Protein and Amino Acid Metabolism

1
II. ????????????????
1. Disposal of Nitrogen
2. Degradation of C-skeleton
2

• ???????????? C-skeleton???????????

2. a-KG
3. Pyruvate
5. Succinyl-CoA
4. Acetyl-CoA
1. OAA
6. BCAA
3

• Glucogenic and Ketogenic amino acids

Glucogenic amino acid
Gluco-Ketogenic amino acid
Ala, Arg, Asp, Cys, Glu, Gly, His, Pro, Ser
Tyr
Met, Thr, Val
Ile, Phe, Trp
Ketcogenic amino acid
Leu, Lys
4
???????????????????
2. a-KG
1. OAA
Murray RK, et.al. p.311, 1996
5
2. ??????????????????? a-KG
Pro
Arg
dehydroproline
Orn
H2O
glutamate-g-semiald
Glu
a-KG
Forminonoglu--gt Formimino gr. to THF
His ??? 4 ???????
6
http//www.dentistry.leeds.ac.uk/biochem/MBWeb/mb2
/part1/23-aacarb.ppt
7
3. ??????????????????? Pyruvate
8
3. ??????????????????? Pyruvate
Ser
Murray RK, et.al. p.314, 1996
Gly
Murray RK, et.al. p.314, 1996
9
3. ??????????????????? Pyruvate
http//arethusa.unh.edu/bchm752/ppthtml/mar7/Mar7/
sld025.htm
10
3. ??????????????????? Pyruvate
Cystine
Murray RK, et.al. p.314, 1996
11
3. ??????????????????? Pyruvate
Cys
Murray RK, et.al. p.315, 1996
12
3. ??????????????????? Pyruvate
Threonine aldolase
http//arethusa.unh.edu/bchm752/ppthtml/mar7/Mar7/
sld025.htm
13
4. ??????????????????? Acetyl-CoA
1. Phe 2. Tyr 3. Trp ---gt---gt----gt---gta-ketoadipat
e 4. Leu (???? BCAA) 5. Lys (???????)
14
4. ??????????????????? Acetyl-CoA
Phe, Tyr
Marks DB, et.al. p.608, 1996
15
4. ??????????????????? Acetyl-CoA
Phe Hydroxylase
Marks DB, et.al. p.609, 1996
16
Hyperphenylalaninemia
17
Metabolites in PKU patients
Murray RK, et.al. p.255, 2003
18
Phenylketonuria (PKU)
O O

H3N- CH - C - N - CH - C - O-CH3
CH2
CH2
COO-
H
aspartame
Asp
Phe
19
Tyrosinemia
Tyrosinemia type I (fumarylacetoacetate
hydrolase) vomiting, diarrhea, cabbage-like
odor, photophobia, keratitis, liver kidney
failure, hepatocarcinoma----gt23/01/02 Approved
Nitisinone (Orfadin) Tyrosinemia type II eye
skin lesion, mental retardation Alkaptonuria
darkening urine, pigment deposit in connective
tissue, arthritis
20
Alkaptonuria
Chapme PC, et.al, p 272, 2005
21
5. ??????????????????? Succinyl-CoA
Met, Ile, Val
22
6. ???????????????? BCAA
Leu, Ile, Val
Marks DB, et.al. p.606, 1996
23
??????????????????????????? BCAA

• 1. Maple syrup urine disease (branched-chain
  ketonuria)
• ???? autosomal recessive disorder
• (????????????? 1 185,000 ?????????????)
• ??????????????????? maple syrup ??????????????
  ?????????????????? ?????????? ??? ????? ???????
  a-keto acid ???????????????????????????????
  ??????????
• ???????????????????????? 1 ???????????????
  ?????????????????????????? ?????????????????????
  ????????????????????????????
• ????????????????????
• ????????????????????????????????????????????????
  ?????????? ????????

a-keto acid decarboxylase complex
24
??????????????????????????? BCAA

• 2. Isovaleric acidemia
• ???? autosomal recessive disorder
• ??????? cheese ??????????????????? ???????
  acidosis ??? coma
• ???????????????????? Isovaleryl-CoA
  dehydrogenase