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Questions and Answers
What is the primary element involved in the chemical transformations of amino acids that sets them apart from carbohydrates or lipids?
Which percentage of liberated amino acids from protein turnover is typically reused for new protein synthesis?
What is the function of protein turnover in muscle tissue during metabolic need?
What does the term 'half-life' refer to in protein degradation?
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Which enzyme is responsible for the conversion of dihydrobiopterin (DHB) to tetrahydrobiopterin (THB)?
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What is the major consequence of fumarylacetoacetate hydrolase deficiency in Type 1 Tyrosinemia?
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Which of the following proteins is known to have a half-life exceeding 100 hours?
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Which metabolite is elevated in cases of vitamin B6 deficiency during tryptophan degradation?
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What sequence of amino acids is associated with the rapid degradation of proteins?
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Under what conditions do cells increase the rate of protein degradation?
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What is the primary function of serotonin besides being a neurotransmitter?
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Which of the following pathways is NOT associated with the metabolism of tryptophan?
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Why is the degradation of proteins considered a seemingly wasteful process?
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What is the primary role of melatonin in the human body?
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In Type II Tyrosinemia, which of the following is a major symptom?
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How does tryptophan induce sleep?
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Which enzyme is NOT involved in protein digestion within the small intestines?
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What is the primary role of the liver in amino acid metabolism?
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Which of these pathways is associated with the conversion of an amino acid into a keto acid?
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Which method is NOT one of the ways amino acids are absorbed from the intestinal lumen?
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Which of the following amino acids is classified as purely ketogenic?
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What characterizes the ATP-independent degradation of proteins?
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Which of the following enzymes is involved in the metabolic fate of phenylalanine?
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Which type of proteolytic enzyme is primarily found in the stomach?
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What is the primary enzyme deficient in isovaleric acidemia?
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Which symptom is NOT typically associated with isovaleric acidemia?
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What is one of the products of threonine degradation via the threonine aldolase pathway?
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In homocystinuria, which enzyme's deficiency contributes to the disorder?
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Cystinuria results from a defect in renal transport mechanisms for which amino acids?
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What is the main byproduct formed in the direct oxidative pathway of cysteine metabolism?
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Which of the following pathways is involved in the degradation of threonine?
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Which statement about cystine is correct in the context of cystinuria?
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What is the primary defect in cystinosis?
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Which enzyme is primarily responsible for the major route of glycine degradation?
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Which of the following components is NOT part of the glycine cleavage system?
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Glycine plays a role in the synthesis of which of the following?
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Which amino acid is synthesized from alpha-ketoglutarate and ammonia?
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The enzyme involved in the synthesis of glutamate that accepts a methylene group is known as what?
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Which reaction will NOT lead to the creation of glutamic acid?
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Which of the following amino acids is NOT classified as nutritionally nonessential?
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Study Notes
Amino Acid Metabolism
- Amino acid metabolism is distinct from the metabolism of carbohydrates and lipids due to the involvement of nitrogen.
- Excess dietary amino acids are not excreted but converted to precursors for glucose, fatty acids, and ketone bodies, serving as metabolic fuels.
Protein Turnover
- The continuous degradation and resynthesis of all cellular proteins is called protein turnover.
- Humans turn over 1-2% of their total body protein daily, primarily muscle protein.
- 75-80% of liberated amino acids are reutilized for new protein synthesis.
- The nitrogen from the remaining 20-25% forms urea.
- The carbon skeletons are degraded to amphibolic intermediates.
Intracellular Protein Degradation
- Cellular components constantly undergo turnover.
- Proteins exhibit half-lives ranging from minutes to weeks or more.
- This continuous synthesis and degradation serves three critical functions:
- Nutrient storage and mobilization during metabolic need, particularly prominent in muscle tissue.
- Removal of abnormal proteins that could harm the cell.
- Regulation of cellular metabolism by eliminating unnecessary enzymes and regulatory proteins.
- A protein's susceptibility to degradation is expressed as its half-life, defined as the time required to reduce its concentration to 50% of its initial value.
- Liver proteins have half-lives ranging from under 30 minutes to over 150 hours.
- Short-lived proteins often possess PEST sequences – regions rich in Proline (P), Glutamate (E), Serine (S), and Threonine (T), targeting them for rapid degradation.
- Proteins with half-lives exceeding 100 hours include aldolase, lactate dehydrogenase, and cytochromes.
- Rapidly degraded enzymes often occupy crucial metabolic control points, while stable enzymes exhibit nearly constant catalytic activities across physiological conditions.
- Cellular protein degradation rates are influenced by nutritional and hormonal status.
- For example, under nutritional deprivation, cells accelerate protein degradation to supply essential nutrients for critical metabolic processes.
