From Light and CO2 to Glyceraldehyde 3-phosphate
The photosynthesis of one molecule of glyceraldehyde 3-phosphate requires the capture of roughly 24 photons

4. ATP and NADPH produced by the light reactions are essential substrates for the reduction of CO2
FIGURE Source of ATP and NADPH. ATP and NADPH produced by the light reactions are essential substrates for the reduction of CO2. The photosynthetic reactions that produce ATP and NADPH are accompanied by movement of protons (red) from the stroma into the thylakoid, creating alkaline conditions in the stroma. Magnesium ions pass from the thylakoid into the stroma, increasing the stromal [Mg2+]. 4

5. Enzymes in the Calvin Cycle are Regulated by Light
Target enzymes are
ribulose 5-phosphate kinase,
fructose 1,6-bisphosphatase,
seduloheptose 1,7-bisphosphatase, and
glyceraldehyde 3-phosphate dehydrogenase

6. Light activation of several enzymes of the Calvin cycle
FIGURE Light activation of several enzymes of the Calvin cycle. The light activation is mediated by thioredoxin, a small, disulfidecontaining protein. In the light, thioredoxin is reduced by electrons moving from photosystem I through ferredoxin (Fd) (blue arrows), then thioredoxin reduces critical disulfide bonds in each of the enzymes sedoheptulose 1,7-bisphosphatase, fructose 1,6-bisphosphatase, ribulose 5-phosphate kinase, and glyceraldehyde 3-phosphate dehydrogenase, activating these enzymes. In the dark, the —SH groups undergo reoxidation to disulfides, inactivating the enzymes.
Light activation of several enzymes of the Calvin cycle 6

7. Photorespiration
So far, we saw that plants oxidize water to O2 and reduce CO2 to carbohydrates during the photosynthesis
Plants also have mitochondria where usual respiration with consumption of O2 occurs in the dark
In addition, a wasteful side reaction catalyzed by Rubisco occurs in mitochondria
This reaction consumes oxygen and is called photorespiration; unlike mitochondrial respiration, this process does not yield energy

8. Oxygenase Activity of Rubisco
The reactive nucleophile in the Rubisco reaction is the electron-rich enediol form of ribulose 1,5-bisphosphate
The active site meant for CO2 also accommodates O2
Mg++ also stabilizes the hydroperoxy anion that forms by electron transfer from the enediol to oxygen

9. FIGURE 20-20 Oxygenase activity of rubisco
FIGURE Oxygenase activity of rubisco. Rubisco can incorporate O2 rather than CO2 into ribulose 1,5-bisphosphate. The unstable intermediate thus formed splits into 2-phosphoglycolate (recycled as described in Figure 20-21) and 3-phosphoglycerate, which can reenter the Calvin cycle. 9

10. Salvage of 2-Phosphoglycerate
Complex ATP-consuming process for the recovery of C2 fragments from the photorespiration
Requires oxidation of glycolate with molecular oxygen in peroxisomes, and formation of H2O2
Involves a loss of a carbon as CO2 by mitochondrial decarboxylation of glycine

11. Glycolate pathway
FIGURE Glycolate pathway. This pathway, which salvages 2-phosphoglycolate (shaded pink) by its conversion to serine and eventually 3-phosphoglycerate, involves three cellular compartments. Glycolate formed by dephosphorylation of 2-phosphoglycolate in chloroplasts is oxidized to glyoxylate in peroxisomes and then transaminated to glycine. In mitochondria, two glycine molecules condense to form serine and the CO2 released during photorespiration (shaded green). This reaction is catalyzed by glycine decarboxylase, an enzyme present at very high levels in the mitochondria of C3 plants (see text). The serine is converted to hydroxypyruvate and then to glycerate in peroxisomes; glycerate reenters the chloroplasts to be phosphorylated, rejoining the Calvin cycle. Oxygen (shaded blue) is consumed at two steps during photorespiration. 11

