Chapter 7 Amino Acid Metabolism

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Chapter 7 Amino Acid Metabolism

The biochemistry and molecular biology department
of CMU
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Section 1 Nutritional Function of Proteins

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1.1 The significance of proteins

• 1. Keep the cells and tissues growing,
  renewing and mending
• 2. Take part in some kinds of important
  physiological activities
• 3. Oxidation and supply energy

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1.2 The requirements and nutritious value of
proteins

• 1. Nitrogen balance
• Measuring the amount of intake and
  losses of total nitrogen can help us to know the
  general situation of protein metabolism.

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There are three kinds of conditions

• 1) Normal nitrogen balance
• intake N losses N
• 2) Positive nitrogen balance
• intake N gt losses N
• 3) Negative nitrogen balance
• intake N lt losses N

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2. Physical requirements of proteins

• Lowest requirement
• 3050g/day
• Recommend requirement
• 80g/day (65kg man)

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3. Nutrition value of proteins

• (1) Essential amino acids Amino acids that
  cannot be synthesized by the body and must be
  obtained from the diet.
• Eight kinds of essential AAs
• Val, Ile, Leu, Phe, Met, Trp, Thr, Lys

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• (2) Non- essential amino acids
• other 12 kinds of AAs
• (3) Semi-essential amino acids
• Tyr?Phe
• Cys?Met
• Note His and Arg are essential AAs for infants
  and children.

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(4) Complementary effect of dietary proteins

• Two or more plant proteins are consumed together
  which complement each other in essential amino
  acid content.

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Section 2 Digestion, Absorption and Putrefaction

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• 2.1 Digestion
• site stomach, small intestine
• enzymes pepsin
• Proteolytic enzymes of
  pancreatic juice

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Proteolytic enzymes of pancreatic juice
trypsin Arg, Lys (C)
chymotrypsin Tyr, Trp, Phe, Met,
Leu (C)
endopeptidases
elastase Ala, Gly, Ser (C)
carboxypeptidase
exopeptidases
aminopeptidase
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enterokinase
trypsin
trypsinogen
chymotrypsinogen
chymotrypsin
elastase
proelastase
procarboxypeptidase
carboxypeptidase
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2.2 Absorption 2.3 Putrefaction of proteins

• Concept Some undigested proteins and no absorbed
  products are anaerobic decomposed by the bacteria
  in intestine.
• The products are toxic to body except few vitamin
  and fatty acid.

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1. Production of amines
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2. Production of ammonia (NH3)

• Two sources
• (1) Metabolism on unabsorbed amino acids
• (2) Urea hydrolyzed by urease

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3. Some other toxic materials

• Tyr ? phenol
• Trp ? indole
• Cys ? hydrogen sulfide (H2S)

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Section 3 General Metabolism of Amino Acid

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3.1 The sources and fates of AAs

• Amino acid metabolic pool amino acids in
  intracellular and extracellular fluids.

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• 1. Sources of amino acids
• Dietary protein from intestine
• Breakdown of tissue protein
• Synthesis in the body

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• 2. Fates of amino acids
• Deamination
• Decarboxylation
• Synthesis of non-protein nitrogen compounds such
  as purine and pyrimidine
• Synthesis of proteins

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3.2 Degradation of protein in cells

• 1. Lysosomal pathway
• Extracellular proteins, membrane-associated
  proteins and long-lived proteins
• ATP-independent process
• Cathepsins

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• 2. Cytosol pathway
• Abnormal proteins, damaged proteins and
  short-lived proteins
• ATP and ubiquitin
• Proteasome

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3.3 The catabolism of AAs

• 1. Deamination of AAs
• Four types
• transamination
• oxidative deamination
• union deamination
• non-oxidative deamination

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(1) Transamination

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• Transamination is the process by which
  an amino group, usually from glutamate, is
  transferred to an a-keto acid, with formation of
  the corresponding amino acid plus
  a-ketoglutarate.

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• Key points
• ? reversible
• ? Lys and Pro cannot be transaminated.
• ? Aminotransferases utilize a coenzyme -
  pyridoxal phosphate - which is derived from
  vitamin B6.

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Amino acid
pyridoxal phosphate
Schiff base
pyridoxamine phosphate
a-keto acid
Isomer of Schiff base
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Two important transaminases
ALT Alanine aminotransferase (in liver)
AST Aspartate aminotransferase (in heart)
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(2) Oxidative deamination
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(3) Union deamination

• The a- amino group of most amino acids is
  transferred to a- ketoglutarate to form an a-
  keto acid and glutamate by transaminase.
  Glutamate is then oxidatively deaminated to yield
  ammonia and a- ketoglutarate by glutamate
  dehydrogenase.

