1. III Bioenergetics and Metabolism
13 Principle of Bioenergetics
14 Glycolysis and the Catabolism
15 The Citric Acid Cycle
16 Oxidation of Fatty Acid
17 Amino Acid Oxidation and the Production of Urea
18 Oxidative Phosphorylation and Photophosphrylation
19 Carbohydrate Biosynthesis
20 Lipid Synthesis
21 Biosynthesis of Amino Acids, Nucleotides, and
Related Molecules
22 Integration and Hormonal Regulation of Mammalian
Metabolism

2. In animals, amino acids oxidative occurs in three different metabolic circumstances.
Some of the amino acids released during protein breakdown will undergo oxidative degradation if they are not needed for new protein synthesis.
When a diet is rich in protein and amino acids are ingested in excess of the body's needs for protein synthesis, the surplus may be catabolized, since amino acids cannot be stored.
During starvation or in diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, body proteins are called upon as fuel.

3. The metabolic energy derived from amino acids varies greatly with the type of organism.
Carnivores（食肉动物）, immediately following a meal, may obtain up to 90% of their energy requirements from amino acid oxidation.
Herbivores（食草动物）may obtain only a small fraction of their energy needs from this source.
Microorganisms can scavenge amino acids from their environment if they are available.
Amino acid catabolism does occur in plants, but it is generally concerned with the production of metabolites for other biosynthetic pathways.

5. Degradative pathway of every amino acid passes through a key step in which the a-amino group is separated from the carbon skeleton and shunted into the specialized pathways for amino group metabolism.

7. Dietary Protein Is Enzymatically Degraded to Amino Acids
Stomach
Duodenum（十二指肠）
Small intestine

8. Large Proteins Must Be Sequenced in Smaller Segments

9. In Stomach;
Entry of protein into the stomach stimulates the gastric mucosa to secrete the hormone gastrin（胃泌素）.
Which in turn stimulates the secretion of hydrochloric acid by the parietal cells of the gastric glands（胃腺）and an inactive precursor (pepsinogen，胃蛋白酶原) by the chief cells.
The pepsinogen is converted into active pepsin（胃蛋白酶）in the gastric juice（胃液）.
In the stomach, pepsin hydrolyzes ingested proteins at peptide bonds on the amino-terminal side of the aromatic amino acid residues Tyr, Phe, and Trp, long polypeptide chains is thus digested into a mixture of smaller peptides.

10. In the duodenum（十二指肠）;
The entry of peptides into the upper part of the intestine (duodenum) causes releases the hormone cholecystokinin（胆囊收缩素）, which stimulates secretion of several pancreatic inactive enzymes (trypsinogen [胰蛋白酶原], chymotrypsinogen [胰凝乳蛋白酶原], and procarboxypeptidase [羧肽酶原] A and B).

11. In the small intestine;
The inactive enzymes enter the small intestine and are converted into its active forms (trypsin [胰蛋白酶], chymotrypsin [胰凝乳蛋白酶], carboxypeptidase [羧肽酶] A and B).
The protein digestion is accomplished very efficiently because pepsin, trypsin, and chymotrypsin have different amino acid specificities.
Degradation of the short peptides is now completed by other peptidases (carboxypeptidase and aminopeptidase [氨肽酶]). Thus, the ingested proteins are sequentially hydrolyzed to yield a mixture of free amino acids, which can then be transported across the epithelial cells and enter the blood capillaries in the villi（绒毛）and are transported to the liver.

14. *** Metabolic Fats of Amino Groups
*** Nitrogen Excretion and the Urea Cycle
*** Pathway of Amino Acid Degradation

15. The amino acids Glu, Gln and Ala play especially critical roles in the amino acid oxidation pathway.
Amino groups from amino acids are transferred to α-ketoglutarate in the cytosol of liver cells to form Glu.
Excess ammonia generated in most other tissues is converted to the amide nitrogen of Gln, then transported to liver mitochondria.
In muscle, excess amino groups are generally transferred to pyruvate to form Ala. Ala is another important molecule in the transport of amino groups, conveying them from muscle to the liver.
Gln and Glu is then transported into the mitochondria, and the amino group is removed to form NH4+ .

17. If not reused for synthesis of new amino acids or other nitrogenous products, the amino groups are channeled into a single excretory end product.
Many aquatic organisms simply release ammonia as NH4+ into the surrounding medium.
Most terrestrial vertebrates first convert the ammonia into urea (humans, other mammals, and adult amphibians) or uric acid (birds, reptiles).