12. Rubisco in C3 Plants Cannot Avoid Oxygen
Plants that assimilate dissolved CO2 in the mesophyll of the leaf into three-carbon 3-phosphoglycerate are called the C3 plants
Our atmosphere contains about 21% of oxygen and 0.038% of carbon dioxide
The dissolved concentrations in pure water are about 260 M O2 and 11 M CO2 (at the equilibrium and room temperature)
The Km of Rubisco for oxygen is about 350 M

13. Separation of CO2 capture and the Rubisco Reaction in C4 Plants
Many tropical plants avoid wasteful photorespiration by a physical separation of CO2 capture and Rubisco activity
CO2 is captured into oxaloacetate (C4) in mesophyll cells
CO2 is transported to bundle-sheath cells where Rubisco is located
The local concentration of CO2 in bundle-sheath cells is much higher than the concentration of O2

14. Carbon assimilation in C4 plants
FIGURE 20-23b Carbon assimilation in C4 plants. The C4 pathway, involving mesophyll cells and bundle-sheath cells, predominates in plants of tropical origin. (b) The C4 pathway of CO2 assimilation, which occurs through a four-carbon intermediate. 14

15. Chapter 20: Summary In this chapter, we learned that:
ATP and NADPH from light reactions are needed in order to assimilate CO2 into carbohydrates
Assimilations of three CO2 molecules via the Calvin cycle leads to the formation of one molecule of 3-phosphoglycerate
3-Phosphoglycerate is a precursor for the synthesis of larger carbohydrates such as fructose and starch
The key enzyme of the Calvin cycle, Rubisco, fixes carbon dioxide into carbohydrates
Low selectivity of Rubisco causes a wasteful incorporation of molecular oxygen in C3 plants; this is avoided in C4 plants by increasing the concentration of CO2 near Rubisco

16. Lecture Connections 18 | Amino Acid Oxidation Production of Urea
© 2009 W. H. Freeman and Company 16

17. CHAPTER 18 Amino Acid Oxidation Production of Urea
Key topics:
How proteins are digested in animals
How amino acids are degraded in animals
How urea is made in made and excreted

18. Oxidation of Amino Acids is a Significant Energy-Yielding Pathway in Carnivores
Not all organisms use amino acids as the source of energy
About 90% of energy needs of carnivores can be met by amino acids immediately after a meal
Only a small fraction of energy needs of herbivores are met by amino acids
Microorganisms scavenge amino acids from their environment for fuel

19. FIGURE 1–1c Some characteristics of living matter
FIGURE 1–1c Some characteristics of living matter. (c) Biological reproduction occurs with near-perfect fidelity. 19

20. Metabolic Circumstances of Amino Acid Oxidation
Amino acids undergo oxidative catabolism under three circumstances:
Leftover amino acids from normal protein turnover are degraded
Dietary amino acids that exceed body’s protein synthesis needs are degraded
Proteins in the body are broken down to supply amino acids for catabolism when carbohydrates are in short supply (starvation, diabetes mellitus),

21. Dietary Proteins are Enzymatically Hydrolyzed
Pepsin cuts protein into peptides in the stomach
Trypsin and chymotrypsin cut proteins and larger peptides into smaller peptides in the small intestine
Aminopeptidase and carboxypeptidases A and B degrade peptides into amino acids in the small intestine

22. 22

23. Enzymatic Degradation of Dietary Proteins

24. FIGURE 18-3 Part of the human digestive (gastrointestinal) tract
FIGURE 18-3 Part of the human digestive (gastrointestinal) tract. (a) The parietal cells and chief cells of the gastric glands secrete their products in response to the hormone gastrin. Pepsin begins the process of protein degradation in the stomach. (b) The cytoplasm of exocrine cells is completely filled with rough endoplasmic reticulum, the site of synthesis of the zymogens of many digestive enzymes. The zymogens are concentrated in membrane-enclosed transport particles called zymogen granules. When an exocrine cell is stimulated, its plasma membrane fuses with the zymogen granule membrane and zymogens are released into the lumen of the collecting duct by exocytosis. The collecting ducts ultimately lead to the pancreatic duct and thence to the small intestine. (c) Amino acids are absorbed through the epithelial cell layer (intestinal mucosa) of the villi and enter the capillaries. Recall that the products of lipid hydrolysis in the small intestine enter the lymphatic system after their absorption by the intestinal mucosa (see Figure 17-1). 24

