BCM 2 exam 2 study guide final

What is the coenzyme involved in transaminase reactions?

Pyridoxal phosphate (PLP), the coenzyme form of vitamin B6.

What is the underlying role of PLP in transamination?

PLP acts as an intermediate carrier of amino groups at the active site of aminotransferases. Its aminated form is pyridoxamine phosphate (PMP).

What is the overall mechanism of a PLP-dependent transamination?

Amino acid + α-ketoglutarate ⇌ α-keto acid + glutamate. PLP accepts the amino group from the amino acid to become PMP, then PMP transfers that amino group to α-ketoglutarate, regenerating PLP.

What other reactions can PLP facilitate besides transamination?

Racemization and decarboxylation.

What is the function of N-acetylglutamate?

N-acetylglutamate is the essential allosteric activator of carbamoyl phosphate synthetase I (CPS I).

How does N-acetylglutamate regulate the urea cycle?

It activates CPS I, the enzyme that catalyzes formation of carbamoyl phosphate and controls entry of NH4+ into the urea cycle.

How is N-acetylglutamate produced and how does it regulate the urea cycle?

Glutamate + acetyl-CoA → N-acetylglutamate, catalyzed by N-acetylglutamate synthase. Arginine activates N-acetylglutamate synthase → ↑ N-acetylglutamate → activation of CPS I → ↑ urea-cycle flux.

What determines steady-state N-acetylglutamate levels in mammals?

Glutamate, acetyl-CoA, and arginine. Arginine activates N-acetylglutamate synthase and therefore indirectly activates the urea cycle.

What processes are associated with the glucose-alanine cycle?

Muscle exports nitrogen and pyruvate as alanine to the liver; the liver disposes of the nitrogen as urea and returns the carbon as glucose.

What is the purpose of the glucose-alanine cycle?

It transports amino nitrogen from skeletal muscle to the liver while allowing the pyruvate carbon skeleton to be recycled into glucose.

What is the pathway of the glucose-alanine cycle?

Muscle: amino acids → glutamate; glutamate + pyruvate ⇌ α-ketoglutarate + alanine via alanine aminotransferase → alanine enters blood → liver: alanine + α-ketoglutarate ⇌ pyruvate + glutamate → glutamate releases NH4+ for urea synthesis; pyruvate → gluconeogenesis → glucose → blood → muscle.

Which two major metabolic processes are coupled by the glucose-alanine cycle?

Amino acid catabolism/nitrogen disposal and gluconeogenesis.

What is the function of glutamate dehydrogenase in amino acid metabolism?

It reversibly converts glutamate to α-ketoglutarate and NH4+, linking amino-group metabolism to the citric acid cycle.

Why is glutamate dehydrogenase important for nitrogen disposal?

Transamination collects amino groups in glutamate, and GDH releases glutamate's amino group as NH4+ in liver mitochondria for urea synthesis.

What reaction is catalyzed by glutamate dehydrogenase?

Glutamate + NAD(P)+ + H2O ⇌ α-ketoglutarate + NH4+ + NAD(P)H + H+. GDH operates in the mitochondrial matrix and can use NAD+ or NADP+.

How is glutamate dehydrogenase regulated?

ADP positively modulates GDH, whereas GTP negatively modulates it. The α-ketoglutarate produced can enter the citric acid cycle or be used for glucose synthesis. Ch18 Candas Lecture (1)

How is the energy demand of the urea cycle compensated?

Fumarate produced by the urea cycle is converted to malate and then oxaloacetate, generating NADH that can yield ATP through oxidative phosphorylation.

Why is the energetic cost of the urea cycle lower than its ATP consumption alone suggests?

The aspartate-argininosuccinate shunt links the urea and citric acid cycles, and oxidation of malate to oxaloacetate produces NADH, recovering some of the energy spent by the urea cycle.

How does the aspartate-argininosuccinate shunt compensate for urea-cycle energy use?

Argininosuccinate → arginine + fumarate → malate → oxaloacetate. Malate dehydrogenase converts malate + NAD+ → oxaloacetate + NADH + H+; oxaloacetate can then be transaminated to aspartate and return to the urea cycle.

How much energy does the urea cycle consume directly?

3 ATP molecules are consumed, but 4 high-energy phosphate bonds are used because one ATP is converted to AMP + PPi. The textbook notes that cycle interconnections reduce the energetic cost. Chapter 18 textbook(1)

What compounds are excreted for the elimination of nitrogen in mammals?

Urea is the major nitrogenous excretory product in mammals.

Why do mammals primarily convert ammonia to urea?

Free ammonia is toxic, so ureotelic mammals detoxify amino nitrogen by converting it into relatively nontoxic urea.

