Amino Acid Metabolism Flashcards
AAs
Essential AAs
PVT TIM HA*LL
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine
Sources of Amino Acids
Protein Degredation within the cell, Degraded by digestion, AA synthesis (from TCA, Glycolysis, other AAs)
Sources of Amino Acids: Degredation within the cell
2 pathways: lysosomal degredation, UB-Proteosome system
Lysomal Degredation: enzymes (Acid hydrolases, ATP independent)
Encapsulation into membrane vesicles, fusion with lysosomes, ATP is needed to acidify the lysosome, Proteolytic degradation at acidic pH, Non specific digestion
Ubiquitin-Proteosome: in cytosol, enzymes (UB-conjugating enzymes E1, E2, E3) short lived proteins and abnormal proteins
Ubiquitination, Poly Ub is signal for proteosome complex, the proteospme unfolds, deubiquinates and cuts the target protein into fragments- specific digestion
Sources of Amino Acids: Degraded by digestion of proteins we eat
Digestion enzyme cascade: Dietary protein is cleaved to polypeptides by pepsin, then the poly peptides are cleaved into Oligo/AA trypsin/chymotrypsin/elastase, further degredation by peptidases
Action of digestive proteases:
Endopeptidases: hydrolyze peptide bonds within chains (pepsin,trypsin, chymotrypsin, elastase)
Exopeptidases: aminopeptidases remove the amino acid at the N terminus, Carboxypeptidases remove the AA at the C terminus
Most enzymes are secreted as proenzymes
Pepsinogen-> Pepsin (in acid)
Trypsinogen-> Trypsin (enteropeptidase)
Chymotrypsinogen, proelastase, and procarboxypeptidase are all activated by trypsin
Digestion in the Stomach
Protein-> Polypeptide
Parietal cells release HCl and chief cells release pepsinogen
1. Pepsinogen is autoactivated at a low pH becomes pepsin
2.pepsin active site gets exposed
3. pepsin cleaves proteins at the peptide bond N sid of aromatic AAs (Phe, Trp, Tyr, and Leu)
4. Large polypeptides result
Digestion in the intestine
Polypeptides-> peptides
Pancreatic ductal epithelial cells secrete bicarbonate, pancreatic acinar cells secrete trypsinogen, chymotrypsinogen, proelastase all as inactive zymogens, and carboxypeptidasews
Activated enzymes cleave at the C terminus
Trypsin: basic AAs
Chymotrypsin: cleaves hydrophobic/aromatic AAs
Elastase: cleaves small amino acids
Intestinal epithelial cells secrete aminopeptidases
Absorption by intestinal Epithelial Cells
Free AAs are taken up by sodium co transporters on intestinal epithelial cells
AA transporters: on all cells within the body, responsible for uptake of AA from blood and reuptake of AA in renal tubules, they are specific for classes of AA if deficient, can lead to disease
Cystinuria (COLA cystine, ornithine, lysine, Arginine)- urine issues
Hartnup disease: neutral Amino acid transporter deficiency (niacin defucuency, dermatitis, mental retardation)
Distribution of Dietary AA
Intestine–> liver via portal vein. Following a meal, insulin stimulates AA uptake from the blood by the cells throughout the body
In the liver: protein synthesis, in the body can also be used for energy
fate of free AAs
400 mg are synthesized into new proteins
100 mg are for energy production via AA Catabolism in two units (all cells have a store of AAs and if not used for proteins are used for energy(10% in fed, 33% in fasting):
Removal of the Ammonia (involves transamination, oxidative deamination, and excretion of urea)
Breakdown of Carbon skeloton (degredation of AAs form intermediates that enter gluconeogenisis and TCA)
Removal of the nitrogen from AAs
AAs for energy metabolism must be deaminated to yield the C skeleton. Transamination can be done in 3 ways: direct transamination, oxidative deamination, non oxidative deamination. The two major ones are direct transamination and oxidati
Transamination
Amino group from one AA to another, so it DOES NOT release free ammonia (rather its transferred)
The enzymes that catalyze the reactions are known as transaminases or amino transferases
ALT: transfers the ammonia from alanine to alpha-KG to yield glutamate and pyruvate
AST: transfers the ammonia from aspartate to alpha-KG to yield glutamate and oxaloacetate
ALT is in high conc. in liver, AST is in all tissues (when tissue is damaged enzymes go into the blood)
Transamination is common but not the rule (lysine, threonine, proline, and hydroxyproline do not get transaminated)
Pyridoxal phosphate (PLP) is the co-factor for ALT and AST (derived from B6)
Oxidative deamination
glutamate dehydrogenase plays an important role in nitrogen metabolism
converts glutamate into Free ammonia and alpha-KG with the production of NADPH (from the COFACTOR OF NAD)
(reaction is direction is dependent on the concentration of the substrates and the products)
Non-oxidative Deamination
Uses serine or threonine dehydratase, desulfhydrases, lyases (all use water and PLP as cofactors)
theres an unstable intermediate, and makes an alpha keto acid and free ammonia
The free ammonia goes to the blood
Transport of ammonia to the liver
Ammonia is toxic and so it gets transported to the liver in the AA form and then can be converted to urea
2 ways of transport of ammonia:
Most cells use Glutathione synthetase/ Glutaminase system (used by most cells other than muscles). Combines ammonia to glutamate to form glutamine
The glutamine is trasported to the liver by the blood, once in liver, glutaminase is converted back to glutamate and free ammonia to go into the urea cycle
Glucose/alanine cycle:
used by muscle, transamination of pyruvate from glycolysis to form alanine, alanine goes to liver, once in the liver another transaminatio of alanine to pyrvate to go to gluconeogenesis. The process also generates glutamate from alpha KG
Urea cycle
Glutamine (from tissues), Alanine (from muscle) transports ammonia to the liver.
Aspartate also feeds ammonia to the urea cycle
The toxic ammonia is converted to the urea cycle (non toxic
Fate of AAs: Carbon skeleton goes to energy production and nitrogen is used for urea synthesis
One nitrogen of urea comes from NH4 the other comes from aspartate