25. Overview of Amino Acid Catabolism
FIGURE 18-1 Overview of amino acid catabolism in mammals. The amino groups and the carbon skeleton take separate but interconnected pathways 25

26. The Amino Group is Removed From All Amino Acids First
FIGURE 18-2 Amino group catabolism. (a) Overview of catabolism of amino groups (shaded) in vertebrate liver.
The Amino Group is Removed From All Amino Acids First 26

27. Fates of Nitrogen in Organisms
Plants conserve almost all the nitrogen
Many aquatic vertebrates release ammonia to their environment
Passive diffusion from epithelial cells
Active transport via gills
Many terrestrial vertebrates and sharks excrete nitrogen in the form of urea
Urea is far less toxic that ammonia
Urea has very high solubility
Some animals, such as birds and reptiles excrete nitrogen as uric acid
Uric acid is rather insoluble
Excretion as paste allows to conserve water
Humans and great apes excrete both urea (from amino acids) and uric acid (from purines)

28. Excretory Forms of Nitrogen
FIGURE 18-2b Amino group catabolism. (b) Excretory forms of nitrogen. Excess NH4+ is excreted as ammonia (microbes, bony fishes), urea (most terrestrial vertebrates), or uric acid (birds and terrestrial reptiles). Notice that the carbon atoms of urea and uric acid are highly oxidized; the organism discards carbon only after extracting most of its available energy of oxidation.
Excretory Forms of Nitrogen 28

29. Enzymatic Transamination
All aminotransferases rely on the pyridoxal phosphate cofactor
Typically, -ketoglutarate accepts amino groups
L-Glutamine acts as a temporary storage of nitrogen
L-Glutamine can donate the amino group when needed for amino acid biosynthesis

30. FIGURE 18-4 Enzyme-catalyzed transaminations
FIGURE 18-4 Enzyme-catalyzed transaminations. In many aminotransferase reactions, α-ketoglutarate is the amino group acceptor. All aminotransferases have pyridoxal phosphate (PLP) as cofactor. Although the reaction is shown here in the direction of transfer of the amino group to α-ketoglutarate, it is readily reversible 30

31. Structure of Pyridoxal Phosphate and Pyridoxamine Phosphate
Intermediate, enzyme-bound carrier of amino groups
Aldehyde form can react reversibly with amino groups
Aminated form can react reversibly with carbonyl groups

32. FIGURE 18-5a Pyridoxal phosphate, the prosthetic group of aminotransferases. (a) Pyridoxal phosphate (PLP) and its aminated form, pyridoxamine phosphate, are the tightly bound coenzymes of aminotransferases. The functional groups are shaded. 32

33. Pyridoxal Phosphate is Covalently Linked to the Enzyme In the Resting Enzyme
The linkage is made via an nucleophilic attack of the amino group an active-site lysine side chain
After dehydration, a Schiff base linkage is formed
The covalent complex is called internal aldimine because the Schiff base connects PLP to the enzyme

34. Pyridoxal phosphate is bound to the enzyme through noncovalent interactions and a Schiff-base (aldimine) linkage to a Lys residue at the active site.
FIGURE 18-5b Pyridoxal phosphate, the prosthetic group of aminotransferases. (b) Pyridoxal phosphate is bound to the enzyme through noncovalent interactions and a Schiff-base (aldimine) linkage to a Lys residue at the active site. The steps in the formation of a Schiff base from a primary amine and a carbonyl group are detailed in Figure 14-5. 34

35. PLP (red) bound to one of the two active sites of
FIGURE 18-5c Pyridoxal phosphate, the prosthetic group of aminotransferases. (c) PLP (red) bound to one of the two active sites of the dimeric enzyme aspartate aminotransferase, a typical aminotransferase
PLP (red) bound to one of the two active sites of
the dimeric enzyme aspartate aminotransferase, a typical aminotransferase 35

