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