18. 排氨的
排尿素的
排尿酸的

19. Pyridoxal Phosphate Facilitates the Transfer of α-Amino Groups to α-ketoglutarate
氨基转移酶
The removal of the α-amino groups is promoted by enzymes aminotransferases (transaminases，转氨酶). The α-amino group is transferred to the α-carbon atom of α-ketoglutarate（α-酮戊二酸）to reactant L-Glu and α-keto acid.

20. The aminotransferases differ in their specificity for the other substrate, the L-amino acid that donates the amino group, and are named for the amino group donor.
All aminotransferases share a common prosthetic group [辅基] (pyridoxal phosphate, PLP，磷酸吡哆醛), formed of pyridoxine（吡哆醇）or vitamin B6.

21. Pyridoxal Phosphate (PLP，磷酸吡哆醛)
All aminotransferases share a common prosthetic group, formed of pyridoxine or vitamin B6. Pyridoxal phosphate functions as an intermediate carrier of amino groups at the active site of arninotransferases. PLP can accept an amino group, and its aminated form, pyridoxamine phosphate, which can donate its amino group to an α-keto acid.

22. Pyridoxal phosphate, the prosthetic group of aminotransferases

23. Three amino acid transformations facilitated by pyridoxal phosphate.
Reactions begin with formation of a new Schiff base (aldimine，醛亚胺) between the a-amino group of the amino acid and PLP, which substitutes for the enzyme-PLP linkage. The amino acid then can have three alternative fates, each involving formation of a carbanion（碳负离子）: (1) transamination（转胺）, (2) racemization（外消旋）, or (3) decarboxylation（脱羧）.

25. Glutamate Releases Ammonia in the Liver
谷氨酸脱氢酶
谷氨酸
α-酮戊二酸
In the liver, Glu is transported from the cytosol to the mitochondria, where it undergoes oxidative deamination catalyzed by L-Gln dehydrogenase and requires NAD+ (or NADP+) as the acceptor of the reducing equivalents.

26. Glutamine Transports Ammonia in the Bloodstream
Ammonia is quite toxic to animal tissues. In most animals excess ammonia is converted into a nontoxic compound before export from extrahepatic tissues into the blood and thence to the liver or kidneys. Glu, is supplanted by L-glutamine for this transport function.

27. NH4 is transported by Gln in the blood from one tissue to another

28. Alanine Transports Ammonia from Muscles to the liver
Ala also plays a special role in transporting amino groups to the liver in a nontoxic form, by the glucose-Ala cycle.
A metabolic cycle in which Ala is formed peripherally e.g. in muscle, by transamination of glucose-derived pyruvate, and is transported to the liver where its carbon skeleton is reconverted to glucose.

30. *** Metabolic Fats of Amino Groups
*** Nitrogen Excretion and the Urea Cycle
*** Pathway of Amino Acid Degradation

31. Ammonotelic animals（排氨动物）; excrete amino nitrogen as ammonia (most aquatic species, such as the bony fishes).
Ureotelic animals（排尿素动物）; excrete amino nitrogen in the form of urea (most terrestrial animals).
Uricotelic animals（排尿酸动物）; excrete amino nitrogen as uric acid (birds and reptiles).
There is no general pathway for nitrogen excretion in plants.

32. Three phases of Nitrogen excretion
(in liver cells)
Glutamine and glutamate enter the mitochondrial
Formation of carbamoyl phosphate and Asp, and first step of the urea cycle in mitochondrial matrix
Other three steps of urea cycle in the cytosol

33. Gln and Glu Enter the Mitochondrial Matrix in Liver

34. Formation of Asp and Carbamoyl Phosphate
First Step of the Urea Cycle in Mitochondrial Matrix 氨 甲酰 磷酸

35. Urea Cycle (ornithine-Urea Cycle，鸟氨酸-尿素循环)
The cycle converts waste nitrogen, in the form of highly toxic ammonium from amino acid oxidation, to essentially nontoxic urea, which then be excreted.
Urea is formed by hydrolysis of arginine to ornithine（鸟氨酸）, the cycle being complete by conversion of ornithine to citrulline（瓜氨酸）by carbamoylation（氨甲酰化）with carbamoyl phosphate, reaction of the citrulline with asparate to form argininosuccinate（精氨琥珀酸）, and cleavage of this to produce fumarate（延胡索酸）and regenerate arginine.

36. Four Steps of The Urea Cycle
Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group), and the citrulline passes into the cytosol.
Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group).
Formation of arginine from argininosuccinate, this reaction releases fumarate, which enters the citric acid cycle.
Formation of urea; this reaction regenerates ornithine.

