Chapter 18 Bcm 2

Flashcard 1

Question: What are the two broad parts involved in the pathways for amino acid catabolism? Answer: The many paths for amino acid catabolism have two broad parts, one involving the amino groups and the other involving the carbon skeletons^[1].

Flashcard 2

Question: What happens to the α-amino group during amino acid catabolism? Answer: The α-amino group is separated from the carbon skeleton in a key step, always involving a pyridoxal phosphate cofactor, and shunted into the pathways of amino group metabolism^[1].

Flashcard 3

Question: What happens to the carbon skeletons during amino acid catabolism? Answer: The carbon skeletons are broken down to citric acid cycle intermediates^[1].

Flashcard 4

Question: How are metabolic pathways for amino acid catabolism structured relative to other pathways? Answer: Metabolic pathways are not distinct; the various pathways for amino acid catabolism are elaborately intertwined with other catabolic and anabolic pathways^[1][2].

Flashcard 5

Question: Why must excess amino groups be safely excreted, and what cycle serves this purpose in mammals? Answer: Free ammonia is toxic, so excess amino groups must be safely excreted; in mammals, the urea cycle serves this purpose^[1].

Flashcard 6

Question: What are the catabolic fates of amino acids and their carbon skeletons? Answer: Each amino acid has a different catabolic fate, and their varied carbon skeletons are broken down via equally varied pathways; all can be oxidized to generate ATP^[1][3].

Flashcard 7

Question: Which amino acids cannot contribute to gluconeogenesis? Answer: All amino acids except leucine and lysine can contribute to gluconeogenesis when needed^[1][3].

Flashcard 8

Question: What is the first condition under which amino acids undergo oxidative degradation? Answer: Amino acids undergo oxidative degradation when amino acids released during protein turnover are not needed for new protein synthesis^[1].

Flashcard 9

Question: What are the second and third conditions under which amino acids undergo oxidative degradation? Answer: Amino acids undergo oxidative degradation when ingested amino acids exceed the body’s needs for protein synthesis, or when cellular proteins are used as fuel because carbohydrates are unavailable or not properly utilized^[1].

Flashcard 10

Question: What happens to amino groups during catabolism unless they are reused? Answer: Unless reused, amino groups are channeled into a single excretory end product^[1].

Flashcard 11

Question: What happens to carbon, hydrogen, and oxygen during the catabolism of nitrogen-containing macromolecules? Answer: During the catabolism of nitrogen-containing macromolecules, carbon, hydrogen, and oxygen are extracted and stored in the form of carbohydrates and fats^[1].

Flashcard 12

Question: Why is excess nitrogen excreted from the body? Answer: As nitrogenous wastes tend to form toxic ammonia, which raises the pH of body fluids, excess nitrogen is excreted from the body^[1].

Flashcard 13

Question: What energy and resource requirements are associated with the formation of ammonia itself? Answer: The formation of ammonia itself requires a lot of ATP and large quantities of water to dilute it out of a cell and body^[1].

Flashcard 14

Question: What are the predominant nitrogen waste products excreted by animals? Answer: Animals excrete a variety of nitrogen waste products, but ammonia, urea, and uric acid predominate^[1].

Flashcard 15

Question: What is a major factor in determining the mode of nitrogen excretion in animals? Answer: A major factor in determining the mode of nitrogen excretion is the availability of water in the environment^[1].

Flashcard 16

Question: How do ammonotelic animals excrete amino nitrogen? Answer: Ammonotelic animals that live in aquatic environments excrete amino nitrogen as ammonia^[1].

Flashcard 17

Question: How do ureotelic terrestrial organisms detoxify amino nitrogen? Answer: Ureotelic terrestrial organisms, including mammals, detoxify amino nitrogen by converting it into a relatively nontoxic form, urea^[1].

Flashcard 18

Question: How do uricotelic animals excrete amino nitrogen? Answer: Uricotelic animals like birds, reptiles, and many terrestrial invertebrates excrete amino nitrogen as uric acid, but most N waste goes out as urea^[1].

Flashcard 19

Question: Which four amino acids play key roles in the transport and distribution of amino groups? Answer: Four amino acids—alanine, glutamate, glutamine, and aspartate—play key roles in the transport and distribution of amino groups^[1].

