11_amino acids interorgan exchange (m2014)

1

Structure of a generic amino acid

Advanced Nutrition & Human Metabolism, 2009

2

** hydroxyproline & hydroxylysine content are high in collagen

3

ne

CH3 1-C

metabolism

4

Synthesis of catecholamines Tryptophan giving rise to

serotonin, melatonin & niacin

**

5

Wu G. Amino Acids, 20 March 2009

*

*

*

* *

*

Is ARG essential

to humans?

6

Summary of the metabolism of amino acids in humans.

Inborn Error of

Amino Acid Metabolism

e.g. Maple syrup urine disease

Cystathioninuria

Homocystinuria

Lippincott’s Illustrated Reviews:

Biochemistry, 2011

EMBO J 16:3373-3385, 1997

*

*

Nucleic acid—> purine uric acid

7

Reaction favors formation of Pcr at rest BUT

favors the production of ATP in exercising muscle

Serum creatinine is an important biomarker of

renal health because it is a byproduct of muscle

metabolism that is excreted unchanged by the

kidneys (easily measurable).

In the kidney, creatinine is removed from the

blood primarily by glomerular filtration, but also

by proximal tubular secretion. Little or no tubular

reabsorption of creatinine occurs.

Based on serum and urine creatinine one can

estimate creatinine clearance which correlates

with glomerular filtration rate (GFR).

spontaneous

Diabetes Care 32:424-426, 2009

Implications

Any advantage to supplement T2D and elderly with sarcopenia ?

Any unwanted side effect?

8

3-methylhistidine (for estimating protein breakdown/catabolic state)

www.mettechinc.com/.../analysis_img3.jpg

** formed post-translationally

Serum creatinine range: men 60-110 umol/l

women 45-90 umol/l

1-2% of muscle creatine is converted to creatinine daily.

Higher the muscle mass, higher the urinary level. But would also increase if intake of meat

is high or use creatine as supplement.

Meat eaters > vegetarian

Since no renal reabsorption, its level in urine could be used as a reference for other

excreted parameters [e.g. correcting for incomplete sampling or different degree of

hydration use substance to creatinine ratio]

Phenylketouria

苯酮尿症

essential for feline

redox potential / anti-oxidative

9

Interorgan amino acid exchange

and

amino acid metabolism

10

Advanced Nutrition & Human Metabolism, 2009

11

VAL

ALA

GLN

GLN

ALA

Postprandial amino acid

exchange between organs

Average diet contains

20% amino acids as BCAA

INSULIN

N extraction

Oxidation

Protein synthesis

Urea

Odd & Even Chain Fatty Acids

Odd Chain Fatty Acids

Glucogenic

Ketogenic

12

Key points on amino acid metabolism

•Adults do not store extra nitrogen derived from the diet (except ?)

•When key roles are fulfilled, surplus N will be excreted

•Transamination and deamination are key reactions for eventual catabolism

•Some amino acids are both glucogenic and ketogenic:

ILE, PHE, TRP, TYR and THR

•Glutmate is a key amino acid for N metabolism because it is deaminated at

high rate by an allosteric enzyme

Glutamate Dehydrogenase (GDH)

•GDH plays a key role in traffic control of amino acid disposal and synthesis

(non-essential amino acids)

•Can essential amino acids be “synthesized” in the body?

Degradation of the branched-chain amino acids

Lippincott’s Illustrated Reviews: Biochemistry, 2011

13

PLP = pyridoxal 5’-phosphate

14

Muscle

BCAA

15

TCA for energy

low energy level

Liver (periportal hepatocytes)

Brain (neurons)

Kidney (renal tubules

GABA Glutamate

decarboxylase

16

https://www.bioscience.org/2007/v12/af/2067/fig2.jpg

Schematic representation of key

metabolic processes involved in

glutamate homeostasis related to

neurotransmitter release in a

glutamatergic synapse interacting with a

surrounding astrocyte. The vesicular pool

of Glu is highlighted by an ellipse.

Glycolysis and TCA cycle metabolism are

indicated in both cellular compartments

and in the astrocytic compartment

pyruvate carboxylation to oxaloacetate

via pyruvate carboxylase (PC) is

included. The glutamate-glutamine cycle

including the reactions catalyzed by

glutamine synthetase (GS) and phosphate

activated glutaminase are indicated in the

astrocytic and neuronal compartment,

respectively. Abbreviations: CIT, citrate;

GLN, glutamine; GLU, glutamate; GS,

glutamine synthetase; α-KG, α-

ketoglutarate; PAG, phosphate activated

glutaminase; PC, pyruvate carboxylase;

PDH, pyruvate dehydrogenase; PYR

pyruvate; TCA, tricarboxylic acid.

Diet

Proteolysis