36. PLP (red, with yellow phosphorus) in aldimine linkage with the side chain of Lys258 (purple)
FIGURE 18-5d Pyridoxal phosphate, the prosthetic group of aminotransferases. (d) close-up view of the active site, with PLP (red, with yellow phosphorus) in aldimine linkage with the side chain of Lys258 (purple) 36

37. Chemistry of the Amino Group Removal by the Internal Aldimine
The external aldimine of PLP is a good electron sink, allowing removal of -hydrogen

38. Some amino acid transformations at the α carbon that are
facilitated by pyridoxal phosphate
MECHANISM FIGURE 18-6 (part 1) Some amino acid transformations at the α carbon that are facilitated by pyridoxal phosphate. Pyridoxal phosphate is generally bonded to the enzyme through a Schiff base, also called an internal aldimine. This activated form of PLP readily undergoes transimination to form a new Schiff base (external aldimine) with the α-amino group of the substrate amino acid (see Figure 18-5b, d). Three alternative fates for the external aldimine are shown: A transamination, B racemization, and C decarboxylation. The PLP–amino acid Schiff base is in conjugation with the pyridine ring, an electron sink that permits delocalization of an electron pair to avoid formation of an unstable carbanion on the α carbon (inset). A quinonoid intermediate is involved in all three types of reactions. The transamination route A is especially important in the pathways described in this chapter. The pathway highlighted here (shown left to right) represents only part of the overall reaction catalyzed by aminotransferases. To complete the process, a second α-keto acid replaces the one that is released, and this is converted to an amino acid in a reversal of the reaction steps (right to left). Pyridoxal phosphate is also involved in certain reactions at the β and γ carbons of some amino acids (not shown)
This activated form of PLP readily undergoes transimination to form a new Schiff base (external aldimine) with the α-amino group of the substrate amino acid (see Figure 18-5b, d). Three alternative fates for the external aldimine are shown: A transamination, B racemization, and C decarboxylation. 38

39. PLP Also Catalyzes Racemization of Amino Acids
The external aldimine of PLP is a good electron sink, allowing removal of -hydrogen

40. MECHANISM FIGURE 18-6 (part 2) Some amino acid transformations at the α carbon that are facilitated by pyridoxal phosphate. Pyridoxal phosphate is generally bonded to the enzyme through a Schiff base, also called an internal aldimine. This activated form of PLP readily undergoes transimination to form a new Schiff base (external aldimine) with the α-amino group of the substrate amino acid (see Figure 18-5b, d). Three alternative fates for the external aldimine are shown: A transamination, B racemization, and C decarboxylation. The PLP–amino acid Schiff base is in conjugation with the pyridine ring, an electron sink that permits delocalization of an electron pair to avoid formation of an unstable carbanion on the α carbon (inset). A quinonoid intermediate is involved in all three types of reactions. The transamination route A is especially important in the pathways described in this chapter. The pathway highlighted here (shown left to right) represents only part of the overall reaction catalyzed by aminotransferases. To complete the process, a second α-keto acid replaces the one that is released, and this is converted to an amino acid in a reversal of the reaction steps (right to left). Pyridoxal phosphate is also involved in certain reactions at the β and γ carbons of some amino acids (not shown) 40

41. PLP Also Catalyzes Decarboxylation of Amino Acids
The external aldimine of PLP is a good electron sink, allowing removal of -carboxylate

42. MECHANISM FIGURE 18-6 (part 3) Some amino acid transformations at the α carbon that are facilitated by pyridoxal phosphate. Pyridoxal phosphate is generally bonded to the enzyme through a Schiff base, also called an internal aldimine. This activated form of PLP readily undergoes transimination to form a new Schiff base (external aldimine) with the α-amino group of the substrate amino acid (see Figure 18-5b, d). Three alternative fates for the external aldimine are shown: A transamination, B racemization, and C decarboxylation. The PLP–amino acid Schiff base is in conjugation with the pyridine ring, an electron sink that permits delocalization of an electron pair to avoid formation of an unstable carbanion on the α carbon (inset). A quinonoid intermediate is involved in all three types of reactions. The transamination route A is especially important in the pathways described in this chapter. The pathway highlighted here (shown left to right) represents only part of the overall reaction catalyzed by aminotransferases. To complete the process, a second α-keto acid replaces the one that is released, and this is converted to an amino acid in a reversal of the reaction steps (right to left). Pyridoxal phosphate is also involved in certain reactions at the β and γ carbons of some amino acids (not shown) 42