Flashcard 20

Question: What tissue concentration and metabolic features characterize alanine, glutamate, glutamine, and aspartate? Answer: All four are present in relatively high concentrations in many mammalian tissues and are readily converted to key citric acid cycle intermediates^[1].

Flashcard 21

Question: What specific citric acid cycle intermediates are glutamate, glutamine, alanine, and aspartate converted into? Answer: Glutamate is converted to α-ketoglutarate, glutamine to α-ketoglutarate, alanine to pyruvate, and aspartate to oxaloacetate^[1].

Flashcard 22

Question: What is the action of pepsin after protein ingestion? Answer: After ingestion of proteins, pepsin in the low pH of stomach cleaves long polypeptide chains into a mixture of smaller peptides^[1].

Flashcard 23

Question: What is secretin and where is it produced? Answer: Secretin is a peptide hormone produced by the S cells in the duodenum in response to low pH in the small intestine^[1].

Flashcard 24

Question: What are the digestive functions of secretin? Answer: Secretin stimulates the pancreas to secrete bicarbonate and water into the small intestine, neutralize gastric acid, maintain an optimal pH for digestion, and influence digestive juice secretion from stomach and liver^[1].

Flashcard 25

Question: What osmoregulatory function does secretin share? Answer: Secretin also has osmoregulatory functions similar to those of angiotensin II^[1].

Flashcard 26

Question: What triggers the secretion of cholecystokinin and what is its site of secretion? Answer: Cholecystokinin is a hormone secreted by the duodenum in response to the arrival of peptides in the duodenum^[1].

Flashcard 27

Question: What pancreatic proteases are stimulated by cholecystokinin? Answer: Cholecystokinin stimulates secretion of several pancreatic proteases: trypsinogen, chymotrypsinogen, and procarboxypeptidases A and B^[1][2].

Flashcard 28

Question: What are trypsinogen, chymotrypsinogen, and procarboxypeptidases A and B? Answer: Trypsinogen is the zymogen of trypsin, chymotrypsinogen is the zymogen of chymotrypsin, and procarboxypeptidases A and B are the zymogens of carboxypeptidases A and B^[2].

Flashcard 29

Question: What is enteropeptidase and what is its function? Answer: Enteropeptidase is a proteolytic enzyme that converts trypsinogen to trypsin^[2].

Flashcard 30

Question: What enzymes does trypsin activate once formed? Answer: Trypsin activates additional trypsinogen, chymotrypsinogen, the procarboxypeptidases, and proelastase^[2].

Flashcard 31

Question: What is the function of pancreatic trypsin inhibitor? Answer: Pancreatic trypsin inhibitor is a protein inhibitor that further protects the pancreas against self-digestion^[2].

Flashcard 32

Question: How are free amino acids absorbed in the intestinal mucosa? Answer: Free amino acids are transported into the epithelial cells lining the small intestine, enter the blood capillaries in the villi, and travel to the liver^[2].

Flashcard 33

Question: What causes acute pancreatitis? Answer: Acute pancreatitis is caused by obstruction of the pathway by which pancreatic secretions enter the intestine^[2].

Flashcard 34

Question: What are the primary and contributing causes of acute pancreatitis? Answer: Primarily caused by gallstones and heavy alcohol consumption, but medications, elevated blood triglycerides, hypercalcemia, infections, physical abdominal injury or surgery, and genetic factors also contribute^[2].

Flashcard 35

Question: What cellular event occurs inside pancreatic cells during acute pancreatitis? Answer: Zymogens are prematurely converted to their active forms inside the pancreatic cells and attack the pancreatic tissue^[2].

Flashcard 36

Question: What do transamination reactions transfer and yield? Answer: Transamination reactions transfer the α-amino group to the α-carbon atom of α-ketoglutarate, yielding an α-keto acid analog of the amino acid^[2].

Flashcard 37

Question: What are the reversibility and functional roles of transamination reactions? Answer: Reactions are freely reversible (∆G′ ≈ 0 kJ/mol) and effectively collect the amino groups from many amino acids in the form of L-glutamate^[2].

Flashcard 38

Question: What enzyme catalyzes the removal of α-amino groups? Answer: Aminotransferases (transaminases) catalyze the removal of the α-amino groups^[2].

