amino acid metabolism
anabolism: proteins & N-containing compounds
• amino group → urea
⠀1. Excretion by kidney (majority)
⠀2. Excretion by intestinal tract (trace)
• carbon skeleton (α-keto acid)
⠀1. Energy + CO₂
⠀2. Glucose &/or ketone bodies
⠀3. Fatty acids
overlapping amino acid specificity
• There are many ATP using amino acid transporters with overlapping amino acid specificity → amino acids may compete for absorption.
• If an individual amino acid is consumed in great excess, this may inhibit the absorption of other amino acids.
• 76% of the AA we absorb are in SMALL PEPTIDE FORM.
• 34% are absorbed as FREE AA.
what are the two types of a.a. transporter dependency?
Na dependent (upper case letter)
Na independent (lower case letter)
1. Peptides are transported into the intestinal cell along with H+.
2. The H+ are pumped back into the intestinal lumen in exchange for Na+.
3. A NaK-ATPase pumps Na+ out of the cell in exchange for K+ across the basolateral membrane.
Peptides are cleaved to individual AA.
Absorbed AA are put into the blood by facilitated diffusion & active transport.
where are most AA catabolized?
• uses carbon skeleton for ATP production
• gets approximately 50% of its energy from AA catabolism
why must the nitrogen group be removed from AA?
So AA can be used for functions other than protein or nitrogen containing compound synthesis
how is the nitrogen group removed?
by either deamination or transamination which yields the AA's carbon skeleton
• the removal of a nitrogen group. the nitrogen group IS transferred to another compound.
• alanine aminotransferase (ALT) & aspartate aminotransferase (AST), most active in the body
• aminotransferases use vitamin B6/PLP as a coenzyme
• alanine (PLP) ↔ pyruvate; α-ketoglutarate → [ALT] glutamate
• α-ketoglutarate (PLP) ↔ glumate; asparate (AST) ↔ oxaloacetate
the removal of a nitrogen group. the amino group is NOT transferred to another compound.
threonine dehydratase, loss of water
requires pyridoxal phosphate (PLP) = Vit. B6
what can the amino group be used for?
urea synthesis (urea cycle)
• in liver
• requires E from 4 ATP
• coupled w/ TCA & ETS
• tissues send nitrogen as glutamine or alanine to liver
• glucagon ↑ the mRNA for urea cycle enzymes, stimulate gluconeogenic things
urea & TCA
1. NH3 (from glu or gln) → carbamoyl-PO4; requires 2 ATP
2. Carbamoyl-PO4 → Citrulline
3. Citrulline → Arginino-succinate; requires 2 ATP & Asp
4.1 Arginino-succinate → Arg → (Arginase) Urea & Ornithine
4.2 Arginino-succinate → Fumarate (TCA) → Oxaloacetate → [transamination] Asp
serotonin → melatonin
what AAs make glutathione?
glutathione, a patent antioxidant
glutamate, glycine, cysteine
makes compounds that stimulate cells
3. nitric oxide
glutamate & proline
NO (nitric oxide)
free radical, produced by immune system.
1. smooth muscle cell relaxation (blood pressure)
2. kills bacteria/worms.
1. dopamine → norepinephrine →epinephrine
3. thyroid hormones
what must be true for an amino acid to be gluconeogenic?
the carbon skeleton must yield a TCA cycle intermediate
what are the gluconeogenic AA?
Ala, Gly, Cys
Ser, Trp, Thr, Asp, Asn, Phe, Tyr, Val, Met, Arg, His, Pro, Glu, Gln, Ile
No Leu or Lys
1. Ala removes ammonia from the muscle
2. Ala sent to the liver
3. Ala → pyruvate
4. pyruvate → glucose
5. Glucose into blood & then into muscle as G6P
Ala helps deliver amino group to liver
intestinal cell amino acid metabolism
• SI has first access to AA. Glu is an energy component for SI, leaves glucose for RB, brain, peripheral tissues, & anaerobic conditions.
• yields oxaloacetate, citrulline (for N removal), ATP, Ala
• to portal blood: Ala, Pro, citrulline
Look at p. 170
liver AA metabolism
what are some plasma proteins?
