PHRM246 Amino Acid Metabolism

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Questions and Answers

Which enzyme is primarily responsible for cleaving chymotrypsinogen to chymotrypsin?

Enteropeptidase

Pepsin

Aminopeptidase

Trypsin (correct)

What is the primary consequence of hyper-ammonemia?

Enhanced amino acid absorption

Increased urinary output

Increased protein synthesis

Severe neurological defects (correct)

Which amino acids are classified as ketogenic in humans?

Leucine and Lysine (correct)

Isoleucine and Threonine

Valine and Phenylalanine

Alanine and Glutamine

What is the indicator for liver disease based on blood levels?

Aminotransferases Signup and view all the answers

Which amino acid can be synthesized from phenylalanine?

Tyrosine Signup and view all the answers

Which process involves the conversion of NH4+ and bicarbonate into carbamoyl phosphate?

Urea Cycle Signup and view all the answers

What role does GABA play in the body?

It serves as an inhibitory neurotransmitter. Signup and view all the answers

Which process is primarily responsible for removing ammonia from the body?

Urea cycle Signup and view all the answers

What physiological role does nitric oxide (NO) primarily serve?

Vasodilation Signup and view all the answers

What is the consequence of congestive heart failure on renal function?

Low blood pressure and reduced renal filtration Signup and view all the answers

Which enzyme is responsible for converting arginine to nitric oxide?

Nitric oxide synthase Signup and view all the answers

What role does sarcosine play in medical research?

Possible biomarker for prostate cancer Signup and view all the answers

Which statement about the formation of serine is true?

It involves glycolysis and other metabolic processes. Signup and view all the answers

What does sildenafil (Viagra) block to prolong the effect of nitric oxide?

Phosphodiesterase-5 Signup and view all the answers

What compounds are primarily removed during hemo-dialysis from the blood?

Urea and waste products Signup and view all the answers

Which amino acid is formed from the conversion of serine and is important in various biosynthetic processes?

Glycine Signup and view all the answers

What role does nitric oxide play in the body beyond vasodilation?

It acts as a neurotransmitter. Signup and view all the answers

Which process is directly inhibited by high levels of pyruvate when forming serine?

Transaminase activity Signup and view all the answers

What is the consequence of tyramine intake in individuals taking MAO inhibitors?

Hypertensive crisis Signup and view all the answers

Which metabolic pathway terminates the activity of catecholamines?

Catechol-O-Methyl Transferase (COMT) pathway Signup and view all the answers

What is the main cause of alkaptonuria?

Deficiency of homogentisate dioxygenase Signup and view all the answers

Where is serotonin primarily synthesized in the body?

Brain Signup and view all the answers

What is a significant risk associated with L-Tryptophan supplements?

Eosinophilia-myalgia syndrome (EMS) Signup and view all the answers

Which of the following conditions is characterized by a deficiency of cystathionine b-synthase?

Homocysteinuria Signup and view all the answers

What role does dietary folate play in homocysteine metabolism?

Enhances conversion of homocysteine to methionine Signup and view all the answers

Which compound is a byproduct of creatine metabolism and used as a marker for kidney function?

Creatinine Signup and view all the answers

Which of the following is an essential amino acid involved in the synthesis of histamine?

Histidine Signup and view all the answers

What is the primary amino acid precursor for the synthesis of taurine?

Cysteine Signup and view all the answers

What is one of the main roles of polyamines like spermidine and spermine in the cell?

Binding to nucleic acids Signup and view all the answers

Which enzyme is responsible for the conversion of phenylalanine to tyrosine?

Phenylalanine monooxygenase Signup and view all the answers

What is the impact of high blood levels of homocysteine on health?

Higher risk of cardiovascular disease Signup and view all the answers

What is the principal physiological role of creatine in muscle tissues?

Energy storage Signup and view all the answers

Which of the following statements about phenylketonuria (PKU) is true?

It is a deficiency of phenylalanine hydroxylase. Signup and view all the answers

What is the primary treatment method for conditions associated with elevated phenylalanine levels?

Limit phenylalanine intake Signup and view all the answers

Which neurotransmitter is synthesized from DOPA?

Norepinephrine Signup and view all the answers

In the context of the biochemical pathway mentioned, what is the role of tyrosine hydroxylase?

