- Proposed by Hans Krebs and Kurt Henseleit in 1932 - Was the first metabolic cycle to be discovered. • Before the citric acid cycle • It is linked to the citric acid cycle. - One of the N atoms comes directly from ammonium ion, the other from aspartate. - The C atom comes from HCO 3 (CO 2 ).
- Alanine -
Transcript of "Amino acids & proteins"
Mahmoud BalbaaProfessor of BiochemistryBeirut Arab UniversityMarch 2012
Dynamics of Protein And Amino Acid MetabolismDietary Proteins Digestion to Amino Acids Transport in Blood to Cells Protein Synthesis Functional Proteins Amino Acids Protein Degradation In Proteasomes Following Tagging With Ubiquitin Metabolites 2
Digestion of ProteinsStomach: Pepsinogen Pepsin (max. act. pH 2) EnteropeptidaseSmall Intestine: Trypsinogen Trypsin Trypsin cleaves: Chymotrypsinogen to chymotrypsin Proelastase to elastase Procarboxypeptidase to carboxypeptidase Aminopeptidases (from intestinal epithelia) 3
Ketogenic Amino Acids Metabolized to acetyl CoA or acetoacetyl CoA Animals cannot convert acetyl CoA or acetoacetyl CoA to pyruvate • Isoleucine • Tryptophan • Leucine * • Phenylalanine • Lysine * • Tyrosine • Threonine * Leucine and lysine are only ketogenic 9
Urea Formation Occurs primarily in liver; excreted by kidney Principal method for removing ammonia Hyperammonemia: Defects in urea cycle enzymes (CPS, OTC, etc.) Severe neurological defects in neonates Treatment: Stop protein intake Dialysis Increase ammonia excretion: Na benzoate, Na phenylbutyrate, L-arginine, L-citrulline 12
Blood Urea Nitrogen Normal range: 7-18 mg./dL Elevated in amino acid catabolism Glutamate N-acetylglutamate CPS-1 activation Elevated in renal insufficiency Decreased in hepatic failure 13
Alkaptonuria • Deficiency of homogentisate dioxygenase • Urine turns dark on standing • Oxidation of homogentisic acid • Asymptomatic in childhood • Tendency toward arthritis in adulthood 15
Serotonin• Serotonin formed in: • Brain (neurotransmitter; regulation of sleep, mood, appetite) • Platelets (platelet aggregation, vasoconstriction) • Smooth muscle (contraction) • Gastrointestinal tract (enterochromaffin cells - major storage site)• Drugs affecting serotonin actions used to treat: • Depression •Serotonin-selective reuptake inhibitors (SSRI) • Migraine • Schizophrenia • Obsessive-compulsive disorders • Chemotherapy-induced emesis• Some hallucinogens (e.g., LSD) act as serotonin agonists 16
Proteins : Classification Solubility Albumins (s. in water and salt sol.) Globulins (s. sparingly in water, s. in salt sol.) Prolamines (s. in 70-80% ethanol, Arg rich) Histones (s. in salt sol., basic) Scleroproteins (insoluble in water and salt sol., Gly, Ala, Pro rich)
Secondary structure Spatial arrangement of AA chain Most stable structure - low energy: all -NH groups bond to -CO- groups by hydrogen bonds Within a single chain: α -helix Between two chains: β-pleated sheet o parallel o antiparallel Special type: collagen helix Also maintained by hydorphobic interactions