Amino Acids #1

Maternal antibodies in breast milk

• 1. HCl denatures proteins for subsequent hydrolysis by proteases
• 2. Pepsin - degrades proteins into peptides

(acid-stable endopeptidase - pepsinogen) secreted as inactive zymogen from chief cells. Activated to pepsin by HCl or autocatlyitically by other (activated) pepsin molecules. 

Denatures proteins for subsequent hydrolysis by proteases and activates pepsinogen to pepsin 

• stomach (pepsin)
• pancreas (pancreatic proteases - specific for R groups)
• SI (enteropeptidase converts trypsinogen --> trypsin)

HCl, enteropeptidase, enteropetidase (via trypsin).

Pepsinogen -- HCl --> Pepsin or autocatalytically by other activated pepsin molecules.

trypsinogen-- enteropeptidase (enzyme on intestinal mucosal cells of brush border --> trypsin; autocatalytically too. 

Trypsin = common activator of all pancreatic zymogens, so ENTEROPEPTIDASE essentially unleashes cascade of proteolytic activity. 

CCK & Secretin - both peptides. 

• CCK (mucosal cells in lower duodenum/jejunum) in response to lipids/partially digested proteins -->
• causes gallbladder to release bile & decreases gastric motility

• Secretin (other intestinal cells) in response to low pH of chyme. Acts on liver/pancreas to release soln rich
• in bicarbonate to neutralize pH for optimal pancreatic enzyme activity.

CCK: made in mucosal cells of lower duodenum/jejunum; Secretin: other intestinal cells

Activated by (CCK): partially digested lipids/proteins; (secretin): low pH of chyme

CCK causes gallbladder to release bile AND decreases gastric motility. 

Seretin acts on liver and pancreas to release soln rich in bicarbonate to neutralize pH for optimal pancreatic enzyme activity.

Free AAs - Na+ linked secondary transport system

Di/tri peptides - H+-linked transport system. 

• 1. Di/tripeptides are hydrolyzed into free amino acids in the CYTOSOL
• 2. Free AAs enter portal system
• 3. Go to liver for metabolism OR general circulation (i.e. branched AAs are not metabolized by liver instead sent from liver to muscle via blood). 
• 4. ATP-driven uptake into cells via active transport (lower AAs in EC fluid vs IC cells creating gradient maintained by active transport systems driven by ATP). 

Small intestine & kidneys

• 1. Metabolism to proteins
• 2. Urea synthesis
• 3. NH3 used for synthesis of AAs, nucleotides, and biological amines or excreted in urine. 
• 4. GNG 
• 5. Ketogenesis (only lysine & leusine are solely ketogenic)
• 6. Oxidation during starvation - reduced C skeleton is oxidized to CO2 + H2O to produce ATP. 

1. Lysine & leucine

2. GNG & Ketogenic 

• Three ties try phat ice
• Threonine, tyrosine, tryptophan, phenylalanine, isoleucine.

Oxidation of reduced C skeleton into CO2 + H2O thereby producing ATP.

• 1. Transamination (transfer of NH3 from AA to glutamate) makes pyruvate ALT
• 2. Deamination (transfer of NH3 from glutamate to OAA via glutamate dehydrogenase). makes a-ketoglutarate and aspartate

• Essential: 
• 1. Arginine - insuff syn to meet growth needs, mostly used for urea synthesis
• 2. Methionine - req in large amounts to produce cysteine (if not enough cysteine in diet)
• 3. Phenylalanine - needed in large amounts to form tyrosine (if not enough tyrosine in diet). 

Tyrosine & cysteine can become essential.

PKU can be treated via diet by restricting phenylalanine. The major result of this is that tyrosine becomes essential.

Amino acids that cannot be (1) synthesized in suffient amounts or (2) at all by humans.

• Minutes to weeks
• 400 g turned over daily
• 20 g lost daily via enzyme secretion & sloughing off of gut epithelial cells.

• 1. Steady state: Rate of protein syn = rate of protein degradation
• 2. + N balance: Rate of protein syn > rate of protein degradation
• 3. - N balance: Rate of protein syn < rate of protein degradation

• + N: caused by growth, pregnancy, recovery from injury
• - N: illness, starvation,

• 1. Lysosomes (autophagy)
• 2. Ubiquitination

• 1. Induction - after external/internal stimuli (nutrient depletion, rapamycin) mTOR is inhibited.
• 2. Autophagosome formation - cytosolic proteins are sequestered by a double-membraned vesicle
• 3. Docking and fusion with lysosome
• 4. Breakdown of autophagic vesicle and release contents for reuse by cell. 

During fasting (not for healthy cells).

• 1. Lysosomes don't require ATP
• 2. Ubiquitin is programmed cell death
• 3. Lysosomes degrade EC proteins, while proteasomes degrade endogenous proteins
• 4. Lysosome's selectivity changes depending on external environment

ATP, programmed cell death, EC vs. IC, selectivity

• 1. Ubiquitin tags proteins
• 2. Proteasomes recognize ubiquitin-tagged protein
• 3. Proteasome denatures protein, deubiquitinates it, and sends to proteolytic core for processing. REQUIRES ATP
• 4. Released peptide fragments are digested into free AAs by non-specific proteasomes in the cytosol. 

Cytosol. Proteasome digesting protein step.

It is inhibited by mTOR.

mTOR is inhibited by rapamycin and fasting (lack of insulin/amino acids)

Activated by insulin & amino acids.

1. Degrades cellular proteins & organelles to recycle nutrients or break down toxic/damaged material. 

2. Ensures vital processes can continue and prevents cell from wasting nutrients/energy.

3. Cytosolic proteins containing Lys-Phe-Glu-Arg-Gln pentapeptide sequence.

• Arginine = essential amino acid needed for proper growth and development.
• It is vital for the urea cycle.
• Arginine (from a protein rich meal) activates synthesis of N-acetylglutamate which is vital/allosteric activator of carbamoyl phosphate synthetase I - regulatory enzyme for urea cycle.

It's seen in the Lys-Phe-Glu-Arg-Gln sequence (pentapeptide that is targeted by lysosomes during autophagy)

Phenylalanine is both ketogenic & glucogenic.

It's the precursor for tyrosine.

PKU, yes it's essential.

It's seen in the pentapeptide sequence that is targeted during autophagy: Lys-Phe-Glu-Arg-Gln