Converts tyrosine to DOPA Signup and view all the answers

Which of the following statements is accurate regarding screening for phenylketonuria?

Screening is mandated in all states Signup and view all the answers

What is the effect of Carbidopa in the treatment of Parkinsonism?

It blocks the metabolism of L-DOPA to dopamine Signup and view all the answers

Which compound is a product of the transamination of phenylalanine?

Phenylpyruvate Signup and view all the answers

What condition is associated with the loss of neurons in the basal ganglia?

Parkinsonism Signup and view all the answers

Which of the following is NOT a neurotransmitter mentioned in the content?

GABA Signup and view all the answers

Which of these pathways involves catecholamine biosynthesis?

Formation of catecholamines from phenylalanine Signup and view all the answers

What is a major consequence of untreated phenylketonuria?

Reduced cognitive function Signup and view all the answers

Study Notes

Dynamics of Protein and Amino Acid Metabolism

Dietary proteins undergo digestion to yield amino acids.
Amino acids are transported through the blood to cells for protein synthesis.
Proteins are degraded in proteasomes, tagged with ubiquitin for identification.

Digestion of Proteins

Occurs in the stomach via pepsinogen (activated to pepsin at pH 2) and enteropeptidase.
In the small intestine, trypsinogen activates to trypsin, which cleaves several zymogens:
- Chymotrypsinogen to chymotrypsin
- Proelastase to elastase
- Procarboxypeptidase to carboxypeptidase.
Aminopeptidases aid in digestion from intestinal epithelia.

Amino Acid Transport and Absorption

Amino acids and oligopeptides are absorbed in the intestinal lumen.
Transport proteins and peptidases facilitate absorption into the bloodstream.

Incorporation of Ammonium (NH4+)

Ammonium ions combine with bicarbonate and ATP to form carbamoyl phosphate via Carbamoyl Phosphate Synthase I (CPS-I).
In the mitochondria, α-ketoglutarate and NH4+ can yield glutamate through dehydrogenase mechanisms.
Glutamate can further form glutamine through Glutamine Synthase.

Biosynthesis of Amino Acids

Transamination processes interchange amino acids and α-keto acids, utilizing pyridoxal phosphate (PLP) for conversion.
Enzymes like the alanine and aspartate transferases are critical for assessing liver health.

Classification of Amino Acids

Essential Amino Acids: Cannot be synthesized, must be obtained from diet (e.g., arginine, lysine, methionine).
Non-Essential Amino Acids: Can be synthesized in the body from α-keto acids (e.g., alanine, glutamine).
Glucogenic Amino Acids: Can be converted into glucose precursors.
Ketogenic Amino Acids: Converted into acetyl CoA or acetoacetyl CoA.

Urea Cycle and Ammonium Metabolism

Primarily occurs in the liver; excretion by kidneys removes excess ammonia.
Deficiencies in urea cycle enzymes lead to hyperammonemia and neurological issues in neonates.
Elevated blood urea nitrogen (BUN) indicates amino acid catabolism and kidney function.

Formation and Role of Nitric Oxide

Synthesized from arginine via nitric oxide synthase and is crucial for vasodilation.
Implicated in various physiological processes and therapeutic applications (e.g., sildenafil).

Conversion Pathways for Amino Acids

Conversion from serine to glycine is facilitated by serine hydroxymethyltransferase, a key step in purine and heme biosynthesis.
Sarcosine, a derivative of glycine, is studied as a potential prostate cancer biomarker.

Important Enzymes and Processes

Glutamate decarboxylase converts glutamate to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.
Urea formation involves multiple enzymatic steps, converting ammonia into urea for detoxification and excretion.### B12-Dependent Pathways and Amino Acids
Homocysteine, derived from methionine, can lead to serious health issues when elevated, including cardiovascular disease.
Homocysteinuria results from cystathionine beta-synthase deficiency, presenting with dislocated lenses, mental retardation, and osteoporosis.
Methionine metabolism involves the conversion of methionine to S-adenosyl methionine (SAM), a key methyl donor in biochemical reactions.

Polyamine Biosynthesis

Polyamines, such as spermidine and spermine, are found in all living cells and bind nucleic acids, though their exact roles remain unclear.
Ornithine decarboxylase is essential for polyamine biosynthesis and can be inhibited by a-Difluoromethyl-ornithine (DFMO) for treating specific infections.