43. Ammonia in Transported in the Bloodstream Safely as Glutamate
Un-needed glutamine is processed in intestines, kidneys and liver

44. Ammonia transport in the form of glutamine.
FIGURE 18-8 Ammonia transport in the form of glutamine. Excess ammonia in tissues is added to glutamate to form glutamine, a process catalyzed by glutamine synthetase. After transport in the bloodstream, the glutamine enters the liver and NH4+ is liberated in mitochondria by the enzyme glutaminase
Ammonia transport in the form of glutamine. 44

45. Glutamate can Donate Ammonia to Pyruvate to Make Alanine
Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy
Glycolysis yields pyruvate that muscles cannot metabolize aerobically; if not eliminated lactic acid will build up
This pyruvate can be converted to alanine for transport into liver

46. FIGURE 18-9 Glucose-alanine cycle
FIGURE 18-9 Glucose-alanine cycle. Alanine serves as a carrier of ammonia and of the carbon skeleton of pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle. 46

47. Excess Glutamate is Metabolized in the Mitochondria of Hepatocytes

48. Reactions that feed amino groups into the urea cycle
FIGURE (part 1) Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1.
Reactions that feed amino groups into the urea cycle 48

49. The Glutamate Dehydrogenase Reaction
Two-electron oxidation of glutamate followed by hydrolysis
Net process is oxidative deamination of glutamate
Occurs in mitochondrial matrix in mammals
Can use either NAD+ or NADP+ as electron acceptor

50. FIGURE 18-7 Reaction catalyzed by glutamate dehydrogenase
FIGURE 18-7 Reaction catalyzed by glutamate dehydrogenase. The glutamate dehydrogenase of mammalian liver has the unusual capacity to use either NAD+ or NADP+ as cofactor. The glutamate dehydrogenases of plants and microorganisms are generally specific for one or the other. The mammalian enzyme is allosterically regulated by GTP and ADP.
Reaction catalyzed by glutamate dehydrogenase. The glutamate dehydrogenase of mammalian liver has the unusual capacity to use either NAD+ or NADP+ as cofactor. The glutamate DHs of plants and microorganisms are generally specific for one or the other. The mammalian enzyme is allosterically regulated by GTP and ADP. 50

51. Ammonia is Re-captured via Synthesis of Carbamoyl Phosphate
This is the first nitrogen-acquiring reaction

52. Nitrogen-acquiring reactions in the synthesis of urea.
MECHANISM FIGURE 18-11a Nitrogen-acquiring reactions in the synthesis of urea. The urea nitrogens are acquired in two reactions, each requiring ATP. (a) In the reaction catalyzed by carbamoyl phosphate synthetase I, the first nitrogen enters from ammonia. The terminal phosphate groups of two molecules of ATP are used to form one molecule of carbamoyl phosphate. In other words, this reaction has two activation steps (1 and 3).
This reaction has two activation steps (1 and 3).
Nitrogen from Carbamoyl Phosphate Enters the Urea Cycle 52

53. Urea cycle and reactions that feed amino groups into the cycle
FIGURE Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1. 53

54. FIGURE (part 2) Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1. 54

55. Entry of Aspartate into the Urea Cycle
This is the second nitrogen-acquiring reaction

56. MECHANISM FIGURE 18-11b Nitrogen-acquiring reactions in the synthesis of urea. The urea nitrogens are acquired in two reactions, each requiring ATP. (b) In the reaction catalyzed by argininosuccinate synthetase, the second nitrogen enters from aspartate. Activation of the ureido oxygen of citrulline in step 1 sets up the addition of aspartate in step 2.
Nitrogen-acquiring reactions in the synthesis of urea. In the reaction catalyzed by argininosuccinate synthetase, the second nitrogen enters from aspartate. Activation of the ureido oxygen of citrulline in step 1 sets up the addition of aspartate in step 2. 56

