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氨 基 酸 代 谢. 第 七 章. Metabolism of Amino Acids. 李 志 红 医学院生物化学教研室. Topics. Nutritional Function of Protein Digestion, Absorption and Putrefaction of Proteins General Metabolism of Amino Acids Metabolism of Ammonia Metabolism of Individual Amino Acids. 第一节.

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Metabolism of Amino Acids


Topics

  • Nutritional Function of Protein

  • Digestion, Absorption and Putrefaction of Proteins

  • General Metabolism of Amino Acids

  • Metabolism of Ammonia

  • Metabolism of Individual Amino Acids


Nutritional Function of Protein


2008

  • Melamine,66%

  • 16%


2004

  • 18%12%--18%1.7%3.7%


  • Protein: the name of the protein derives from the Greek word proteios, meaning first or foremost.

  • They constitute about 50% of the cellular dry weight.

  • Function: involved in almost everything

    • Structure (collagen, elastin, keratin); Enzymes; Carriers & transport (hemoglobin); Receptors; Contraction (actin & myosin); Immune response (immunoglobulin)

    • Oxidation and supply energy


  • (nitrogen balance)

Positive: synthesis > degradation

(e.g., growth, body building)

Negative: synthesis < degradation

(e.g., starvation, trauma)

Equilibrium: synthesis = degradation

(healthy adults eating a balanced diet)


Physical requirements of proteins

  • Lowest requirement:

    30~50g/day

  • Recommend requirement:

    80g/day (65kg man)

Amino acids are not stored by the body, must be obtained from the diet, synthesized de novo.


  • (essential amino acid)

8ValIleLeuThrMetLysPheTrp

  • 12

    • Semi-essential amino acids:His,Arg

    • Required by infants and growing children


  • (nutrition value)

Beans: lysine

Grains: tryptophan


Digestion, Absorption and Putrefaction of Proteins


Dietary protein

2.1 Digestion

hydrolysis

absorb

Amino acids

Significance:

Large small Help to absorb

eliminatethe species specificity andantigenicity, avoid allergy , toxic reaction.


site:

stomach,

small intestine

    • AB

Amino acids


Aromatic amino acids

  • Initiated in stomach

  • enzymes:pepsin)

HCl

  • Stomach pH 1.5 to 2.5

  • The substrate mainly are phenylalanine,tyrosine,tryptophan

  • Products:

    polypeptides and amino acids


Protein Digestion Small Intestine

pH 7.0

    • : Arg, Lys

    • : Tyr, Trp, Phe

    • : Ala, Gly, Ser

    • AB


protease

active site

cascade reaction

Amplification effect


  • Significance

  • avoids self-digestion

  • stored and transported safely.



Protein Digestion

  • Proteins are broken down to

    • Tripeptides

    • Dipeptides

    • Free amino acids

2.2 absorption


Amino acids

carrier protein

Amino acids

Amino acids

Na+

Na+

Na+

ATP

Free Amino Acid Absorption

  • Carrier systems

    • Neutral AA

    • Basic AA

    • Acidic AA

    • Amino acids

Lumen

(small intestine)

Na+ pump

  • Entrance of some AA is via active transport

    • Requires energy

Brush broad membrance


  • -

-(-glutamyl cycle)


-

-

(Cys-Gly)

-

5-

ATP

5-

GSH

ADP+Pi

-

ATP

ADP+Pi

ATP

-

ADP+Pi



  • (putrefaction)

The products are toxic to body except few vitamin and fatty acid.



-

  • (false neurotransmitter)

(-


(ammonia)

    • pHNH3NH4+



General Metabolism of Amino Acids


  • 1%~2%

  • 70%~80%


1ATP-

  • ATP

  • (cathepsin)


2ATP-

  • ATP

  • (ubiquitin)

  • 76(8.5kD)

    • 3


  • ,3ATP

  • (proteasome)




  • 20041016


(metabolic pool)


CO2+H2O

NH3

-

+ CO2


1.

2.

3.

4.

-

(deamination)


(transamination)

Salient features?

1(transaminase)


-

-

2


GPT(ALT)

(-ketoglutarate)

Two important transaminases:

1. GPT(glutamate pyruvate transaminase)

or Alanine transaminase (ALT)


GOT(AST)

(-ketoglutarate)

2. GOT (glutamate oxaloacetate transaminase)

Or Aspartate transaminase (AST)


GOTGPT/g

GOT GPT

156 000 7 100

142 000 44 000

99 000 4 800

91 000 19 000

28 000 2 000

14 000 1 200

10 000 700

2016

GPT GOT

  • GPT

  • GOT




L-

+H2O

-H2O

NAD+

NADH+H+

NADP+ NADPH+H+

  • L-


(mostly in liver and kidney)

(Low activity in muscle)

Collection centre for amino groups


(in muscle)



NH3

Ketone bodies

oxidation

glucose

liver

urea

deamination

Amino acid


-

NH3

-

CO2 + H2O + ATP


#

#

*

*

#

#

#

*

#

CoA

CoA

#

#

#

CoA

-


Classification


  • -


  • 123456

  • 1

    2

    3CO2H2ONH3ATP


Metabolism of Ammonia


Urea

Uric acid

NH4+


  • (urea)

  • 60mol/L


AA

AA ()

AA

()

GlnE

Gln Glu +NH3

( < 60mol/L)

NH3


  • pH

PHNH4+NH3



1(muscle)

2(brain, muscle)


NH3

NH3

-

-

-


Ala-Glc

  • Ala


  • COOH

    CONH2

    CH2

    CH2

    CH2

    CH2

    CHNH2

    CHNH2

    COOH

    COOH

    (glutaminase)

    ,

    ATP

    ADP+Pi

    NH3

    +

    H2O

    (glutamic acid)


    (glutamine)

    H+

    NH4+


    +

    NH3

    + H2O

    Asparaginase

    Asparagine

    Aspartate


    (Formation of urea)

    liver

    • Urea is less toxic than ammonia.

