Podcast
Questions and Answers
Anabolic pathways require energy and use electron donors in reduction reactions.
Anabolic pathways require energy and use electron donors in reduction reactions.
True
Gluconeogenesis can occur without the use of glycerol, lactate, or amino acids as substrates.
Gluconeogenesis can occur without the use of glycerol, lactate, or amino acids as substrates.
False
NADPH is a high energy electron carrier used in anabolic processes.
NADPH is a high energy electron carrier used in anabolic processes.
True
The process of glycolysis can be simply reversed to produce glucose during gluconeogenesis.
The process of glycolysis can be simply reversed to produce glucose during gluconeogenesis.
Signup and view all the answers
All metabolic processes require energy.
All metabolic processes require energy.
Signup and view all the answers
Glycogen stores can last for up to 48 hours without replenishment.
Glycogen stores can last for up to 48 hours without replenishment.
Signup and view all the answers
NADPH is mainly used in energy yielding reactions.
NADPH is mainly used in energy yielding reactions.
Signup and view all the answers
NADH is primarily used for storing high energy phosphate bonds.
NADH is primarily used for storing high energy phosphate bonds.
Signup and view all the answers
The regulation of the PPP is mainly at the glucose-6-phosphate dehydrogenase reaction.
The regulation of the PPP is mainly at the glucose-6-phosphate dehydrogenase reaction.
Signup and view all the answers
Red blood cells, brain, and testes specifically need glucose as their preferred energy source.
Red blood cells, brain, and testes specifically need glucose as their preferred energy source.
Signup and view all the answers
NADH and NADPH can be acted on by the same enzymes.
NADH and NADPH can be acted on by the same enzymes.
Signup and view all the answers
Insulin decreases glucose-6-phosphate dehydrogenase gene expression.
Insulin decreases glucose-6-phosphate dehydrogenase gene expression.
Signup and view all the answers
Products from the cyclical phase can feed into the glycolytic pathway.
Products from the cyclical phase can feed into the glycolytic pathway.
Signup and view all the answers
Anaerobic glycolysis converts glucose to pyruvate by lactate dehydrogenase.
Anaerobic glycolysis converts glucose to pyruvate by lactate dehydrogenase.
Signup and view all the answers
Pyruvate carboxylase requires ATP for the conversion of pyruvate to oxaloacetate.
Pyruvate carboxylase requires ATP for the conversion of pyruvate to oxaloacetate.
Signup and view all the answers
Fructose-1,6-bisphosphatase is inhibited by AMP.
Fructose-1,6-bisphosphatase is inhibited by AMP.
Signup and view all the answers
Glucose-6-phosphatase is present in all body tissues.
Glucose-6-phosphatase is present in all body tissues.
Signup and view all the answers
The pentose phosphate pathway generates ATP during its reactions.
The pentose phosphate pathway generates ATP during its reactions.
Signup and view all the answers
Oxidative reactions in the pentose phosphate pathway produce NADPH.
Oxidative reactions in the pentose phosphate pathway produce NADPH.
Signup and view all the answers
Glucokinase and hexokinase catalyze the same reaction as fructose-1,6-bisphosphatase.
Glucokinase and hexokinase catalyze the same reaction as fructose-1,6-bisphosphatase.
Signup and view all the answers
The cyclical phase of the pentose phosphate pathway produces predominantly NADPH.
The cyclical phase of the pentose phosphate pathway produces predominantly NADPH.
Signup and view all the answers
Gluconeogenesis primarily occurs in the cytoplasm and requires malate for transport across the mitochondrial membrane.
Gluconeogenesis primarily occurs in the cytoplasm and requires malate for transport across the mitochondrial membrane.
Signup and view all the answers
The gluconeogenic step of converting pyruvate to oxaloacetate occurs in the endoplasmic reticulum.
The gluconeogenic step of converting pyruvate to oxaloacetate occurs in the endoplasmic reticulum.
Signup and view all the answers
NADPH is involved in biosynthetic processes such as lipid synthesis.
NADPH is involved in biosynthetic processes such as lipid synthesis.
Signup and view all the answers
The pentose phosphate pathway is a source of atoms for purine biosynthesis.
The pentose phosphate pathway is a source of atoms for purine biosynthesis.
Signup and view all the answers
Inosine 5’-monophosphate is not a common intermediate in nucleotide biosynthesis.
Inosine 5’-monophosphate is not a common intermediate in nucleotide biosynthesis.