57. Aspartate –Arginosuccinate Shunt Links Urea Cycle and Citric Acid Cycle
FIGURE Links between the urea cycle and citric acid cycle. The interconnected cycles have been called the "Krebs bicycle." The pathways linking the citric acid and urea cycles are known as the aspartate-argininosuccinate shunt; these effectively link the fates of the amino groups and the carbon skeletons of amino acids. The interconnections are even more elaborate than the arrows suggest. For example, some citric acid cycle enzymes, such as fumarase and malate dehydrogenase, have both cytosolic and mitochondrial isozymes. Fumarate produced in the cytosol—whether by the urea cycle, purine biosynthesis, or other processes—can be converted to cytosolic malate, which is used in the cytosol or transported into mitochondria (via the malateaspartate shuttle; see Figure 19-29) to enter the citric acid cycle. 57

58. Not All Amino Acids can be Synthesized in Humans
These amino acids must be obtained as dietary protein
Consumption of a variety of foods (including vegetarian only diets) well supplies all the essential amino acids

59. TABLE 18-1 Nonessential and Essential Amino Acids for Humans and the Albino Rat59

60. Fate of Individual Amino Acids
Seven to acetyl-CoA
Leu, Ile, Thr, Lys, Phe, Tyr, Trp
Six to pyruvate
Ala, Cys, Gly, Ser, Thr, Trp
Five to -ketoglutarate
Arg, Glu, Gln, His, Pro
Four to succinyl-CoA
Ile, Met, Thr, Val
Two to fumarate
Phe, Tyr
Two to oxaloacetate
Asp, Asn

61. Summary of Amino Acid Catabolism
FIGURE Summary of amino acid catabolism. Amino acids are grouped according to their major degradative end product. Some amino acids are listed more than once because different parts of their carbon skeletons are degraded to different end products. The figure shows the most important catabolic pathways in vertebrates, but there are minor variations among vertebrate species. Threonine, for instance, is degraded via at least two different pathways (see Figure 18-19, 18-27), and the importance of a given pathway can vary with the organism and its metabolic conditions. The glucogenic and ketogenic amino acids are also delineated in the figure, by color shading. 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.
Summary of Amino Acid Catabolism 61

62. Some enzyme cofactors important in one-carbon transfer reactions
FIGURE Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.
Some enzyme cofactors important in one-carbon transfer reactions

63. FIGURE (part 2) Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.

64. Conversions of one-carbon units on tetrahydrofolate
FIGURE Conversions of one-carbon units on tetrahydrofolate. The different molecular species are grouped according to oxidation state, with the most reduced at the top and most oxidized at the bottom. All species within a single shaded box are at the same oxidation state. The conversion of N5,N10-methylenetetrahydrofolate to N5-methyltetrahydrofolate is effectively irreversible. The enzymatic transfer of formyl groups, as in purine synthesis (see Figure 22-33) and in the formation of formylmethionine in bacteria (Chapter 27), generally uses N10-formyltetrahydrofolate rather than N5-formyltetrahydrofolate. The latter species is significantly more stable and therefore a weaker donor of formyl groups. N5-Formyltetrahydrofolate is a minor byproduct of the cyclohydrolase reaction, and can also form spontaneously. Conversion of N5-formyltetrahydrofolate to N5,N10-methenyltetrahydrofolate requires ATP, because of an otherwise unfavorable equilibrium. Note that N5-formiminotetrahydrofolate is derived from histidine in a pathway shown in Figure

65. Synthesis of methionine and S-adenosylmethionine in an activated-methyl cycle
FIGURE Synthesis of methionine and S-adenosylmethionine in an activated-methyl cycle. The steps are described in the text. In the methionine synthase reaction (step 4), the methyl group is transferred to cobalamin to form methylcobalamin, which in turn is the methyl donor in the formation of methionine. S-Adenosylmethionine, which has a positively charged sulfur (and is thus a sulfonium ion), is a powerful methylating agent in several biosynthetic reactions. The methyl group acceptor (step 2) is designated R.

66. Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine
FIGURE Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine. The fate of the indole group of tryptophan is shown in Figure Details of most of the reactions involving serine and glycine are shown in Figure The pathway for threonine degradation shown here accounts for only about a third of threonine catabolism (for the alternative pathway, see Figure 18-27). Several pathways for cysteine degradation lead to pyruvate. The sulfur of cysteine has several alternative fates, one of which is shown in Figure Carbon atoms here and in subsequent figures are color-coded as necessary to trace their fates.

67. FIGURE (part 1) Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine. The fate of the indole group of tryptophan is shown in Figure Details of most of the reactions involving serine and glycine are shown in Figure The pathway for threonine degradation shown here accounts for only about a third of threonine catabolism (for the alternative pathway, see Figure 18-27). Several pathways for cysteine degradation lead to pyruvate. The sulfur of cysteine has several alternative fates, one of which is shown in Figure Carbon atoms here and in subsequent figures are color-coded as necessary to trace their fates.

68. FIGURE (part 2) Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine. The fate of the indole group of tryptophan is shown in Figure Details of most of the reactions involving serine and glycine are shown in Figure The pathway for threonine degradation shown here accounts for only about a third of threonine catabolism (for the alternative pathway, see Figure 18-27). Several pathways for cysteine degradation lead to pyruvate. The sulfur of cysteine has several alternative fates, one of which is shown in Figure Carbon atoms here and in subsequent figures are color-coded as necessary to trace their fates.

69. MECHANISM FIGURE Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism. The first step in each of these reactions (not shown) involves the formation of a covalent imine linkage between enzyme-bound PLP and the substrate amino acid—serine in (a), glycine in (b) and (c). (a) A PLP-catalyzed elimination of water in the serine dehydratase reaction (step 1) begins the pathway to pyruvate. (b) In the serine hydroxymethyltransferase reaction, a PLP-stabilized carbanion (product of step 1) is a key intermediate in the reversible transfer of the methylene group (as —CH2—OH) from N5,N10-methylenetetrahydrofolate to form serine. (c) The glycine cleavage enzyme is a multienzyme complex, with components P, H, T, and L. The overall reaction, which is reversible, converts glycine to CO2 and NH4+, with the second glycine carbon taken up by tetrahydrofolate to form N5,N10-methylenetetrahydrofolate. Pyridoxal phosphate activates the α carbon of amino acids at critical stages in all these reactions, and tetrahydrofolate carries one-carbon units in two of them (see Figure 18-6, 18-17).
Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism

71. TABLE 18-2 Some Human Genetic Disorders Affecting Amino Acid Catabolism

72. FIGURE Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine. These amino acids donate some of their carbons (red) to acetyl-CoA. Tryptophan, phenylalanine, tyrosine, and isoleucine also contribute carbons (blue) to pyruvate or citric acid cycle intermediates. The phenylalanine pathway is described in more detail in Figure The fate of nitrogen atoms is not traced in this scheme; in most cases they are transferred to α-ketoglutarate to form glutamate.
Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine.

73. FIGURE (part 1) Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine. These amino acids donate some of their carbons (red) to acetyl-CoA. Tryptophan, phenylalanine, tyrosine, and isoleucine also contribute carbons (blue) to pyruvate or citric acid cycle intermediates. The phenylalanine pathway is described in more detail in Figure The fate of nitrogen atoms is not traced in this scheme; in most cases they are transferred to α-ketoglutarate to form glutamate.

74. FIGURE (part 2) Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine. These amino acids donate some of their carbons (red) to acetyl-CoA. Tryptophan, phenylalanine, tyrosine, and isoleucine also contribute carbons (blue) to pyruvate or citric acid cycle intermediates. The phenylalanine pathway is described in more detail in Figure The fate of nitrogen atoms is not traced in this scheme; in most cases they are transferred to α-ketoglutarate to form glutamate.