- Two major enzyme systems are involved in protein degradation within the cell:
- ATP-dependent Ubiquitin-proteasome system in the cytosol.
- ATP-independent degradation via lysosomes, utilizing acid hydrolases.
Overall Sources & Utilization of Amino Acids
Protein Digestion
- The mouth does not contain enzymes that break down protein.
- Pepsin, an enzyme found in the stomach, initiates protein digestion.
- The small intestine utilizes pancreatic enzymes: trypsin, chymotrypsin, carboxypeptidase, and elastase, along with enzymes produced by intestinal epithelial cells: aminopeptidases and other peptidases, to complete protein digestion.
Amino Acid Absorption
- Amino acids are absorbed from the intestinal lumen through three pathways:
- Secondary active Na+-dependent transport.
- Facilitated diffusion.
- Transport linked to the gamma-glutamyl cycle.
Central Role of the Liver in Amino Acid Metabolism
- The liver plays a central role in amino acid metabolism, performing the following functions:
- Protein synthesis: Synthesizes proteins for its own use and for delivery to other organs.
- Synthesis of other nitrogen-containing compounds: Produces various nitrogen-containing compounds.
- Delivery of a balanced mixture of amino acids to other organs.
- Catabolism of both carbon chains and nitrogen of amino acids.
- Synthesis of non-essential amino acids.
Metabolic Fates of the Keto Acids
- Keto acids can be utilized in various metabolic pathways:
- Synthetic pathway: An alpha-ketoacid reacts with ammonia to form an alpha-amino acid.
- Glucogenic pathway: Keto acids can be converted to glucose.
- Ketogenic pathway: Keto acids can be converted to ketone bodies.
- Miscellaneous pathways: Keto acids can be utilized in other metabolic processes.
Metabolic Fates [cont’d…]
- Leucine is a ketogenic amino acid.
- Both glycogenic and ketogenic: tryptophan, phenylalanine, tyrosine, lysine, isoleucine.
- Glycogenic amino acids: alanine, asparagine, glutamine, methionine, serine, arginine, cysteine, glycine, threonine, valine, aspartic acid, glutamic acid, histidine, and proline.
Metabolic Pathway of Phe/Tyr
- This pathway involves two key enzymes:
- Phenylalanine monooxygenase (phenylalanine oxidase or phenylalanine hydroxylase): Converts phenylalanine to tyrosine.
- Homogentisate 1,2-dioxygenase: Involved in the degradation of tyrosine.
- Tyrosinase: An enzyme involved in the production of melanin.
Phenylketonuria (PKU)
- This genetic disorder is characterized by a deficiency in phenylalanine hydroxylase, leading to an inability to convert phenylalanine to tyrosine.
- The accumulation of phenylalanine can cause neurological damage, intellectual disability, and seizures.
Tyrosinemias
- Two main types of tyrosinemias:
- Type 1 (Hepatorenal tyrosinemia): Deficiency of fumarylacetoacetate hydrolase, leading to the accumulation of toxic metabolites.
- Type II (Oculocutaneous tyrosinemia): Deficiency of tyrosine aminotransferase, resulting in the accumulation of tyrosine and its metabolites.
Catabolic Disposition (Fates) of Carbon Chains of Amino Acids
- The carbon chains of amino acids are degraded to various metabolic intermediates.
Metabolic Pathways of Tryptophan
- Tryptophan degradation primarily occurs through the kynurenine-anthranilate pathway:
- Tryptophan is converted to N-formylkynurenine by tryptophan oxygenase (Trp pyrrolase).
- N-formylkynurenine is further metabolized to kynurenine.
- Kynurenine is then converted to various intermediates including hydroxykynurenine, anthranilate, and nicotinamide adenine dinucleotide (NAD).
Tryptophan …
- Conversion to serotonin:
- Tryptophan is hydroxylated to 5-hydroxytryptophan.
- 5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine).
- Serotonin is a neurotransmitter and vasoconstrictor, and its degradation product, 5-hydroxyindoleacetate, is elevated in carcinoid syndrome.
Tryptophan …
- Formation of melatonin:
- Serotonin is acetylated to N-acetylserotonin.
- N-acetylserotonin is methylated by S-adenosylmethionine (SAM) to melatonin.
MELATONIN
- Melatonin is a sleep-inducing molecule.
- Acetyltransferase, found in the pineal gland and retina plays a role in melatonin synthesis.
- Melatonin regulates circadian rhythm, with increased synthesis at night.
- Tryptophan consumption induces sleepiness.
- Ingestion of tryptophan-rich foods leads to sleepiness, as serotonin also has sleep-inducing properties in addition to melatonin.
