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136 Cards in this Set
- Front
- Back
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Primary synthesis and catabolism site for amino acids is....
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Liver
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List the two pathways that can synthesize glutamate?
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(1) Reductive amination (from alpha-ketogluterate using GDH).
(2) Transfer of amino group by transaminase or amino transferase. |
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Which enzyme is used in the reducting amination of alpha-ketogluterate?
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Glutemate Dehydrogenase
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How is glutamine synthesized?
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By amination of glutamate using Gltamine synthetase (nitrogen group comes from NH4)
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How do you get glutamine from alpha-ketogluterate?
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Alpha-ketogluterate ---> glutamate (using GDH or transaminase) ---> Glutamne (using Glutamate synthetase)
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How is Aspargine synthesis similar/different to Glutamine synthesis?
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Both reactions are amination reaction.
Asparging gets its nitrogen group from Glutamine WHILE glutamine gets its nitrogen group from NH4. |
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How is Proline synthesized?
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By cyclization and reduction of glutamate.
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List the two ways to synthesize Serine.
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(1) From 3-phosphoglycerate By oxidation and transamination.
(2) From Glycine - through transfer of a hydroxymethyl group. |
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List four ways Glycine can be synthesized?
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(1) From Serine - Transfer of hydroxymethyl group
(2) Transamination of glyoxylate by glycine aminotransferase (3) Choline (4) From CO2 and NH4 - by mitochondrial glycine synthase complex. |
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Cysteine is synthesized from...
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Methionine and Serine
(Methionine ---> Homocysteine (+ Serine using Cystathionine-b synthase) ---> Cystathionine --> Cysteine and Alpha-Ketobutyrate |
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How is tyrosine synthesized?
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Tyrosine is synthesized from Phenylalanine (using Phenylalanine hydroxylase)
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Phenylalanine hydroxylase requires...
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Tetrahydrobiopterin and O2.
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Dihydrobiopterin
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Forms tetrahydrobipterin using NADPH.
BH4 is the coenzyme used in synthesis of Tyrosine. |
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List the precursors for following amino acids...
Glutamate Aspartate Asparigine Glutamine Tyrosine Cysteine Glycine Serine Proline Alanine |
Glutamate - Alpha-ketoglut
Aspartate - Oxaloacetate Asparigine - Aspartate Glutamine - Glutamate Tyrosine - Phenylalanine Cysteine - Methionine, Serine Glycine - Serine, Glyxoylate, Choline, Co2, NH4 Serine - 3phosphoglycerate, glycine Proline -Glutamate Alanine - Pyruvate |
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Melanin is synthesized from..
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Tyrosine
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List two deficiencies that can give rise to PKU.
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(1) Deficiency in Phenyalanine Hydroxylase
(2) Deficiency in BH2 reductase |
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BH4 is used to...
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(1) Convert L-phenylalanine to Tyrosine
(2) Synthesize catecholamines from Tyrosine (3) Synthesis of Serotonin from tryptophan. |
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Why does Vitamin C deficiency lead to Scurvy?
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Vitamin C --> Hydroxylysine
Hydroxylysine is present mostly in collagen. Hence, Vitamin C deficieny leads to spongy gums, loose teeth, fragile blood vessels etc..(SCURVY) |
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Which substrates are required to synthesize hydroxyproline?
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Vitamin C, Fe, O2 and Alpha-ketogluterate
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Tetrahydrofolate consists of...
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(1) Pteridine ring
(2) p-aminobenzoic acid (3) Glutamate (one or chain) |
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List two competetive inhibitors of DNA synthesis..
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(1) Sulfanilamide (inhibit synthesis of folic acid in microorganisms)
(2) Methotrexate - Comptetively inhibits dihydrofolate reductase (used to treat cancer) |
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Methotrexate
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A folic acid analogue that competitively inhibits dihydrofolate reductase.
Used to treat cancer (because it stops DNA replication) |
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Megaloblastic anemia
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Caused by diminished DNA synthesis.
Result of Folic acid deficiency. |
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Homocystinuria
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Due to the deficieny of Cystathionine Synthase.
Results in vascular diseases, death by MI, stroke or pulmonary embolus. |
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Cystathioninuria
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Due to deficiency of gama-cysathionase.
Results in high levels of cystathionine. |
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Methylated homocystein is...
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Methionine.
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List the two major pathways to remove L-Homocysteine.