75. Tryptophan as precursor
FIGURE Tryptophan as precursor. The aromatic rings of tryptophan give rise to nicotinate (niacin), indoleacetate, and serotonin. Colored atoms trace the source of the ring atoms in nicotinate.
Tryptophan as precursor

76. FIGURE 18-23 Catabolic pathways for phenylalanine and tyrosine
FIGURE Catabolic pathways for phenylalanine and tyrosine. In humans these amino acids are normally converted to acetoacetyl-CoA and fumarate. Genetic defects in many of these enzymes cause inheritable human diseases (shaded yellow).
Catabolic pathways for phenylalanine and tyrosine. In humans these amino acids are normally converted to acetoacetyl-CoA and fumarate. Genetic defects in many of these enzymes cause inheritable human diseases.

77. FIGURE Role of tetrahydrobiopterin in the phenylalanine hydroxylase reaction. The H atom shaded pink is transferred directly from C-4 to C-3 in the reaction. This feature, discovered at the National Institutes of Health, is called the NIH shift.
Role of tetrahydrobiopterin in the phenylalanine hydroxylase reaction. The H atom shaded pink is transferred directly from C-4 to C-3 in the reaction. This feature, discovered at the National Institutes of Health, is called the NIH shift.

78. In PKU, phenylpyruvate accumulates in the tissues, blood, and urine
In PKU, phenylpyruvate accumulates in the tissues, blood, and urine. The urine may also contain phenylacetate and phenyllactate.
FIGURE Alternative pathways for catabolism of phenylalanine in phenylketonuria. In PKU, phenylpyruvate accumulates in the tissues, blood, and urine. The urine may also contain phenylacetate and phenyllactate.

79. Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline
FIGURE Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. These amino acids are converted to α-ketoglutarate. The numbered steps in the histidine pathway are catalyzed by 1 histidine ammonia lyase, 2 urocanate hydratase, 3 imidazolonepropionase, and 4 glutamate formimino transferase.

80. Catabolic pathways for methionine, isoleucine, threonine, and valine.
FIGURE Catabolic pathways for methionine, isoleucine, threonine, and valine. These amino acids are converted to succinyl-CoA; isoleucine also contributes two of its carbon atoms to acetyl-CoA (see Figure 18-21). The pathway of threonine degradation shown here occurs in humans; a pathway found in other organisms is shown in Figure The route from methionine to homocysteine is described in more detail in Figure 18-18; the conversion of homocysteine to α-ketobutyrate in Figure 22-14; the conversion of propionyl-CoA to succinyl-CoA in Figure

81. Catabolic pathways for the three branchedchain amino acids: valine, isoleucine, and leucine. All three pathways occur in extrahepatic tissues and share the first two enzymes, as shown here. The branched-chain α-keto acid dehydrogenase complex is analogous to the pyruvate and α-ketoglutarate dehydrogenase complexes.This enzyme is defective in people with maple syrup urine disease.
FIGURE Catabolic pathways for the three branchedchain amino acids: valine, isoleucine, and leucine. All three pathways occur in extrahepatic tissues and share the first two enzymes, as shown here. The branched-chain α-keto acid dehydrogenase complex is analogous to the pyruvate and α-ketoglutarate dehydrogenase complexes and requires the same five cofactors (some not shown here). This enzyme is defective in people with maple syrup urine disease.

82. Catabolic pathway for asparagine and aspartate
FIGURE Catabolic pathway for asparagine and aspartate. Both amino acids are converted to oxaloacetate.
Catabolic pathway for asparagine and aspartate

83. Chapter 18: Summary In this chapter, we learned that:
Amino acids from protein are an important energy source in carnivorous animals
Catabolism of amino acids involves transfer of the amino group via PLP-dependent aminotransferase to a donor such as -ketoglutarate to yield L-glutamine
L-glutamine can be used to synthesize new amino acids, or it can dispose of excess nitrogen as ammonia
In most mammals, toxic ammonia is quickly recaptured into carbamoyl phosphate and passed into the urea cycle