• the liver obtains hydrophilic substances
2. retinal-binding protein
3. blood clotting proteins
5. acute phase proteins
6. heat shock proteins
transports fatty acids (which are hydrophobic)
some minerals (bind to prevent free radical production caused by free divalent cations)
• specific cell receptor, so can control which tissues & amount taken
• transports vitamin A
• lipoproteins for HDL, VLDL, LDL
• for immunoglobulin synthesis
• for transferrin synthesis for iron transport (can be regulated
acute phase proteins
• regulate systemic inflammation
• C-reactive protein (CRP): inflammation marker, binds bac for immune cell target & destruction
• fibronectin: clot formation, wound healing
• metallothionin: binds minerals like Fe to decrease bacterial growth bc bac use Fe for growth
heat shock proteins
released under stress, function not clear
nitrogen containing nonproteins
derived from amino acids
5. purine/pyrimidine bases
liver aa transport
Cys, Gly, Glu
FA transport into mitochondria
a good muscle maker
Arg, Gly, Met
functions as a reducing agent in two reactions.
In both reactions for carnitine synthesis, the vitamin is needed to reduce the iron atom that has been oxidized (Fe3+) in the reaction back to its reduced (Fe2+) state
purines & pyrimidines
pyrimdine: Glu, Asp
purine: Glu, Asp, Gly
2. thyroid hormones
4. dopamine → norepinephrine → * epinephrine
* Methylation: methionine → S-adenosyl Met (SAM) → [methyltransferase] SAH
Tyr is non-essential
how are epinephrine, norepinephrine, & dopamine related?
Norepi: No CH₃
Dopamine: No OH or CH₃
serotonin → melatonin
NAD → * NAD+
* Glutamine → Glutamate
* ATP + H₂O → [NAD Synthase] AMP + PPi
NAD+ → * NADP+
* NAD Kinase & ATP → ADP
SAM → * homocysteine
* acceptor of methyl group → [methyl transferase] methylated acceptor
methylcobalamin → [methionine synthetase, CH3 transfer] cobalamin
5-methyl tetrahydrofolate (THF) → [CH3 transfer] THF
products: cystenine, taurine, glutamate
1. + glycine → [transamidinase, kidney] ⠀guanidoacetate → * creatine
⠀⠀* Met → SAM → [methyltransferase, liver] SAH
2. [H₂O → Urea / Arginase] Ornithine → glutamate
Histidine → [decarboxylase, - CO₂] histamine
branch chain amino acid metabolism
leucine → [BCAA aminotransferase (PLP)]
Glutamine (NH₃ removal) [glutamine synthetase] ↔ [glutaminase]
Alanine (NH₃ removal)
products: ammonia or ammonium, α-ketoglutarate
1. important E source for muscle
2. stimulate PRO & glycogen synthesis (muscle recovery)
BCAA = Ile, Val
what are the breakdown components of BCAA?
• α-ketoglutarate → [BCAA transaminase] glutamate → α-ketoglutarate
• α-ketoglutarate → [BCAA transaminase] glutamate → * glutamine
⠀* ATP → [glutamine synthetase] ADP + Pi
• Asp → fumarate → TCA & ETS cycle
what are areas of BCAA/AA metabolism?
Brain: Trp → serotonin, Tyr → dopamine → norepi
Muscle: BCAA (Ile & Val)
Kidney: Urea; AA catabolism puts stress on kidney; Gln & Ala excrete amino group here
ubiquitination & protein degradation
ubqituin conjugation: marks PRO for degradation w/ ubiquitin-activating enzyme & ubiquitin-ligase complex
protein degradation: tagged goes inside a PROTEASOME, peptides & AA go into general AA pool →
2. PRO synthesis
3. further metabolism (e.g. neurotransmitters)
• ketogenesis: a way to deal w/ high FA (from adipose) oxidation to meet E needs
• glycogen is depleted within 1st day
adipose also sends FA to muscle
sepsis = systemic infection
Glutamine important E source for immune cells, will stimulate their function.
burns, sepsis, surgery, trauma → stimulation of the CNS →
1. antidiuretic hormone → water retention
2. catecholamines →
⠀• (-) insulin → hyperglycemia
⠀• (+) glucagon release → hyperglycemia & proteolysis
3. adrenocorticotropin hormne (ACTH) → (+) glucocorticoid release → gluconeogenesis → hyperglycemia
pepsinogen → [HCl or pepsin] pepsin
trypsinogen → [enteropeptidase or trypsin] trypsin