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(1) L-Homocysteine to Methionine (requied TH4 and Vitamin B12)
(2) Formation of Cysteine (requires Vitamin B6) |
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L-Homocysteine synthesis
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From Methionine
Methionine (using SAM) ---> S-adenosylhomocysteine ---> L-Homocysteine |
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Vitamin B12 structure
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Cobalt COVALENTLY bound to Carbons of the Corrin ring.
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Pernicious Anemia
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Autoimmune destruction of the gastric parietal cells which are responsible for synthesis of glycoprotein called Intrinsic factor (B12 deficiency).
Treated with oral B12 (Cobalamin) |
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Describe folate trap hypothesis.
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L-Homocysteine + N5-Methly THF ---> Met + THF
B12 deficieny will stop above reaction. Hence, THF is in the N5-Methly THF form. This results in insufficient nucleotide and DNA synthesis. |
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Why should megaloblastic anemia be treated with Folic acid and Vitamin B12?
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Because these two are required for synthesis of Methionine
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Amino Acid pool
Total Protein in body.. Protein turnover |
100g
12Kg (in 70kg man) 300 to 400g/day |
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Describe Ubiquitination
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Tagging of traget protein with Ubiquitin (Carboxyl group of Glycine on Ubiquitin binding to amino group of Serine of the protein).
Three enzymes are involved E1 - Ubiquitin activating enzyme E2 - Ubiquitin Conjugating enzyme E3 - Ubiquitin Protein Ligase |
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Endogenous proteins are degraded by...
Exogenous proteins are degraded by... |
Ubiquitin-Proteasome Proteolytic pathway
Lysosomes |
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Cathespins
Types |
A group of lysosomal proteinases.
B and L - Cysteine proteases D - Aspartic acid protease (like pepsin) |
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Calpains
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Ca+2 dependent thiol proteases
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Kwashiorkor
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Protein depravation is larger than reduction in total calories.
Show signs of edema, inadequate growth, skin lesions, plump belly (due to edema) |
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Marasmus
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When calorie deprivation is greater than reduction in protein (protein can't be converted to calories appropriately)
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Gastric secretions consist of..
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Gastric acid (HCL) and Pepsin
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Gastric acid secretion is stimulated by...
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Histamine (a derivating of histadine)
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Pepsin
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Released by chief cells of intestine as Pepsinogen.
Pepsinogen is converte to Pepsin by HCL or other pepsin molecules. |
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Cleavage specificity for..
Trypsin Chymotrypsin Elastase Carboxypeptidase A Carboxypeptidase B |
Arg and Lysine
Trp, Tyr, Phe, Met and Leu Ala, Gly and Ser Ala, Ile, Leu, Val Arg, Lys |
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Two polypeptide hormones of intestine are..
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Cholecystokinin and Secretin
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Fuctions of...
Cholycystokinin Secretin |
Promotes zymogen secretion by pancreas.
Promotes pancreatic juice secretion to neutralize stomach acid. |
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Trypsin synthesis is stimulated by...
Trypsin activates.. |
Enteropepdiases (synthesized by intestinal mucosal cell).
Trypsin activates all other pancreatic zymogens. |
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Enteropeptidase
Aminopeptidase |
Cleaves zymogens to active enzymes.
Exopeptidase that cleaves at N-terminal to produce free AA and smaller peptides. |
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Amino acid uptake into intestinal epithelial cells..
Two types of transports |
Via Cotransport
SLC6A19 - Neutral Aminoacids (All but Lysine, Arg, Pro, Cys, Glu) SLC3A1/SCL7A9 - Dibasic amino acids (Lys, Arg, Cys) |
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Hartnup's disease
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Caused by defect in SLC6A9 - Neutral amino acid transported.
Tryptophan (hence Niacin) deficienly. Causes Pellagra like symptoms. |
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Example of selenoprotein...
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Glutathione peroxidase
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Gamma - Glutamyl cycle
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Tranport of amino acids into the intestinal cells.
Requires 3ATPs Primarily in renal system. Important for synthesis of Glutathione. |
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5-Oxoprolinuria
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Due to the deficiency in GSH-Synthetase. Also associated with gamma-glutamyl cycle (amino acid absorption system)
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Aminotrnasferase
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Transfer a-amino group to a-ketogluterate to form Glutamate.
Part of the AA degradation process. Aminotranferases are named after the amino group donor (ALT and AST). |
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Which coenzyme is required by all aminotransferase?
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PLP (pyridoxal phosphate - derivative of Vitamin B6)
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Pyridoxal phosphate
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Coenzyme required in aminotransferase reactions.
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Two major steps of amino acid degradation are..
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(1) Transamination (Using aminotransferases - ALT, AST) - Funnel amino groups to Glutamate.