37. Other Three Steps of Urea Cycle in the Cytosol
Activation of Citrulline

38. The Production of Urea from Ammonia Involves Five Enzymatic Steps
Step 1; Carbamoyl phosphate（氨甲酰磷酸）donates its carbamoyl group to ornithine（鸟氨酸）to form citrulline（瓜氨酸）and release Pi in a reaction catalyzed by ornithine transcarbamoylase（鸟氨酸转氨甲酰酶）. The citrulline is released from the mitochondrion into the cytosol.

39. Step 2; The second amino group is introduced from aspartate and transported to the cytosol by a condensation reaction between the amino group of aspartate and the ureido [脲基] (carbonyl) group of citrulline（瓜氨酸）. This reaction catalyzed by argininosuccinate synthetase（精氨琥珀酸合成酶）of the cytosol, requires ATP and proceeds through a citrullyl-AMP intermediate.

40. Step 3; The argininosuccinate（精氨琥珀酸）is then reversibly cleaved by argininosuccinate lyase（精氨琥珀酸裂解酶）to form free arginine and fumarate（延胡索酸）, which enters the pool of citric acid cycle intermediates.

41. Ste 4; cytosolic enzyme arginase（精氨酸酶）cleaves arginine to yield urea and ornithine. Ornithine is thus regenerated and can be transported into the mitochondrion to initiate another round of the urea cycle.

42. The Urea Cycle Ammonia urea ornithine arginine citrulline
argininosuccinate
arginine
ornithine
urea
Ammonia
Fumarate

43. The Citric Acid and Urea Cycles Can Be Linked

44. The Activity of the Urea Cycle Is Regulated at Two Levels
Carbamoyl phosphate synthetase I（氨甲酰磷酸合成酶I）, is activated by N-acetylglutamate（N-乙酰谷氨酸）, which is synthesized from acetyl-CoA and glutamate.
N-acetylglutamate synthase（N-乙酰谷氨酸合成酶）is in turn activated by arginine, a urea cycle intermediate that accumulates when urea production is too slow to accommodate the ammonia produced by amino acid catabolism.

45. Synthesis of N-acetylglutamate and its activation of carbamoyl phosphate synthetase I

46. Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis
If the urea cycle is isolation, 3 ATPs is required 2NH4+ + HCO3- + 3ATP4- + H2O
urea + 2ADP3- + 4Pi2- + AMP2- + 5H+
However, the urea cycle also cause a net conversion of oxaloacetate to fumarate (via asparate), and the gerneration of oxloacetate produces NADH in the malate dehydrogenease reaction. Each NADH can generate up to 2.5 ATPs, greatly reducing the overall energetic cost of urea synthesis.

48. Genetic Defects in the Urea Cycle Can Be Life-Threatening
The treatments are used for individual with urea cycle defects by using benzoate and phenylacetate in the diet. The chemicals combine with glysine and glutamine to help remove the ammonia.
苯甲酸
苯乙酸
苯甲酰辅酶A
苯乙酰辅酶A
马尿酸
（苯甲酰甘氨酸）
苯乙酰谷氨酰胺

49. Natural Habitat Determines the Pathway for Nitrogen Excretion
Bacteria and free-living protozoa simply release ammonia to their aqueous environment, in which it is diluted and thus made harmless.
In the bony fishes NH4+ produced by transdeamination is simply released from the liver into the blood for transport to the gills and excretion.

50. Natural Habitat Determines the Pathway for Nitrogen Excretion
3. In amphibian, tadpoles, for example, are entirely aquatic and excrete amino nitrogen as ammonia through their gills. In the adult frog, amino nitrogen is excreted almost entirely as urea
4. Birds and reptiles need to conserve water. Thus, these animals convert amino nitrogen into purines, which are catabolized to uric acid, a relatively insoluble compound excreted with the feces as a semisolid mass of uric acid crystals.

51. *** Metabolic Fats of Amino Groups
*** Nitrogen Excretion and the Urea Cycle
*** Pathway of Amino Acid Degradation

52. The 20 catabolic pathways converge to form only five products, ten amino acids are converted into acetyl-CoA, five into α-ketoglutarate, four into succinyl-CoA, two into fumarate, and two into oxaloacetate, all of which enter the citric acid cycle.

54. Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism
Key point in amino acid catabolism;
transfer one-carbon groups by enzyme cofactors (Biotin, Tetrahydrofolate and S-Adenosylmethionine)

55. Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism
The most oxidized state of carbon, CO2, is transferred by biotin.
Tetrahydrofolate is generally involved in transfers of one-carbon groups in the intermediate oxidation states.
S-adenosylmethionine in transfers of methyl groups, the most reduced state of carbon.