    • The Urea Cycle occurs mainly in liver. ( ornithine cycle / Krebs cycle )

    • Most animals convert excess nitrogen to urea, prior to excreting it.

    Transportation of NH3


    :

    1932Hans Krebs Kurt Henseleit (orinithine cycle)(urea cycle)Krebs- Henseleit

    21CO211


    (urea)

    (ornithine cycle)

    (urea cycle)


    CO2 + NH3 + H2O + 2ATP

    N-Mg2+

    O

    + 2ADP + Pi

    O~PO32-

    C

    H2N

    1 NH3CO2ATP

    • (mitochondria)


    N-(AGA)

    • (carbamoyl phosphate synthetase, CPS-)

    • N-2ATP


    2

    +

    H3PO4


    NH

    2

    O

    C

    NH

    (CH

    )

    2

    3

    Mg2+

    CH

    NH

    2

    ATP

    H2O

    AMP+PPi

    COOH

    3

    • cytosol

    +


    4


    H2O

    5

    Arginase is mostly found in the liver.


    CO2 + NH3+ H2O

    2ATP

    N-

    2ADP+Pi

    Pi

    ATP

    -

    AMP + PPi

    -


    Summary of urea synthesis

    Total formula

    • One nitrogen of urea molecule comes from ammonia, another nitrogen comes from Asp.

    • HCO3- ion provides the carbon atom of urea.

    • Found primarily in liver and lesser extent in kidney

    • Synthesis of a urea will consume 3ATP (4 ~P).


    1

    2AGA CPS-

    3



    Disposal of urea

    • Urea produced in liver freely diffuses and is transported in blood to kidneys, and excreted.

    • In renal failure, the blood urea level is elevated (uremia), resulting in diffusion of more urea into intestine and its breakdown to NH3. ---hyperammonemia.

    • For these patients, oral administration of antibiotics (neomycin) to kill intestinal bacteria is advised.



    • 60mol/L

    • (hyperammonemia)

    (ammonia poisoning)


    NH3

    NH3

    -

    NADH

    ATP

    -

    TAC

    NADH


    *



    1-2

    1

    2

    3

    4


    Metabolism of Individual Amino Acids


    • Decarboxylation of amino acids

    • Metabolism of one carbon unit

    • Metabolism of sulfur-containing AAs

    • Metabolism of aromatic AAs

    • Metabolism of branched-chain AAs


    +

    CO2

    ()


    • -GABA

    • 5-5-HT


    COOH

    (CH2)2

    CHNH2

    COOH

    COOH

    (CH2)2

    CH2NH2

    L-

    CO2

    L-

    GABA

    -(-aminobutyric acid, GABA)

    • GABA

    • B6


    CH2CHCOOH

    NH2

    CO2

    CH2CH2NH2

    HN N

    HN N

    L-

    (histamine)


    CH2CHCOOH

    NH2

    HO

    HO

    CH2CHCOOH

    NH2

    CH2CH2NH2

    5-

    5-HT

    5-

    CO2

    5-5-

    (5-hydroxytryptamine, 5-HT, serotonin)

    • 5-HT


    (polyamines)


    (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

    Attention:CO2is not one carbon unit.


    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.


    • FH4

    FH4N5N10

    N5CH3FH4

    N5,N10CH2FH4

    N5,N10=CHFH4

    N10CHOFH4

    N5CH=NHFH4


    N5, N10CH2FH4

    N5, N10CH2FH4

    N5CH=NHFH4

    N10CHOFH4


    N10CHOFH4

    H+

    H2O

    NH3

    N5, N10=CHFH4

    N5CH=NHFH4

    NADPH+H+

    NADP+

    N5, N10CH2FH4

    NADH+H+

    NAD+

    N5CH3FH4

    Trap


    *

    *

    * DNA

    *


    OCU



    FH4



    1

    +

    PPi+Pi

    ATP

    S

    (S-adenosyl methionine,SAM)


    • SAM

    RH

    RCH3

    S

    SAM


    • (methionine cycle)

    ATP

    FH4

    (VitB12)

    PPi+Pi

    N5CH3FH4

    N5CH3FH4

    S-SAM

    RH

    H2O

    -CH3

    R

    S-


    RNA RNA

    DNA DNA


    (methionine cycle)

    • Met N5-CH3-FH4

    • N5-CH3-FH4B12B12FH4


    • FH4


    2

    • (creatine)(creatine phosphate)

    • SAM

    • (creatinine)


    H2O


    Metabolism of cysteine and cystine


    Formation of PAPS

    • PAPS


    CH2SH

    CH2-SO3H

    CH2-SO3H

    CHNH2

    CHNH2

    CH2NH2

    COOH

    COOH

    3[O]



    PheTyr

    PheTyr


    + H2O

    + O2

    NADP+

    NADPH+H+

    1


    • (phenyl keronuria, PKU)


    Clinic symptom


    • (melanin)

    2

    (3,4-dihydroxy-phenylalanine, DOPA)

    (Albinism)


    • (catecholamine)

    S-



    • Arvid Carlsson2000


    • (Parkinson disease)60:



    • ,

    • :


    +

    34-


    5-

    + CoA

    PP

    CoA





    -

    NH4+

    CO2

    NH3

    SO4 2-

    TCA

    NH4+

    H2O

    CO2


    • -5-

    • SAM

    • PAPS


    1

    2

    3B6?

    4?


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