(2) Glutamate Dehydrogenase - Amino group to Urea |
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Glutamate Dehydrogenase
Type of reaction... Occure in.. Coenzymes.. |
Oxidative deaminaion
Liver and Kidney NAD (loss of ammonia) or NADPH (gain of ammonia) |
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Normal ammonia level
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10-20ug/dL
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Ammonia is transported in the blood as..
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Glutamine (Glu + ammonia) - synthesized using glutamine synthetase.
Alanine (transamination of pyruvate to alanine - Glu + Pyruvate to give alanine) |
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Glutaminase versus Glutamate Dehydrogenase...
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Both used in liver to synthesize ammonia.
Glutaminase - Produce Ammonia that came from glutamine Glutamate dehydrogenase - Produce from glutamate (alanine that came from muscle) |
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Ureotelic
Uricotelic Ammonotelic |
Ureotelic - Excrete urea into their urine (human and land mammals)
Uricotelic - Excrete uric acid (bird) Ammonotelic - Ammonia diffuses out of the body (fish) |
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Uric Acid structure
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(1) One ammonia from circulation
(2) Carbon from CO2 (3) Second ammonia from Aspartate Meaning, both ammonia come from Glutamate (remember how Aspartate is synthesized) |
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List two pathways that can transfer Ammonia to liver..
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(1) Glutamine Synthetase and Glutaminase
(2) Glucose-Alanine cycle |
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What is the primary regulatory step for urea cycle?
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Carbamoyl Phosphate Synthetase I (step 1 of urea cycle)
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Allosteric activator of urea cycle step 1?
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N-Acetylglutamate
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How many moles of ATP are required for Carbamoyl-P synthesis?
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2 mol ATP (one of which serves as Phosphoryl donor)
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1st step of Urea cycle..
Enzyme Allosteric activator Substrates |
Enzyme- Mitochondrial Carbomoyl-P Synthetase I
Allosteric Activator - N-AcetylGlutamate Substrates - ATP, CO2 and NH4 |
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Carbamoyl Synthetase II
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Found in cytosol.
Uses Glutamine as nitrogen source. Functions in pyrimidine biosythesis. |
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Enzyme for Urea Cycle step 2
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L-Ornithine Transcarbamoylase
Transfers carbamoyl group to L-Ornithine and makes L-citrullin. |
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Enzyme for step 3 in urea cycle.
Energy expenditure... |
Argininosuccinate synthetase
Forms ArgininoSuccinate by adding Aspartate to L-Citrulline. (Links them via amino group of aspartate) One ATP converted to AMP. |
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Argininosuccinase
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Forms arginine and fumarate by cleaving Argininosuccinate.
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Liver Arginase
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Cleaves Arginine to form Urea and Ornithine. (cleavage at guanidine group of arginine)
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List two inhibitors of Arginase
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Ornithine and Lysine (compete with Arginine to bind to Arginase)
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Where does the two amino group come from for Urea cycle?
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Free NH3 (Glutamate is the precursor - oxidative decarboxylation)
Aspartate (Glutamate is precursor - Transamination of Asp by AST) |
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Cause of hyperammonemia type I
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Deficiency in Carbamoyl-P Synthetase I.
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Defect in Ornithine transporter results in...
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HHH
Hyperammonemia, Hyperornithinemia Homocitrullinuria (because carbamoyl-P carbamoylates Lysine to homocitrulline.) |
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How and When is Homocitrullin synthesized?
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When - Ornithine is unavailable (ornithine transport defect)
How - Carbamoyl-P carbamoylates Lysine and Homocitrullin is formed. |
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Hyperammonemia Type II
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OrnithineTranscarbamoylase defect
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Which compound binds covalently to Glutamine for its removal (when urea cycle is not working)?
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Phenylacetate (and forms phenylacetylglutamine, which can be excreted in urine)
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Which AA catabolism lead to oxaloacetate?
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Aspargine (Asparginase)
Aspartate (Transamination) |
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Which AA catabolism leads to alpha-ketogluterate?
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HGAP
Histidine (coverted to glutamate by histadase) Glutamine (Glu via glutaminase) Glutamate (via GDH) Proline (oxidized to Glu) Arginine (converted to Ornithine via Arginase. Ornithine is converted to alpha-ketogluterate) |
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List the AA that form pyruvate..
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Alanine
Serine Glycine Cystine Threonine |
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Phenylalanine breakdown..
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(1) Hydrolyzed to Tyrosine
(2) Tyrosine forms fumarate and acetoacetate. Hence, they are both ketogenic and glucogenic. |
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Which AA form fumarate?