What is the general route for nitrogen excretion in mammals?

Amino acids → amino groups collected largely as glutamate, glutamine, or alanine → liver → NH4+ → carbamoyl phosphate → urea cycle → urea → blood → kidneys → urine.

How do the major nitrogenous waste strategies differ among animals?

Ammonotelic animals excrete ammonia, ureotelic animals such as mammals excrete urea, and uricotelic animals excrete uric acid. Water availability is a major determinant. Ch18 Candas Lecture (1)

What is phenylketonuria (PKU)?

PKU is an inherited defect in conversion of phenylalanine to tyrosine, usually caused by phenylalanine hydroxylase deficiency.

What metabolic reaction is defective in classical phenylketonuria?

Phenylalanine → tyrosine is impaired because phenylalanine hydroxylase is deficient.

What is the normal phenylalanine hydroxylase reaction?

Phenylalanine + O2 + tetrahydrobiopterin (BH4) → tyrosine + H2O + dihydrobiopterin, catalyzed by phenylalanine hydroxylase.

Why does phenylalanine accumulate in PKU?

Loss of phenylalanine hydroxylase activity prevents normal conversion of phenylalanine to tyrosine, causing phenylalanine to accumulate.

How does the urea cycle support the Krebs cycle?

The urea cycle produces fumarate, which can be converted to malate and oxaloacetate, both citric acid cycle intermediates.

What is the metabolic connection between the urea cycle and the citric acid cycle?

The aspartate-argininosuccinate shunt connects the cycles through fumarate, malate, oxaloacetate, and aspartate.

Trace the connection between the urea cycle and Krebs cycle.

Argininosuccinate → arginine + fumarate → fumarate → malate → oxaloacetate → aspartate; aspartate reenters the urea cycle by combining with citrulline → argininosuccinate.

What useful products arise from the fumarate generated by the urea cycle?

Fumarate supplies a citric acid cycle intermediate, and its conversion through malate to oxaloacetate generates NADH and regenerates oxaloacetate for aspartate formation. Chapter 18 textbook(1)

Which compound directly donates a nitrogen atom for urea formation during the urea cycle?

Aspartate directly donates the second nitrogen of urea.

Where do the two nitrogen atoms of urea originate?

One nitrogen comes from NH4+ and the second comes from aspartate.

How do the two nitrogens enter the urea cycle?

NH4+ → carbamoyl phosphate via CPS I → citrulline; aspartate then combines with citrulline → argininosuccinate. Both nitrogens are ultimately incorporated into urea.

At what step does aspartate donate its nitrogen to the urea cycle?

Citrulline + aspartate + ATP → argininosuccinate + AMP + PPi, catalyzed by argininosuccinate synthetase. Chapter 18 textbook(1)

What is the metabolic defect in maple syrup urine disease?

Deficiency of the branched-chain α-keto acid dehydrogenase complex, impairing degradation of leucine, isoleucine, and valine.

Why does branched-chain α-keto acid dehydrogenase deficiency cause maple syrup urine disease?

The branched-chain amino acids are transaminated, but their resulting α-keto acids cannot undergo normal oxidative decarboxylation.

Where does the defective step occur in branched-chain amino acid catabolism in MSUD?

Leucine/isoleucine/valine → corresponding branched-chain α-keto acids by transamination → ✕ branched-chain α-keto acid dehydrogenase complex → downstream acyl-CoA derivatives.

Which three amino acids are improperly degraded in maple syrup urine disease?

Leucine, isoleucine, and valine.

Where does urea synthesis take place in mammals?

In the liver, with the first two urea-cycle reactions in mitochondria and the remaining reactions in the cytosol.

Why does the urea cycle span two cellular compartments?

Carbamoyl phosphate and citrulline are produced in the mitochondrial matrix, after which citrulline is transported to the cytosol for the remaining reactions.

What is the compartmental organization of the urea cycle?

Mitochondria: NH4+ + HCO3− → carbamoyl phosphate → citrulline. Citrulline exits to cytosol. Cytosol: citrulline → argininosuccinate → arginine → urea + ornithine. Ornithine returns to mitochondria.

Which organ is specialized for converting excess amino nitrogen into urea?

The liver.

Catabolism of which amino acids yields pyruvate?

Alanine, cysteine, glycine, serine, threonine, and tryptophan.

Why are amino acids that yield pyruvate considered glucogenic?

Pyruvate can be converted to oxaloacetate and used for gluconeogenesis, allowing their carbon skeletons to contribute to glucose synthesis.

What is the pathway by which pyruvate-producing amino acids can contribute to glucose?

