BMS100_BCH1.06_W23_BMS100 amino acid metabolism student_v2 (5).pdf

Amino acids Classifications Dr. Heisel BMS100 Objective Categorize the amino acids by polarity, describe the properties of each category and any unique groups amino acid 3 letter code FYI 1 letter code glycine Gly G alanine Ala A valine Val V leucine Leu L isoleucine Ile I m...

Amino acids Classifications Dr. Heisel BMS100 Objective Categorize the amino acids by polarity, describe the properties of each category and any unique groups amino acid 3 letter code FYI 1 letter code glycine Gly G alanine Ala A valine Val V leucine Leu L isoleucine Ile I methionine Met M phenylalanine Phe F tryptophan Trp W proline Pro P serine Ser S threonine Thr T cysteine Cys C tyrosine Tyr Y asparagine Asn N glutamine Gln Q Acidic (negative charge, hydrophilic) aspartic acid Asp D glutamic acid Glu E Basic (positive charge, hydrophilic) lysine Lys K arginine Arg R histidine His H Neutral Nonpolar (hydrophobic) Neutral Polar (hydrophilic) Blue amino acids contain sulfur Red amino acids can be phosphorylated 4 Neutral Non-Polar Aromatic (benzene ring) or aliphatic (nonbenzene hydrocarbon chain) Cys = borderline wrt polarity: sometimes grouped with neutral polar aa’s Neutral Non-Polar Unique groups - Proline Preview: Cannot rotate freely around α-C, so not found in protein structures that require rotation (ex α-helix) α-C α-C R Rotation No rotation Neutral Non-Polar Unique groups – Cysteine Thiol group can form disulfide bonds Part of many important proteins and peptides: 2 H+ Keratin (hair and nails) Insulin (lowers blood sugar) Glutathione: Gly-Cys-Glu antioxidant Insulin H2O2 H2O + H2O GS-SG GSH + GSH Held together by disulfide bond until regenerated NADP+ NADPH + H+ Neutral Non-Polar Unique groups – Cysteine and Methionine Both contain a S Can help bind metals FYI for now: iron electron carrier in the ETC can be held in place by the S of cys or met Neutral Polar OH on Ser and Thr Preview: can be site of carbohydrate attachment Site for phosphorylation Review: How can changing an OH to a P change the activity of an enzyme? NH2 on Asn Preview: can be site of carbohydrate attachment Review: What type of bonding can both the hydroxy and amido groups participate in? Charged: Acidic and Basic His often picks up an H+ to become charged At pH = 7: Acidic = negatively charged Basic = positively charged Participate in what type of bonding? Amino acids Anabolism and Catabolism Dr. Heisel BMS100 Objectives: Anabolism Describe the 3 ways N can be incorporated into amino acids (2 indirect, 1 direct) List the amino acids in each anabolic family and outline their relationship to each other, including any important reactions Describe the coenzyme function of folate and the link between folate, anemia, spina bifida, cancer Define PKU and its dietary considerations Outline the roles of histamine Amino Acid Anabolism Every amino acid includes at least 1 nitrogen There are 3 ways a N can be incorporated into an amino acid Transamination (indirect) Transamidation (indirect) Direct incorporation Amino Acid Anabolism Transamination (indirect) Transamidation (indirect) Direct incorporation Amino Acid Anabolism Transamination Review: Involves transferring an amino group from an amino acid to an alpha ketoacid α ketoacid 1 + amino acid 1 (oxaloacetate) (glutamate) amino acid 2 + α ketoacid 2 (aspartate) (α ketoglutarate) Amino Acid Anabolism Amino acid and alpha ketoacid pairs to memorize are: Alanine and ? Glutamate and alpha ketoglutarate Aspartate and oxaloacetate Amino acids Alanine Aspartate Glutamate Alpha ketoacids O = O= = O Pyruvate Oxaloacetate α-Ketoglutarate Transamination Application Review: Transaminations require a ? coenzyme (PLP) The alanine and aspartate transaminations below typically happen in the liver Enzymes = ALT and AST respectively Elevated levels of these enzymes in the blood can indicate liver problems Glutamate + pyruvate Glutamate + oxaloacetate ALT AST alpha ketoglutarate + alanine alpha ketoglutarate + aspartate Amino Acid Anabolism Transamination (indirect) Transamidation (indirect) Direct incorporation Amino Acid Anabolism Transamidation is similar to transamination, except the N comes from an amido instead of an amino = O α ketoacid + amino acid amino acid (α ketoglutarate) (glutamine, amido R-group) (glutamate) + amino acid (glutamate) Amino Acid Anabolism Transamination (indirect) Transamidation (indirect) Direct incorporation Amino Acid Anabolism Addition of N directly from ammonia Can require a B3 coenzyme = O + NAD(P)H + H+ + NH4+ Alpha ketoglutarate + NAD(P)+ + H2O Glutamate Amino Acid Anabolism The 20 amino acids belong to one of 6 amino acid families that share a common precursor: Glutamate family Aspartate family Serine family Pyruvate family Aromatic family Histidine (family) In subsequent slides, * = EAA Amino Acids: Glutamate Family Common Precursor Incorporation of N via transamination or direct incorporation Glutamate Direct incorp. of N Glutamine Arginine Proline Amino Acids: Glutamate Family Enzyme for Glu to Gln = glutamine synthetase Highly concentrated in brain Neurotoxic Glu + ATP + NH4+ Glutamine synthetase ADP + Pi + Gln To liver for Ndisposal via urea cycle Amino Acids: Asparate Family Common Precursor Incorporation of N via transamination Direct incorporation of N Aspartate Methionine* Asparagine Threonine* Lysine* Pyruvate Isoleucine* Amino Acids: Pyruvate Family Pyruvate Incorporation of N via transamination Alanine Valine* Leucine* Amino Acids: Serine Family 3-phosphoglycerate Incorporation of N via transamination Serine Cysteine Picked up by coenzyme form of B9 (folate) Glycine Lost as water More on Folate: Link to Nutrition To be used as a coenzyme, folate is first converted to THF From there, various folate coenzymes are made All assist in 1-C transfers Ex: MTHF = methyl THF, transfers methyl groups Example reactions: Ser to glycine Making purines and pyrimidines In nutrition, you will learn that folate deficiency can lead to spina bifida and anemia: what is the rationale? More on Folate: Link to Nutrition Given the link between folate and cell division: Do you think supplementing with folate can help decrease the likelihood of certain cancers, or increase their likelihood? If someone has cancer already, would it be good or bad to supplement with folate? Amino Acids: Aromatic Family Phosphoenol pyruvate + Erythrose 4-phosphate Tryptophan* Plants only Tyrosine CoQ: an important electron carrier in the ETC Animals (phenylalanine hydroxylase) Phenylalanine* Aromatic Family: Application Clinical consideration: Phenylketonuria (PKU) Autosomal recessive disorder Deficiency in phenylalanine hydroxlase Build-up of Phe occurs Phe is converted to phenylketone, excreted in urine Symptoms include: Neurological problems such as progressive mental retardation and seizures Treatment Dietary: if caught early and stay on approved diet can have normal development What dietary recommendations would you make, and why? Amino Acids: Histidine Ribose-5-phosphate Histidine can be decarboxylated to histamine Decarboxylation uses same vitamin coenzyme as transamination, = ? Histamine functions include: Histidine* Histamine Antihistamines? Gastric acid production (H2) – significance? Allergic responses (H1) Wakefulness (CNS effect, H1) Objectives: Catabolism Describe the two main pathways for N to get from extra-hepatic tissues to the liver Outline the urea cycle, including: Location The creation of carbamoyl phosphate The names of the molecules involved Arginase enzyme Where the N’s for urea come from Link to CAC Amino Acids: Catabolism Not the opposite pathways to anabolism Requires deamination to produce a carbon skeleton and an ammonium ion Amino Acid Deamination Urea NH4+ Carbon Skeleton Converted to urea in liver and excreted in urine by kidneys Feeds into ketogenic (to make ketone bodies) and/or gluconeogenic (to make glucose) cycles Amino Acids: Catabolism 2 main deamination pathways: 1) General - Extrahepatic tissues to liver: Glutamine synthetase reaction Results in glutamine carrying N to the liver to make urea Review: What are the 3 general ways of N-incorporation into amino acids? Which one is done by glutamine synthetase? Review: Which part of the body has lots of glutamine synthetase, and why? 2) Specific - Muscle to liver: Glucose-alanine cycle Results in alanine carrying N to the liver to make urea Glucose-alanine α KG Glu Working muscles breakdown protein, use glucose for energy Review at home: What enzyme and what vitamin coenzyme do the transaminations? Incorporated into urea, travels to kidney, excreted in urine Why not just send pyruvate to liver for GNG? NH4+ α KG Glu C-skeleton Amino Acids: Urea cycle Urea cycle Occurs in liver Start = combination of ornithine and carbamoyl phosphate to make citrulline A series of reactions then produces: Urea Ornithine: can be used to start cycle over again Urea has 2 N’s; One from carbamoyl phosphate Where does the carbamoyl phosphate get the N? Glucose-alanine cycle or glutamine One from aspartate Amino Acids: Urea cycle Where does carbamoyl phosphate come from? C and O come from bicarbonate P comes from ATP P is lost when combined with ornithine to make citrulline N comes from ammonia Where does the ammonia come from?!? Urea Cycle Arginase: only found in liver What is the purpose of making urea, what happens to it next? Urea cycle connects to CAC via fumarate Cytosol * * Aspartate Urea Cycle and CAC Citric Acid Cycle Acetyl CoA 2 3 Oxaloacetate Citrate 4 Fumarate Urea cycle: Asp donates its N and leaves as fumarate, which can enter CAC CAC: Oxaloacetate can undergo transamination to make Asp Amino Acids: Carbon skeletons Once the amino group has been removed, the remaining C-skeletons can be classified as: Glucogenic (aka gluconeogenic) Ketogenic Glucogenic and ketogenic – can fit into both groups Ala, Cys, Gly, Ser, Thr, Trp Leu, Phe, Tyr Ketogenesis Gluconeogenesis Pyruvate Acetoacetate Acetoacyl CoA Acetyl CoA Asp Asn Oxaloacetate Fumarate Thr, Ile CAC Succinyl CoA Citrate α-ketoglutarate Asp, Phe, Tyr Propionyl CoA Ile, Met, Val Trp, Lys For any aa’s only in blue boxes, why are they not also glucogenic? After all, acetyl CoA leads to oxaloacaetate… Glu Arg, Gln, His, Pro 43