Flashcard 39

Question: What is pyridoxal phosphate (PLP) and its role in transamination? Answer: Pyridoxal phosphate is the coenzyme form of pyridoxine (vitamin B6) that participates in the transfer of α-amino groups to α-ketoglutarate^[2].

Flashcard 40

Question: How do aminotransferases in cells differ in specificity? Answer: Cells contain different types that differ in their specificity for the L-amino acid, and many are specific for α-ketoglutarate as the amino group acceptor^[2].

Flashcard 41

Question: What are the functions of PLP (aldehyde form) and pyridoxamine phosphate (aminated form)? Answer: PLP (aldehyde form) accepts an amino group, while pyridoxamine phosphate (aminated form) donates its amino group to an α-keto acid^[2].

Flashcard 42

Question: What is the general role of PLP as a prosthetic group in aminotransferases? Answer: Pyridoxal phosphate (PLP) is used as a prosthetic group by all aminotransferases; it carries amino groups at the active site^[2].

Flashcard 43

Question: What three types of reactions are facilitated by PLP? Answer: Reactions facilitated by PLP are transamination, racemization, and decarboxylation^[2].

Flashcard 44

Question: In what forms does mitochondrial NH4+ originate from α-amino acids? Answer: NH4+ in the mitochondria comes from many different α-amino acids in the form of the amino group of L-glutamate or the amide nitrogen of glutamine^[2].

Flashcard 45

Question: What combined enzymatic action produces transdeaminases? Answer: Transdeaminases result from the combined action of an aminotransferase and glutamate dehydrogenase^[2].

Flashcard 46

Question: What is glutamate dehydrogenase (GDH) and where does it operate? Answer: Glutamate dehydrogenase (GDH) is a crucial enzyme operating at the intersection of carbon and nitrogen metabolism in prokaryotes and eukaryotes, operating in the mitochondrial matrix^[2].

Flashcard 47

Question: What reaction is catalyzed by glutamate dehydrogenase? Answer: Glutamate dehydrogenase catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia^[2].

Flashcard 48

Question: What are the metabolic fates of α-ketoglutarate produced by GDH? Answer: α-ketoglutarate can enter the citric acid cycle or be used for glucose synthesis^[2].

Flashcard 49

Question: What electron acceptors and allosteric modulators regulate glutamate dehydrogenase (GDH)? Answer: GDH can use either NAD+ or NADP+, is positively modulated by ADP (signaling low glucose levels), and is negatively modulated by GTP (signaling high levels of α-ketoglutarate)^[2].

Flashcard 50

Question: What reaction is catalyzed by glutamine synthetase? Answer: Glutamine synthetase catalyzes the combination of free ammonia with glutamate to yield glutamine, requiring ATP and being critical to transport toxic ammonia to the liver^[4].

Flashcard 51

Question: What reaction is catalyzed by glutaminase? Answer: Glutaminase catalyzes the conversion of glutamine to glutamate and NH4+^[4].

Flashcard 52

Question: How is ammonia transported from skeletal muscles to the liver? Answer: Alanine transports ammonia from skeletal muscles to the liver^[4].

Flashcard 53

Question: What three products are produced by skeletal muscles during nitrogen catabolism? Answer: Skeletal muscles produce pyruvate, lactate, and ammonia^[4].

Flashcard 54

Question: How does alanine aminotransferase function in the Glucose-Alanine Cycle? Answer: Alanine aminotransferase interconverts pyruvate and alanine via transamination with glutamate, allowing ammonia to be excreted and pyruvate to produce glucose returned to muscle^[4].

Flashcard 55

Question: Why is free ammonia toxic, particularly to astrocyte cells in the brain? Answer: Free ammonia is toxic to the brain because NH4+ competes with K+ for transport into astrocyte cells through Na+K+ ATPase, resulting in elevated extracellular [K+]^[4][5].

Flashcard 56

Question: What is NKCC1 and how does excess extracellular K+ alter neuronal response? Answer: NKCC1 is a symporter transporting Na+, K+, and Cl-; excess Cl- from excess K+ alters neuronal response to the neurotransmitter GABA^[5].

Flashcard 57

Question: What is the urea cycle definition and pathway summary? Answer: The urea cycle is the pathway by which ammonia deposited in hepatocyte mitochondria is converted to urea, which enters the bloodstream and is excreted into urine^[5].