Amino acid → pyruvate → oxaloacetate → phosphoenolpyruvate → gluconeogenesis → glucose.

Are leucine and lysine able to contribute net carbon to gluconeogenesis?

No. Leucine and lysine are exclusively ketogenic.

In amino acid catabolism, what is the first reaction and cofactor for many amino acids?

Transamination, using pyridoxal phosphate (PLP).

What happens during the initial transamination step of amino acid catabolism?

The α-amino group is transferred from an amino acid to α-ketoglutarate, producing glutamate and the corresponding α-keto acid.

What is the general transamination reaction?

L-amino acid + α-ketoglutarate ⇌ α-keto acid + L-glutamate, catalyzed by an aminotransferase using PLP.

Why is glutamate central to amino acid catabolism?

Transamination funnels amino groups from many different amino acids into glutamate, which can subsequently release NH4+ through glutamate dehydrogenase.

Which amino acid transports amino groups from muscle to the liver in a nontoxic form?

Alanine.

Why is alanine suited for transporting muscle nitrogen?

Muscle transfers amino groups to pyruvate to form alanine, allowing nitrogen and the pyruvate carbon skeleton to travel to the liver.

How is alanine formed and used in the glucose-alanine cycle?

Muscle: glutamate + pyruvate ⇌ α-ketoglutarate + alanine via alanine aminotransferase → blood → liver → alanine + α-ketoglutarate ⇌ pyruvate + glutamate → NH4+ → urea; pyruvate → glucose.

What happens to the carbon skeleton of alanine after it reaches the liver?

It becomes pyruvate, which is used to produce glucose; the glucose is returned to muscle. Ch18 Candas Lecture (1)

What is the function of tetrahydrofolate and its derivatives in metabolism?

Tetrahydrofolate (THF) carries and transfers one-carbon units in several oxidation states.

What types of groups are transferred by tetrahydrofolate derivatives?

One-carbon units, carried primarily at the N5 and/or N10 positions of tetrahydrofolate.

How does tetrahydrofolate participate in one-carbon metabolism?

One-carbon units enter the THF pool → are carried in forms such as N5,N10-methylene-THF and N5-methyl-THF → donated to reactions including nucleotide and methionine biosynthesis.

Why must tetrahydrofolate be regenerated?

THF must be regenerated so that it can continue accepting and transferring one-carbon units in metabolism.

Which enzyme is critical in activating protein-digesting zymogens in the small intestine?

Trypsin is the central activating protease; enteropeptidase initiates the cascade by converting trypsinogen to trypsin.

Why is trypsin central to pancreatic zymogen activation?

Trypsin activates additional trypsinogen as well as chymotrypsinogen, procarboxypeptidases, and proelastase.

What is the zymogen activation cascade in the small intestine?

Enteropeptidase: trypsinogen → trypsin → additional trypsinogen → trypsin; trypsin also activates chymotrypsinogen, procarboxypeptidases, and proelastase.

Why are pancreatic proteases synthesized as zymogens?

Inactive precursors protect the pancreas from self-digestion; pancreatic trypsin inhibitor provides additional protection.

What substrate is used to synthesize methionine by methionine synthase?

Homocysteine.

What does methionine synthase accomplish?

It transfers a methyl group to homocysteine, producing methionine.

What is the methionine synthase reaction?

N5-methyl-THF + homocysteine → THF + methionine, catalyzed by methionine synthase with vitamin B12 participating in methyl transfer.

Why are folate and vitamin B12 metabolism connected to methionine synthesis?

Methionine synthase transfers the methyl group of N5-methyl-THF to homocysteine through a vitamin B12-dependent reaction.

How many ATP are used in urea formation?

3 ATP molecules are used, corresponding to 4 high-energy phosphate bonds.

Why does the urea cycle use four high-energy phosphate bonds despite consuming only three ATP?

CPS I uses 2 ATP → 2 ADP, while argininosuccinate synthetase uses 1 ATP → AMP + PPi, equivalent to two high-energy phosphate bonds.

Where is ATP consumed during the urea cycle?

CPS I: NH4+ + HCO3− + 2 ATP → carbamoyl phosphate. Argininosuccinate synthetase: citrulline + aspartate + ATP → argininosuccinate + AMP + PPi.

What is the energetic accounting for one urea molecule?

3 ATP molecules are consumed, but 4 high-energy phosphate bonds are expended. The energetic cost is partially offset by NADH generation through the fumarate → malate → oxaloacetate connection.

Which two amino acids are exclusively ketogenic?

Leucine and lysine.

What does exclusively ketogenic mean?

Their carbon skeletons yield acetyl-CoA and/or acetoacetate and cannot contribute net carbon to glucose synthesis.