57. Biotin
Biotin Caboxylase
Biotin Carrier Protein
Transcarboxylase

59. S-Adenosyl-methionine

60. Ten Amino Acids Are Degraded to Acetyl-CoA
The carbon skeletons of ten amino acids yield acetyl-CoA, which enters the citric acid cycle directly.
Five of the ten (Ala, Gly, Ser, Cys, Trp and some time Thr are degraded to acetyl-CoA via pyruvate.
Six of the ten (Trp, Lys, Phe, Tyr, Leu and Ile) are converted into acetyl-CoA and/or acetoacetyl-CoA, which is then cleaved to form acetyl-CoA.

61. Catabolic pathway for Ala, Gly, Ser, Cys, Trp and Thr.

62. Two metabolic fates of Gly
丝氨酸羟甲基转移酶
N5,N10-亚甲基-四氢叶酸
甘氨酸合酶
Two metabolic fates of Gly

63. Catabolic pathway for Trp, Lys, Phe, Tyr,Leu and Ile

64. Trp as precursor 烟酸
吲哚乙酸
5-羟色胺

65. Catabolic pathway for Phe and Tyr
尿黑酸1,2-
双加氧酶
四氢生
物喋呤
苯丙氨酸
羟化酶
尿黑酸尿症
马来酰乙酰乙酸异构酶
马来酰乙酰乙酸
酪氨酸氨基
转移酶
延胡索酰乙酰乙酸
延胡索酰乙酰乙酸酶
酪氨酸血症I型
羟苯丙酮酸
p-羟苯丙酮酸
双加氧酶
3-酮脂酰辅酶A
转移酶
尿黑酸

66. 苯丙氨酸羟化酶
苯丙酮酸尿症
酪氨酸氨基转移酶
酪氨酸血症II型
p-羟苯丙酮酸双加氧酶
酪氨酸血症III型
尿黑酸1,2-双加氧酶
尿黑酸尿症

68. Five Amino Acids Are Converted into α-Ketoglutarate
The carbon skeletons of five amino acids (Arg, His, Glu, Gln, and Pro) enter the citric acid cycle via α-ketoglutarate.

69. Catabolic pathway for Arg, His, Glu, Gln and Pro
脯氨酸氧化酶
精氨酸酶
鸟氨酸δ-氨基转移酶
谷氨酸γ-半醛
Δ1-吡咯啉-5-羟酸
谷氨酸半醛
脱氢酶
四氢叶酸
N5-亚胺甲
基-四氢叶酸
谷氨酰胺酶
谷氨酸脱氢酶
Catabolic pathway for Arg, His, Glu, Gln and Pro

70. Four Amino Acids Are Converted into Succinyl-CoA
The carbon skeletons of Met, Ile, Thr, and Val are degraded by pathways that yield succinyl-CoA.

71. Catabolic pathway for met, Ile, Thr and Val
胱硫醚β-合酶
高半胱氨酸
胱硫醚γ-裂解酶
苏氨酸脱水酶
α-酮酸酸脱氢酶
丙酰辅酶A
甲基丙二酸单酰辅酶A
甲基丙二酸单酰辅酶A
变位酶

72. Branched-Chain Amino Acids Are Not Degraded in the Liver
Although much of the catabolism of amino acids occurs in liver, the three amino acids with branched side chains (Leu, Ile, and Val) are oxidized as fuels primarily in muscle, adipose, kidney, and brain tissue. These extrahepatic tissues contain a single aminotransferase not present in liver that acts on all three branched-chain amino acids to produce the corresponding α-keto acids.

73. 枫尿糖症

74. Asparagine and Aspartate Are Degraded to Oxaloacetate
The carbon skeletons of Asn and Asp ultimately enter the citric acid cycle via oxaloacetate.

75. Catabolic pathway for Asn and Asp
天冬酰胺酶
天冬氨酸氨基转移酶

76. Some Amino Acids Can Be Converted to Glucose, Others to Ketone Bodies
Some carbon atoms from six of the amino acids (those that are degraded to acetoacetyl-CoA and/or acetyl-CoA: Trp, Phe, Tyr, Ile, Leu, and Lys) can yield ketone bodies in the liver, by conversion of acetoacetyl-CoA into acetone and β-hydroxybutyrate.

78. ß oxidation
ß Oxidation in mitochondrion and peroxisome/glyoxysome
Ketone bodies
The roles of Glu, Gln and Ala in the amino acid oxidation pathway
Urea cycle
Five catabolic pathways of the 20 amino acids