Flashcard 58

Question: How many steps comprise the urea cycle and how are the enzymes organized? Answer: Urea is produced from ammonia in five steps involving enzymes clustered in metabolons (temporary structural-functional complexes formed between sequential enzymes of the pathway)^[5].

Flashcard 59

Question: What reaction is catalyzed by carbamoyl phosphate synthetase I? Answer: Carbamoyl phosphate synthetase I catalyzes the formation of carbamoyl phosphate from NH4+ and CO2 (as HCO3-), requiring 2 ATP and occurring in the mitochondrial matrix^[5].

Flashcard 60

Question: How does the first nitrogen enter the urea cycle? Answer: The first nitrogen enters from ammonia in the reaction catalyzed by carbamoyl phosphate synthetase I, which has two activation steps requiring ATP^[6].

Flashcard 61

Question: What reaction is catalyzed by ornithine transcarbamoylase? Answer: Ornithine transcarbamoylase catalyzes the formation of citrulline and Pi from ornithine and carbamoyl phosphate^[6].

Flashcard 62

Question: Where does citrulline move after its synthesis? Answer: Citrulline passes from the mitochondrion to the cytosol^[6].

Flashcard 63

Question: What reaction is catalyzed by argininosuccinate synthetase? Answer: Argininosuccinate synthetase catalyzes the condensation of the amino group of aspartate and the ureido group of citrulline to form argininosuccinate, requiring ATP and using a citrullyl-AMP intermediate^[6].

Flashcard 64

Question: How does the second nitrogen enter the urea cycle? Answer: The second nitrogen enters from ammonia in the reaction catalyzed by argininosuccinate synthetase, having two activation steps^[6].

Flashcard 65

Question: What reaction is catalyzed by argininosuccinase? Answer: Argininosuccinase catalyzes the reversible cleavage of argininosuccinate to form arginine and fumarate^[6].

Flashcard 66

Question: What happens to fumarate formed by argininosuccinase? Answer: Fumarate is converted to malate and joins the pool of citric acid cycle intermediates^[6].

Flashcard 67

Question: What reaction is catalyzed by arginase? Answer: Arginase catalyzes the cleavage of arginine to form urea and ornithine; ornithine is transported into the mitochondrion to initiate another round^[6].

Flashcard 68

Question: Which transporters facilitate communication between the citric acid and urea cycles? Answer: Communication depends on the malate–α-ketoglutarate transporter, glutamate-aspartate transporter, and glutamate-OH- transporter^[6].

Flashcard 69

Question: What shunt links the citric acid and urea cycles? Answer: The aspartate-argininosuccinate shunt links the citric acid and urea cycles, connecting the fates of amino groups and carbon skeletons^[6][7].

Flashcard 70

Question: How is NADH brought into the mitochondrion in connection with the urea cycle? Answer: The urea and citric acid cycles are closely tied to an additional process that brings NADH, in the form of reducing equivalents, into the mitochondrion^[7].

Flashcard 71

Question: What is the biological significance of aspartate as a nitrogen donor? Answer: Aspartate as a nitrogen donor is one of the two common ways to introduce amino groups into biomolecules^[7].

Flashcard 72

Question: What is the net overall equation for the urea cycle in isolation? Answer: In isolation, the urea cycle requires four high-energy phosphate groups: 2NH4+ + HCO3- + 3ATP4- + H2O → urea + 2ADP3- + 4Pi2- + AMP2- + 2H+^[3][7].

Flashcard 73

Question: How are the 4 high-energy ATP equivalents consumed in urea synthesis accounted for? Answer: Two ATPs are utilized for carbamoyl phosphate synthesis, and one ATP is converted to AMP and PPi to produce argininosuccinate (equivalent to 2 ATP), totaling 4 ATP consumed^[3].

Flashcard 74

Question: At what two levels is the activity of the urea cycle regulated? Answer: Regulated at the level of enzyme synthesis for carbamoyl phosphate synthetase I and the four urea cycle enzymes, and by allosteric regulation of carbamoyl phosphate synthetase I^[7].

Flashcard 75

Question: How is N-acetylglutamate synthesized? Answer: Glutamate levels rise during amino acid breakdown and acetyl-CoA is abundant during energy production; their combination stimulates N-acetylglutamate synthase to form N-acetylglutamate from acetyl-CoA and glutamate^[7].