What is the metabolic fate of exclusively ketogenic amino acids?

Leucine and lysine → acetyl-CoA and/or acetoacetate → ketone-body or lipid metabolism, rather than net gluconeogenesis.

Which amino acids cannot contribute to gluconeogenesis?

Leucine and lysine. All other amino acids can contribute to gluconeogenesis when needed. Ch18 Candas Lecture (1)

What coenzyme is required for all transamination reactions?

Pyridoxal phosphate (PLP), derived from vitamin B6.

Why is PLP required for transamination?

PLP accepts an amino group to become pyridoxamine phosphate (PMP), which then donates that amino group to an α-keto acid.

What are the two functional forms involved in PLP-dependent transamination?

PLP (aldehyde form) accepts an amino group → PMP (aminated form); PMP donates its amino group to an α-keto acid → PLP is regenerated.

How is PLP associated with an aminotransferase active site?

PLP is a prosthetic group used by all aminotransferases and carries amino groups at the active site. Ch18 Candas Lecture (1)

What signals are associated with secretion of gastrin and secretin?

Dietary protein in the stomach stimulates gastrin secretion; low pH in the small intestine stimulates secretin secretion.

What is the physiological distinction between gastrin and secretin signaling?

Gastrin responds to dietary protein in the stomach, whereas secretin responds to acidic gastric contents reaching the duodenum.

What are the downstream responses associated with gastrin and secretin?

Dietary protein → gastrin → gastric glands secrete HCl and pepsinogen. Low pH in duodenum → secretin → pancreas secretes bicarbonate + water → neutralization of gastric acid.

What is the purpose of secretin-stimulated bicarbonate secretion?

It neutralizes gastric acid in the small intestine and maintains an optimal pH for digestion. Ch18 Candas Lecture (1)

Which amino acid metabolism is associated with serotonin production?

Tryptophan.

What is the relationship between tryptophan and serotonin?

Tryptophan is a precursor of serotonin. The textbook identifies serotonin as one of the biomolecules produced from tryptophan metabolism. Chapter 18 textbook(1)

What is the pathway from tryptophan to serotonin?

Tryptophan + O2 + BH4 → 5-hydroxytryptophan + H2O + BH2, catalyzed by tryptophan hydroxylase; 5-hydroxytryptophan → serotonin + CO2, catalyzed by aromatic L-amino acid decarboxylase using PLP. [Outside detail: the uploaded sources establish tryptophan → serotonin and BH4 dependence of tryptophan hydroxylase, but do not fully spell out this reaction sequence.]

What important cofactor is used by tryptophan hydroxylase?

Tetrahydrobiopterin (BH4). The slides identify BH4 as an essential cofactor for tryptophan hydroxylase.

Which amino acid is used to make phosphocreatine?

Creatine is synthesized from glycine, arginine, and methionine and then phosphorylated to phosphocreatine.

What is the metabolic role of phosphocreatine?

Phosphocreatine serves as a high-energy phosphate reserve that can rapidly regenerate ATP.

What is the pathway for creatine and phosphocreatine biosynthesis?

Arginine + glycine → guanidinoacetate + ornithine; guanidinoacetate + S-adenosylmethionine (SAM) → creatine + S-adenosylhomocysteine; creatine + ATP ⇌ phosphocreatine + ADP, catalyzed in the final step by creatine kinase.

Which three amino acids contribute to creatine biosynthesis?

Glycine, arginine, and methionine. Chapter 22 textbook(1)

Which compound is required for the synthesis of methionine?

N5-methyltetrahydrofolate (N5-methyl-THF) provides the methyl group required to convert homocysteine to methionine.

Why is N5-methyltetrahydrofolate required for methionine synthesis?

It supplies the one-carbon methyl group transferred to homocysteine by methionine synthase.

What is the folate-dependent pathway for methionine synthesis?

N5-methyl-THF + homocysteine → THF + methionine, catalyzed by methionine synthase with vitamin B12 participating in methyl transfer.

What vitamin is closely linked to folate during methionine synthesis?

Vitamin B12.

What are the bile pigments?

Biliverdin and bilirubin.

Where do bile pigments come from?

They arise from degradation of heme.

What is the pathway for bile-pigment production?

Heme + 3 O2 + 3 NADPH + 3 H+ → biliverdin + Fe2+ + CO + 3 NADP+ + 3 H2O via heme oxygenase; biliverdin + NADPH + H+ → bilirubin + NADP+ via biliverdin reductase.

What is bilirubin's relationship to heme metabolism?

Bilirubin is a bile pigment produced by reduction of biliverdin during heme degradation.