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Phenylalanine and Tyrosin
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Alkaptonuria
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Caused by defect in tyrosine metabolism.
Deficiency in homogenistic acid oxidase, resulting in accumulation of homogenistic acid. |
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Gamma-cystathionase
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Used to synthesize cysteine from cystathionine. (vitamin B6 is used as cofactor)
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cystathionase synthase
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used to synthesize cystathionine from l-homocysteine. (vitamin B6 is a cofactor)
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Intrinsic factor
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A glycoprotein produced by gastric parietal cell.
It is necessary to absorb vitamin B12. |
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N-Acetylglutamate synthetase is activated by...
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Arginine
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Which amino acid can be converted to Pyruvate and Succinyl CoA
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Threonine
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List 4 amino acids that are both ketogenic and glucogenic.
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Phenylalanine, Tyrosine (forms fumarate and acetoacetate)
Isoleucine (forms succinylCoA and acetoacetateCoA) Tryptophan (acetoacetylCoA and one-carbon to folate) |
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List two ketogenic amino acids.
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Leucine
Lysine |
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Explain serine degradation...
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Using Serine dehyrdratase, serine is transferred into Pyruvate.
Using N5-N10MehtleneTHF, serine is transferred to Gly. Gly is converted to CO2 and NH3 using Glycine Synthase Complex in liver mito. |
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Glycine Synthase Complex
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Splits Gly into CO2 and NH4 in the liver mito.
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List the enzymes involved in the catabolism of branched chain amino acids.
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(1) Branched chain a-amino acid aminotransferase
(2) Branched chain a-ketoacid dehydrogenase comples (defect in this enzyme causes maple syrup urine syndrome) (2) Oxidative dehydrogenation |
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What are the products of the three branched Amino acid catabolism?
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Isoleucine - (longest name) Acetyl CoA and Succinyl CoA
Leucine (midlength name) - Acetyl CoA Valine (shortest name) - Succinyl CoA (1-C unit) |
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Which enzyme is required to convert Histidine to Histamine
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Broad specificity L-amino acid decarboxylase
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Which amino acids form creatine?
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Glycine
Arginine Methionine |
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Which amino acid forms NO? Describe the pathway.
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Arigine --> NO + L-Citrullin
Reaction catalyzed by NO synthase. NADPH required. |
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Which amino acid gives rise to Serotonin.
(compare this with Catecholamine synthesis) |
Tryptophan.
(Try ---> 5-Hydroxy-Try --> Serotonin) E1 - Hydroxylase E2 - Decarboxylase |
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Melatonin is formed from..
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Serotonin
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Melotonin is involved in regulating
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circadian cycle.
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Dopamine is synthesized from...
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Tyrosine
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Explain Epi synthesis..
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Tyr ---> Dopa ---> Dopamine ---> NE ---> Epi
E1 - Hydroxylase (BH4->BH2) E2 - Decarboxylase(->CO2) E3 - Dopamine-B-Hydroxylase E4 - SAM |
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Precursor of malnin
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Tyrosine
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Complete albinism results from deficiency in...
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tyrosinase.
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Thryoid hormone formation
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Iodination of tyrosine forms TH.
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Glycine is used to synthesize
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creatine, heme and purines.
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Serine participates in synthesis of
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Purine
Sphingosine Pyrimidine |
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Methionine contributes to the synthesis of
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SAM
Spermine Spermidine |
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Alternative chemical names...
Adenine Guanine Hypoxanthine Xanthine |
Adenine - 6-aminopurine
Guanine - 2-amino, 6-oxypurine Hypoxanthie - 6-oxypurine Xanthine - 2,6-dioxypurine |
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Exocylic nitrogens are on which three amino acids
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Adenine, Guanine and Cytosine
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Alternate names...
Cytosine Uracil Thymine |
Cytosine - 2-oxy,4-aminopyrimidine
Uracil - 2,4-dioxypyrimidine Thymine - 2,4-dioxy, 5-methylpyrimidine |
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How does phosphates bind to ribose (what kind of bond)?
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Ester bond
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How does ribose bind to the base?
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N-Glycosidic bond
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Which base does not have a nucleoside form
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Xanthine (2,6-dioxypurine)
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How are PO4 group attachements to nucleosides different for..
Biosynthetic substrates and Degradation products |
Biosynthetic products - Have PO4 bound to 5' carbon.
Degradation products - Have PO4 bound to 2',3' or 5' carbons. |
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Which amino acids are used in the synthesis of IMP from Ribose-5P? (to what degree).