Flashcard 76

Question: What metabolic signal is provided by N-acetylglutamate and how does it act? Answer: N-acetylglutamate signals that the body needs ammonia detoxification and allosterically activates carbamoyl phosphate synthetase I to initiate the urea cycle^[7].

Flashcard 77

Question: Why are protein-free diets not a treatment option for urea cycle enzyme defects? Answer: Protein-free diets are not an option because essential amino acids cannot be synthesized by humans and must be obtained in the diet^[3].

Flashcard 78

Question: What role do benzoate and phenylbutyrate play in treating urea cycle enzyme deficiencies? Answer: Benzoate and phenylbutyrate serve as nitrogen scavengers, helping to reduce toxic levels of ammonia in the blood^[3].

Flashcard 79

Question: What specific amino acids combine with metabolized benzoate and phenylbutyrate? Answer: Benzoate is metabolized and combines with glycine, while phenylbutyrate is metabolized and combines with glutamine^[3].

Flashcard 80

Question: What percentage of human energy production is derived from amino acid breakdown? Answer: Breakdown of amino acids accounts for 10-15% of human energy production^[3].

Flashcard 81

Question: What six major products are formed by the convergence of the 20 amino acid catabolic pathways? Answer: The 20 catabolic pathways converge to form pyruvate, acetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate^[3].

Flashcard 82

Question: What are ketogenic amino acids and which seven amino acids belong to this category? Answer: Ketogenic amino acids yield ketone bodies in the liver: phenylalanine, tyrosine, isoleucine, leucine, tryptophan, threonine, and lysine^[3].

Flashcard 83

Question: What are glucogenic amino acids and which amino acids belong to this category? Answer: Glucogenic amino acids can be converted to glucose and glycogen; all amino acids except lysine and leucine are glucogenic^[3].

Flashcard 84

Question: What three cofactors play major roles in one-carbon transfers during amino acid catabolism? Answer: Biotin (transfers CO2), tetrahydrofolate (transfers intermediate oxidation states), and S-adenosylmethionine (transfers methyl groups)^[3].

Flashcard 85

Question: What is the chemical composition and origin of tetrahydrofolate (H4 folate)? Answer: Tetrahydrofolate consists of substituted pterin (6-methylpterin), p-aminobenzoate, and glutamate moieties, synthesized in bacteria^[3].

Flashcard 86

Question: What is folate and where do one-carbon groups attach on tetrahydrofolate? Answer: Folate is the oxidized form of tetrahydrofolate; the one-carbon group is bonded to N-5, N-10, or both^[3].

Flashcard 87

Question: What is the primary amino acid source of one-carbon units donated to THF? Answer: Serine is a major source of one-carbon units donated to THF, while other sources include glycine and formate^[3].

Flashcard 88

Question: What enzyme catalyzes the conversion of serine to glycine and what entry point product is formed? Answer: Serine hydroxymethyl transferase catalyzes the conversion of serine to glycine, forming N-5,10 methylene THF, a key entry point for carbon units into one-carbon metabolism^[3].

Flashcard 89

Question: What essential biological processes involve THF? Answer: THF is involved in the synthesis of amino acids and nucleic acids, and plays a role in DNA methylation, affecting gene expression and repair^[3].

Flashcard 90

Question: How is S-adenosylmethionine (SAM) synthesized? Answer: Methionine adenosyl transferase catalyzes the synthesis of S-adenosylmethionine from ATP and methionine, driven by hydrolysis of triphosphate^[3][8].

Flashcard 91

Question: Why is S-adenosylmethionine the preferred cofactor for methyl group transfers over N5-methyltetrahydrofolate? Answer: S-adenosylmethionine's methyl group is ~1000x more reactive than the methyl group of N5-methyltetrahydrofolate^[8].

Flashcard 92

Question: What compound is formed when SAM transfers its methyl group to an acceptor? Answer: S-adenosylhomocysteine is formed when the methyl group from S-adenosylmethionine is transferred to an acceptor^[8].

Flashcard 93

Question: What anemias occur in vitamin B12 deficiency and what causes the erythrocyte defects? Answer: B12 deficiency causes pernicious anemia (traced to methionine synthase reaction) and megaloblastic anemia; erythrocyte defects are due to depletion of N5,N10-methylenetetrahydrofolate^[8].

