Catabolism of Proteins - Biochemistry - Lecture Slides, Slides of Biochemistry

Download Catabolism of Proteins - Biochemistry - Lecture Slides and more Slides Biochemistry in PDF only on Docsity! Catabolism of proteins and amino acids Body protein Protei Reutilization for d dation new protein oo synthesis Amino acids Catabolism Figure 31-1. Protein and amino acid turnover. ® Docsity.com Reactions in the attachment of ubiquitin to proteins Oo O II II 1. UB—C —0O'+E;— SH + ATP’—> AMP '+ PP; + UB—C —S—E, O Oo lI II 2; UB—C—S—E, +E, —SH —» E,— SH+ UB— C— S—E, G OH ll Es | 3. UB—C—S—E,+H,N— €— Protein —> E,—SH + UB —C —N—€— Protein ® Docsity.com Transaminase Roles Transaminases equilibrate amino groups among available a- keto acids. This permits synthesis of non-essential amino acids, using amino groups from other amino acids & carbon skeletons synthesized in a cell. Thus a balance of different amino acids is maintained, as proteins of varied amino acid contents are synthesized. Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins). Docsity.com Transaminases function in amino acid catabolism and biosynthesis Pyruvate a-Amino acid L-Alanine a-Keto acid a-Ketoglutarate a-Amino acid L-Glutamate a-Keto acid Figure 31-5. Alanine transaminase (top) and glutamate transaminase (bottom). Docsity.com Example of a Transaminase reaction:  Aspartate donates its amino group, becoming the a-keto acid oxaloacetate.  a-Ketoglutarate accepts the amino group, becoming the amino acid glutamate. aspartate a-ketoglutarate oxaloacetate glutamate Aminotransferase (Transaminase) COO  CH2 CH2 C COO  O COO  CH2 HC COO  NH3 + COO  CH2 CH2 HC COO  NH3 + COO  CH2 C COO  O + + Docsity.com The a-amino group of a substrate amino acid displaces the enzyme lysine, to form a Schiff base linkage to PLP. The (+) charged N of PLP acts as an electron sink, to facilitate catalysis. Lysine extracts H+, promoting tautomerization, followed by reprotonation & hydrolysis. N H C O P O O O O  CH3 HC   H2 N H C H + R COO  EnzLysNH2 Amino acid-PLP Shiff base (aldimine) Docsity.com What was an amino acid leaves as an a-keto acid. The amino group remains on what is now pyridoxamine phosphate (PMP). A different a-keto acid reacts with PMP and the process reverses, to complete the reaction. N H C O P O O O OH CH3 CH2 NH2 H2 R C COO  O   EnzLysNH2 Pyridoxamine phosphate (PMP) a-keto acid Docsity.com Deamination of Amino Acids Transaminases also function to funnel amino groups from excess dietary amino acids to those amino acids (e.g., glutamate) that can be deaminated. Carbon skeletons of deaminated amino acids can be catabolized for energy, or used to synthesize glucose or fatty acids for energy storage. Only a few amino acids are deaminated directly. Docsity.com Summarized above: the role of transaminases in funneling amino N to glutamate, for deamination via Glutamate Dehydrogenase, producing NH4 +. Amino acid a-ketoglutarate NADH + NH4 + a-keto acid glutamate NAD + + H2O Transaminase Glutamate Dehydrogenase Docsity.com Amino Acid Oxidase NH,* NH,* | AMINO ACID II Cc om OXIDASE Cc oO Il ll Oo O a-Amino acid Flavin Flavin-H, —a-Imino - HO, G o CATALASE wd ar ll V20, O a-Keto acid Figure 31-7. Oxidative deamination catalyzed by -- amino acid oxidase (L-o-amino acid:O2 oxidoreductase). The a-imino acid, shown in brackets, is not a stable inter- mediate. Docsity.com Glutamine Synthetase “ TON Hen cy N90" l| II oO @) L-Glutamate Mg-ATP NHZ GLUTAMINE SYNTHETASE Mg-ADP H,0 +P; + NH3 : | ANS CHa oy #0 AO 2 ll ll O O L-Glutamine Figure 31-8. The glutamine synthase reaction. The reac- tion strongly favors glutamine synthesis. Docsity.com Muscle and liver play major roles in maintaining steady-state levels of amino acids Docsity.com Glucose-Alanine Cycle LIVER BLOOD MUSCLE Glucose Glucose Glucose Urea aT Pyruvate —NH, Pyruvate -NH, Alanine Alanine Amino acids Alanine Figure 31-12. The glucose-alanine cycle. Alanine is syn- thesized in muscle by transamination of glucose-derived Docsity.com Amino acid exchange between organs Kidney Brain (i C> Ala Muscle Figure 31-13. Summary of amino acid exchange be- tween organs immediately after feeding. Docsity.com Carbamoyl Phosphate Synthase is the committed step of the Urea Cycle, and is subject to regulation. Carbamoyl Phosphate Synthase is allosterically activated by N-acetylglutamate. This derivative of glutamate is synthesized when cellular [glutamate] is high, signaling excess of free amino acids due to protein breakdown or dietary intake. H2N C OPO3 2 O HCO3  + NH3 + 2 ATP + 2 ADP + Pi Carbamoyl Phosphate Synthase carbamoyl phosphate Docsity.com Hyperammonemia Disease Hereditary deficiency of any of the Urea Cycle enzymes leads to hyperammonemia - elevated [ammonia] in blood. Total lack of any Urea Cycle enzyme is lethal. Elevated ammonia is toxic, esp. to the brain. If not treated immediately after birth, severe mental retardation results. Docsity.com Postulated mechanisms for toxicity of high [ammonia] High NH3 would drive Glutamine Synthase: glutamate + ATP + NH 3  glutamine + ADP + P i This would deplete glutamate – a neurotransmitter & precursor for synthesis of the neurotransmitter GABA. Depletion of glutamate & high ammonia level would drive Glutamate Dehydrogenase reaction to reverse: glutamate + NAD(P)+  a-ketoglutarate + NAD(P)H + NH 4 + The resulting depletion of a-ketoglutarate, an essential Krebs Cycle intermediate would impair energy metabolism in the brain. Docsity.com