Isovaleric Acidemia
- This genetic disorder results from a deficiency in isovaleryl CoA dehydrogenase.
- Patients experience a cheesy odor in their breath and body fluids due to the accumulation of isovaleric acid.
- Excessive protein intake can trigger vomiting, acidosis, and coma.
Lysine
- Lysine is an amino acid that undergoes a series of enzymatic reactions:
- Lysine is converted to saccharopine by L-amino acid oxidase.
- Saccharopine is then metabolized to L--aminoadipic acid semialdehyde.
- Further degradation leads to the production of -aminoadipic acid, -ketoadipic acid, glutaryl CoA, crotonyl CoA, and finally acetoacetyl CoA.
Pathways for Threonine Degradation
- Threonine can be degraded through three pathways:
- Conversion to -ketobutyric acid by threonine dehydratase.
- Cleavage to glycine and acetaldehyde by threonine aldolase.
- Dehydrogenation and decarboxylation to yield aminoacetone, which is further metabolized to pyruvate.
Methionine
- Inborn errors:
- Homocystinuria: Deficiency of cystathionine synthetase.
- Cystathioninuria: Deficiency of cystathionase.
2 Principal Catabolic Pathways of Cysteine
- The primary catabolic pathways for cysteine are:
- Direct oxidative pathway (cysteine sulfinate pathway): Cysteine is converted to cysteine sulfinate and then pyruvate.
- Transamination pathway (3-mercaptopyruvate pathway): Cysteine is transaminated to 3-mercaptopyruvate, which is further degraded to pyruvate.
Inborn Errors of Cys Metabolism
- Two primary inborn errors in cysteine metabolism:
- Cystinuria (Cystine-Lysinuria): A renal transport defect, resulting in increased urinary excretion of cysteine, lysine, arginine, and ornithine.
- Cystinosis (Cystine Storage Disease): A lysosomal storage disorder, causing cystine crystal deposition in various tissues.
Pathways of Degradation of Glycine
- The major degradation pathway for glycine is via glycine synthase:
- Glycine reacts with tetrahydrofolate (FH4) and NAD+ to form N5N10-methylene FH4, CO2, NH3, NADH, and H+.
- Glycine can be converted to serine by serine hydroxymethyl transferase.
- Glycine can also undergo oxidative deamination by glycine oxidase to yield glyoxylic acid.
Glycine Cleavage system or Glycine synthase
- This multienzyme complex, resembling pyruvate dehydrogenase, consists of four protein components:
- PLP-dependent glycine decarboxylase (P Protein).
- Lipoamide-containing aminomethyl transferase (H protein)
- N5,N10-methylene THF synthesizing enzyme (T protein).
- NAD+-dependent, FAD-requiring lipoamide dehydrogenase (L protein).
Metabolic Pathways for Glycine
- Glycine is a precursor for:
- Heme synthesis.
- Synthesis of purines, where it contributes to positions 4, 5, and 7 of the purine ring.
- Glutathione, a tripeptide consisting of glycine, cysteine, and glutamate.
- Glycocholic acid, formed by conjugation with cholic acid.
- Hippuric acid, formed by conjugation with benzoic acid.
- Creatine, synthesized from glycine, arginine, and methionine.
Biosynthesis of Nutritionally Nonessential Amino acids
Nutritionally Nonessential Amino Acids
- Non-essential amino acids are synthesized by the body:
- Alanine (Ala)
- Asparagine (Asn)
- Aspartic Acid (Asp)
- Cysteine (Cys)
- Glutamic Acid (Glu)
- Glutamine (Gln)
- Glycine (Gly)
- Proline (Pro)
- Serine (Ser)
- Tyrosine (Tyr)
- Hydroxyproline (OHpro)
- Hydroxylisine (OHlys)
Synthesis of Glutamate
- Glutamate can be synthesized from alpha-ketoglutarate:
- Alpha-ketoglutarate is converted to glutamate by glutamate dehydrogenase, a reaction requiring NADPH and H+ and releasing NADP+ and H2O.
- The glutamate dehydrogenase reaction can also proceed in reverse.
Synthesis of Glutamate [cont…]
- Glutamate can also be synthesized via transamination:
- Transaminases transfer an amino group from an amino acid to an alpha-keto acid.
- For example, histidine can be converted to figlu, which is then converted to glutamic acid via transamination.
- Similarly, arginine can be converted to ornithine, and proline to pyrroline-5-carboxylic acid, both of which can be converted to glutamic acid via transamination.
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Description
Explore the intricate processes of amino acid metabolism and protein turnover. This quiz focuses on how amino acids are metabolized, the importance of protein resynthesis, and the mechanisms of intracellular protein degradation. Test your knowledge on these crucial biological functions.