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2Gln and Asp - provide a amino group.
Gly - is entirely used. |
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In IMP synthesis, which steps have...
Amino group donor.. Carbon donor... Glycine donor... |
Amino group donor - 1 and 4 (gln) and 7 (asp)
Carbon donor - steps 3 and 9 (THF) Glycine donor (2) |
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What is the action of
PRPP Synthase (ribose phosphpate pyrophosphokinase) |
Synthesize 5-Phosporibosyl-1-Pyrophosphpate.
(ribose5P + ATP --> 5-phosphoribosyl-1pyrophostate) |
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Which amino acids provide carbons 1, 3, 7 and 9 to purines
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1 - Aspartate
3 and 9 - Glutamine 7 - Glycine |
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What is the control step in the synthesis of IMP?
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Glutamine-PRPP aminotransferase enzyme step.
PRPP --> 5-phosphoribosyl-1amine. (in this step, amino group from glutamine is transferred to the 1 carbon of PRPP. Pyrophosphate is released ,which is quickly dehydrolyzed so that this step is irreversible.) |
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List two glutamine analogous..
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DON
Azaserine |
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How does orotate receive a Ribose-P in the UMP synthesis?
OMP is decarboxylated via ____eyzyme to _____. |
Orotate --> OMP (via - Orotate Phosphoribosyl Transferase) Group from PRPP
Via Orotidylate decarboxylase to UMP. |
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Which enzyme in the pyrimidine synthesis is in the mito?
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Dihydroorotase Dehydrogenase (to go from Dihydroorotate to Orotate)
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Which step the control step in pyrimidine synthesis?
Positive and negative feedback... |
Carbamoyl-P Synthase II.
Activated by...PRPP Inhibited by....UTP |
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Function of ATC'ase.
Stimulated by...(in bacteria) Inhibited by...(in bacteria) Inhibited by...(in humans) |
Aspartate Transcarbamoylase
Transport carbamoyl group from Carbamoyl phosphate group to Aspartate and forma N-Carbamoylaspartate Stimulated by ATP Inhibited by CTP PALA - N-Phosphoacetyla L-Aspartate |
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Which step keeps the balance between pyrimidine and purine in the pyrimidine synthesis?
How? |
CTP Synthetase step (last step).
Allosterically activated by GTP and inhibited by CTP |
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Which steps in Pyrimidine synthesis require...
ATP Amino Acids |
ATP - steps 1(2), kinase step (2), CTP Synthetase step
Gln (step 1 and 7), Aspartate (step 2) |
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Orotic Aciduria
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Due to defieciency in UMP-Synthetase.
Accumulation of Orotate (orotic acid in urine). Treated by Uracil/Uridine rich diet. |
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Pyrimidine synthesis regulation...
(1) By pyrimidine levels (2) By Purine levels |
(1) 2much UTP - Inhibit CPSII
2much CTP - Inhibit cytidylate synthetase (2) 2much GTP - Activate cytidylate synthetase 2much PRPP - Activate CPSII |
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Which enzyme do these drugs work on?
PALA 5-Azaorotate 6-Azauridine |
PALA - ATCase
5-Azaorotate - Orotate Phosphoribosyl Transferase 6-Azauridine - Orotidylate Decarboxylase |
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Describe following enzymes and their specificity.
UMP Kinase, GMP Kinase, TMP Kinase, CMP Kinase Nucleoside Diphosphate Kinase Adenylate Kinase |
These kinases are to go from Monophosphate to diphosphate. (oxy or deoxy). Thymine is only in deoxy form.
To go from Diphosphtates to triphosphate (for any base). To go from AMP -> ADP -> ATP (oxy or deoxy form) |
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Which enzyme is used to synthesize dNDP from rNDP?
How is this enzyme kept in the reduced state? |
Ribonucleotide reductase.
Kept in reduced state using... Glutaredoxin/Glutathione AND Thioredoxin/FADH2 |
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Describe Ribonucleotide Reductase
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Function: rNDP -> dNDP
Structure - 2 R1 and 2 R2 sites R2 - Has ferric iron and Tyrosine radical R1 - Primary Regulation (ON-OFF) site - ON (ATP) OFF (dATP) Substrate specifity site - 1.ATP - favors (dCDP, dUDP --->dTTP) 2.dTTP - favors (dGDP --> dGTP) 3. dGTP - favors (dADP ---> dATP) 4. dATP - turns OFF |
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Which base is not found in the the Oxy form?
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Thymine
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