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Pyruvate glutamate
Alanine a-ketoglutarate
Glutamate NAD H2O
a-ketoglutarate NADH NH4
Net Reaction Alanine NAD H2O
pyruvate NADH NH4
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(3) Purine nucleotide cycle (in muscle)

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2. Metabolism of ?-keto acid

• (1) Formation of non- essential AAs
• (2) Formation of glucose or lipids
• (3) Provide energy

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catabolites of amino acid
?-Ketoglutarate

Succinyl CoA
Intermediates of TAC
Fumarate
Oxaloacetate
PEP
Glucose
Pyruvate
Fatty acid
Acetyl CoA
Acetoacetyl CoA
Ketone bodies
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• Amino acids of converted into ketone bodies or
  fatty acids are termed ketogenic amino acids.
• Amino acids of converted into glucose are termed
  glucogenic amino acids.
• Amino acids of converted into both glucose and
  ketone bodies are termed glucogenic and ketogenic
  amino acids.

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Classification
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Section 4 Metabolism of Ammonia

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4.1 Source and outlet of ammonia (NH3)

• 1. Sources
• ? Endogenous sources
• ? Deamination of AAs--main source
• ? Catabolism of other nitrogen containing
  compounds
• ? Kidney secretion (Gln)

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? Exogenous sources

• ? Putrefaction in the intestine.
• ? Degradation of urea in the intestine

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2. Outlets

• (1) Formation of urea
• (2) Formation of Gln
• (3) Excrete in urine
• (4) Synthesis of AA

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4. 2 Transportation of NH3

• 1. Alanine-glucose cycle
• 2. Transportation of ammonia by Gln

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1. Alanine-glucose cycle

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2. Transportation of ammonia by Gln
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4. 3 Formation of urea

• 1. Site liver (mitochondria and cytosol)
• 2. Process --------- ornithine cycle

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• ? Formation of carbamoyl phosphate
• (in mitochondria)
• Carbamoyl phosphate synthetase ? (CPS?) is
  an allosteric enzyme and is absolutely dependent
  up on N-acetylglutamic acid (AGA) for its
  activity.

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• ? Formation of citrulline
• (in mitochondria)
• OCT ornithine carbamoyl transferase

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• ? Formation of arginine (in cytosol)
• two sub-steps

ASS argininosuccinate synthetase
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ASL argininosuccinate lyase
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• ? Formation of urea (in cytosol)

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• Total formula

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3. Summary of urea synthesis

• One nitrogen of urea molecule comes from
  ammonia, another nitrogen comes from Asp.
• Synthesis of a urea will consume 4 P.
• Rate limiting enzyme ASS

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Section 5 Metabolism of Specific Amino Acid

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• Decarboxylation of amino acids
• Metabolism of one carbon unit
• Metabolism of sulfur-containing AAs
• Metabolism of aromatic AAs
• Metabolism of branched-chain AAs

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5.1 Decarboxylation of amino acids
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1. Glu??-aminobutyric acid
(GABA)
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2. Cys?taurine

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3. His?histamine

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• 4. Trp?5-hydroxytryptamine (5-HT)
• (serotonin)

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• 5. Polyamines

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5.2 Metabolism of one carbon unit

• 1. One carbon unit
• One carbon units (or groups) are one
  carbon-containing groups produced in catabolism
  of some amino acids. They are

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2. Tetrahydrofolic acid (FH4)

• One carbon units are carried by FH4. The N5 and
  N10 of FH4 participate in the transfer of one
  carbon units.

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3. Formation of one carbon unit

• (1) Ser?N5,N10-CH2-FH4

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• (2) Gly?N5,N10-CH2-FH4

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• (3) His ?N5-CHNHFH4

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• (4) Trp?N10-CHOFH4

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• 4. One carbon unit exchange

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5. Significance of one carbon unit

• Substance for synthesis of nucleic acid.
• N10-CHOFH4
• N5,N10-CH2-FH4

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5.3 Metabolism of sulfur-containing AAs

• Methionine, cysteine and cystine.
• 1. Metabolism of Met

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Transmethylation and Met cycle
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Significance

• (1) SAM is the direct donor of methyl in body.
  Methylation can synthesize many important
  materials such as choline, creatine, etc.
• (2) N5-CH3FH4 is the indirect donor of methyl in
  the body.

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• (3) The free folic acid or VitB12 decrease will
  cause the decrease of DNA, which will lead to
  anemia.

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Formation of creatine

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2. Metabolism of cysteine and cystine

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Formation of PAPS

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• PAPS is the active sulfate group for addition to
  biomolecules.

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5. 4 Metabolism of aromatic
amino acids

• Phe, Tyr, Trp
• 1. Phe

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• Phe hydroxylase ??phenyl pyruvate in the body ? ?
  phenylketonuria(PKU) ? toxicity of central
  nervous system ?developmental block of
  intelligence of children
• Treatment control the input of Phe

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• 2. Tyr
• Catecholamines Dopamine, norepinephrine,
  epinephrine
• Melanin
• Tyrosinase decrease will lead to albinism.

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• 3. Trp
• 5-HT
• One carbon unit
• Nicotinic acid
• Pyruvate and Acetoacetyl CoA

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5.5 Metabolism of branched-chain AAs

• Leu, Ile, Val
• They are all essential AAs.

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Summary of metabolism

• The sources and fates of acetyl CoA

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The sources and fates of oxaloacetic acid

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