Creatine and Creatinine

Creatine is a dietary supplement used for athletic performance enhancement, while creatinine is a waste product measurable in urine, reflecting muscle mass.
The creatinine clearance test assesses kidney function by comparing urine and blood creatinine levels, crucial for drug dosing in patients with renal impairment.

Histidine Metabolism and Histamine

Histamine is formed from histidine via histidine decarboxylase and is released by mast cells during allergic responses.
H1 and H2 histamine receptors are targeted by various medications: H1 blockers (like Diphenhydramine) and H2 blockers (like Cimetidine), affecting allergy and gastric acid secretion.

Phenylalanine and Tyrosine

Phenylalanine, an essential amino acid, is converted into tyrosine in the body, which is considered non-essential despite being derived from phenylalanine.
Phenylketonuria (PKU) occurs due to phenylalanine hydroxylase deficiency, leading to severe developmental issues; newborn screening for PKU has been mandated.

Catecholamine Biosynthesis

Catecholamines such as dopamine, norepinephrine, and epinephrine are synthesized from tyrosine and play critical roles in the nervous system.
L-DOPA is used in the treatment of Parkinson's disease to replenish lost dopamine in the brain, aided by carbidopa to enhance effectiveness.

Tyramine and MAO Inhibitors

Tyramine can trigger a hypertensive crisis in individuals on monoamine oxidase (MAO) inhibitors due to increased norepinephrine release.

Catechol-O-Methyl Transferase (COMT)

COMT terminates catecholamine activity in the cytoplasm.
Active catecholamines are converted into inactive metabolites by COMT, alongside MAO.
COMT inhibitors, such as tolcapone, are beneficial for treating Parkinson’s disease.

Homogentisic Acid Formation

Transamination process converts tyrosine into p-hydroxyphenylpyruvate.
Homogentisate dioxygenase deficiency leads to alkaptonuria, a condition characterized by dark urine due to oxidation of homogentisic acid.
Individuals are typically asymptomatic during childhood but may develop arthritis in adulthood.

Melanin Formation

Tyr hydroxylase catalyzes the conversion of tyrosine to DOPA, which further transforms into melanin.
Melanin serves as a protective pigment in skin, eyes, and hair against sunlight.
Albinism results from a genetic deficiency of tyrosinase, critical for melanin synthesis.

Tryptophan Metabolism: Serotonin Formation

Tryptophan is converted to serotonin (5-hydroxytryptamine, 5-HT) via hydroxylation and decarboxylation processes.

Serotonin

Serotonin functions as a neurotransmitter and influences mood, sleep, and appetite in the brain.
Found in platelets, serotonin aids in aggregation and vasoconstriction.
Major storage site of serotonin is within enterochromaffin cells in the gastrointestinal tract.
Therapeutic drugs targeting serotonin include SSRIs for depression, alongside treatments for migraine, schizophrenia, and obsessive-compulsive disorders.
Some hallucinogens, like LSD, act as serotonin agonists, influencing mood and perception.

L-Tryptophan

L-Tryptophan, a food supplement, is associated with serotonin enhancement but is linked to Eosinophilia-myalgia syndrome (EMS) with symptoms like muscle pain, swelling, and rashes due to impurities leading to hundreds of cases and several fatalities.

Serotonin Metabolism: 5-HIAA

5-Hydroxyindole acetic acid (5-HIAA) is a urinary metabolite of serotonin.
Carcinoid tumors result in excessive 5-HIAA excretion, indicating the presence of malignant gastrointestinal tumors.

Serotonin Metabolism: Melatonin

Melatonin, synthesized primarily in the pineal gland, controls sleep cycles and is influenced by light.
Melatonin can induce skin lightening and suppress ovarian function, with potential uses in treating sleep disorders.

Tryptophan Metabolism: Nicotinic Acid Biosynthesis

Tryptophan undergoes several steps to form nicotinic acid (Niacin), an essential metabolite linked to energy metabolism and cellular function.
Niacin is crucial for the synthesis of nicotinamide adenine dinucleotide (NAD), a key coenzyme in metabolic processes.

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Description

This quiz covers the dynamics of protein and amino acid metabolism, focusing on the digestion of dietary proteins into amino acids and their transport to cells. It also explores protein synthesis, functional proteins, and the degradation of proteins in proteasomes. Enhance your understanding of these essential biological processes.