Flashcard 94

Question: What is 5,6,7,8-tetrahydrobiopterin (BH4) and what enzymes require it? Answer: BH4 is an essential cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and nitric oxide synthases (NOSs)^[8].

Flashcard 95

Question: Which six amino acids are converted in whole or in part to pyruvate? Answer: Alanine, tryptophan, cysteine, serine, glycine, and threonine are converted in whole or in part to pyruvate^[8].

Flashcard 96

Question: What are the two catabolic fates of pyruvate produced from amino acid breakdown? Answer: Pyruvate is either converted to acetyl-CoA for oxidation via the citric acid cycle or oxaloacetate to enter gluconeogenesis^[8].

Flashcard 97

Question: Which amino acids yield acetyl-CoA via acetoacetyl-CoA, and which yield acetyl-CoA directly? Answer: Leucine, lysine, phenylalanine, tyrosine, and tryptophan yield acetyl-CoA via acetoacetyl-CoA; isoleucine, leucine, threonine, and tryptophan form acetyl-CoA directly^[8].

Flashcard 98

Question: What three inborn errors of metabolism result from enzymatic defects in phenylalanine/tyrosine degradation? Answer: Phenylketonuria (PKU), Alkaptonuria, and Albinism^[8].

Flashcard 99

Question: What enzyme deficiency causes Phenylketonuria (PKU) and how is it characterized and treated? Answer: PKU is characterized by excessive phenylpyruvate in urine due to phenylalanine hydroxylase deficiency; treated with dietary intervention to prevent severe mental retardation^[8].

Flashcard 100

Question: What enzyme deficiency causes Alkaptonuria, and what derived pigment is deficient in Albinism? Answer: Alkaptonuria results from homogentisate dioxygenase deficiency (excreting homogentisate); Albinism is characterized by deficiency/lack of melanin derived from tyrosine/DOPA^[8].

Flashcard 101

Question: Which five amino acids are degraded to α-ketoglutarate via glutamate? Answer: Arginine, glutamate, glutamine, histidine, and proline are degraded to α-ketoglutarate via glutamate^[8][9].

Flashcard 102

Question: Which three amino acids are converted via propionyl-CoA to succinyl-CoA? Answer: Valine, isoleucine, and methionine are converted via propionyl-CoA to succinyl-CoA for entry into the citric acid cycle^[9].

Flashcard 103

Question: Where are branched-chain amino acids degraded and why? Answer: Valine, leucine, and isoleucine are degraded only in extrahepatic tissues (muscle, adipose, kidney, brain) because the aminotransferase is absent in the liver^[9].

Flashcard 104

Question: What are the first three common steps in branched-chain amino acid degradation? Answer: The first three steps follow a common pathway with identical reactions: transamination, oxidative decarboxylation, and dehydrogenation^[9].

Flashcard 105

Question: What enzyme complex catalyzes oxidative decarboxylation of branched-chain α-keto acids and how is it regulated? Answer: Branched-chain α-keto acid dehydrogenase complex catalyzes oxidative decarboxylation; it is regulated by covalent modification and is inactive when phosphorylated^[9].

Flashcard 106

Question: What accumulates in Maple Syrup Urine Disease and how is it treated? Answer: The three branched-chain α-keto acids and their precursor amino acids accumulate in blood and spill into urine; treated by rigid control of the diet^[9].

Flashcard 107

Question: Which two amino acids are degraded to oxaloacetate and what enzymes catalyze their breakdown? Answer: Asparagine and aspartate; asparaginase hydrolyzes asparagine to aspartate, and aspartate aminotransferase transaminates aspartate with α-ketoglutarate^[9].

Flashcard 108

Question: What molecule is produced if kynurenine is not metabolized to α-ketoadipate during tryptophan breakdown? Answer: If kynurenine is not metabolized to α-ketoadipate, quinolinate can be produced^[9].

Flashcard 109

Question: What essential cofactors and pathological conditions are linked to the kynurenine pathway of tryptophan degradation? Answer: The kynurenine pathway supports biogenesis of niacin/vitamin B3 and NAD via quinolinate; it has links with neurodegenerative diseases, tumor proliferation, inflammation, and depression