Signup and view all the answers
The activator for PRPP synthetase is AMP.
The activator for PRPP synthetase is AMP.
Signup and view all the answers
Carbamoyl phosphate is synthesized using 2 ATP in pyrimidine biosynthesis.
Carbamoyl phosphate is synthesized using 2 ATP in pyrimidine biosynthesis.
Signup and view all the answers
Glutamine and CO2 are the source of atoms in the pyrimidine ring structure.
Glutamine and CO2 are the source of atoms in the pyrimidine ring structure.
Signup and view all the answers
UDP and UTP are intermediates in purine biosynthesis.
UDP and UTP are intermediates in purine biosynthesis.
Signup and view all the answers
Ribonucleotide reductase converts ribonucleotides into deoxyribonucleotides.
Ribonucleotide reductase converts ribonucleotides into deoxyribonucleotides.
Signup and view all the answers
Folic acid acts as an inhibitor in pyrimidine biosynthesis.
Folic acid acts as an inhibitor in pyrimidine biosynthesis.
Signup and view all the answers
NADPH helps combat oxidative stress by regenerating reduced glutathione (GSH).
NADPH helps combat oxidative stress by regenerating reduced glutathione (GSH).
Signup and view all the answers
Excessive breakdown of purine bases can lead to gout due to an excess of uric acid.
Excessive breakdown of purine bases can lead to gout due to an excess of uric acid.
Signup and view all the answers
Methotrexate and 5-FU are examples of drugs that promote dTMP synthesis.
Methotrexate and 5-FU are examples of drugs that promote dTMP synthesis.
Signup and view all the answers
Adenosine deaminase deficiency can lead to severe immunodeficiency.
Adenosine deaminase deficiency can lead to severe immunodeficiency.
Signup and view all the answers
All amino acids are classified as essential amino acids.
All amino acids are classified as essential amino acids.
Signup and view all the answers
Transamination is a process by which amine groups are moved between carbon backbones.
Transamination is a process by which amine groups are moved between carbon backbones.
Signup and view all the answers
Glutamine is synthesized from asparagine during amidation.
Glutamine is synthesized from asparagine during amidation.
Signup and view all the answers
Physiologically active amines include serotonin and dopamine.
Physiologically active amines include serotonin and dopamine.
Signup and view all the answers
Non-essential amino acids can only be synthesized from other amino acids.
Non-essential amino acids can only be synthesized from other amino acids.
Signup and view all the answers
Asparagine is synthesized from glutamate.
Asparagine is synthesized from glutamate.
Signup and view all the answers
Serine can be synthesized from 3-phosphoglycerate.
Serine can be synthesized from 3-phosphoglycerate.
Signup and view all the answers
NADPH is primarily involved in lipid synthesis and other biosynthetic reactions.
NADPH is primarily involved in lipid synthesis and other biosynthetic reactions.
Signup and view all the answers
Insulin reduces the expression of the glucose-6-phosphate dehydrogenase gene.
Insulin reduces the expression of the glucose-6-phosphate dehydrogenase gene.
Signup and view all the answers
The presence of a phosphate group differentiates NADPH from NADH and determines their specific enzyme interactions.
The presence of a phosphate group differentiates NADPH from NADH and determines their specific enzyme interactions.
Signup and view all the answers
The pentose phosphate pathway mainly functions to generate ATP for energy.
The pentose phosphate pathway mainly functions to generate ATP for energy.
Signup and view all the answers
NADH is utilized mainly in biosynthetic reactions.
NADH is utilized mainly in biosynthetic reactions.
Signup and view all the answers
Anabolic pathways primarily use high energy compounds like ATP and NADH for their reactions.
Anabolic pathways primarily use high energy compounds like ATP and NADH for their reactions.
Signup and view all the answers
Glucose must be formed from alternative precursors only when glycogen stores are fully replenished.
Glucose must be formed from alternative precursors only when glycogen stores are fully replenished.
Signup and view all the answers
The irreversibility of certain glycolysis steps does not require special routes for gluconeogenesis.
The irreversibility of certain glycolysis steps does not require special routes for gluconeogenesis.
Signup and view all the answers
Lactate, glycerol, and glucogenic amino acids can all serve as substrates for gluconeogenesis.
Lactate, glycerol, and glucogenic amino acids can all serve as substrates for gluconeogenesis.
Signup and view all the answers
The pentose phosphate pathway generates energy in the form of NADH during its reactions.
The pentose phosphate pathway generates energy in the form of NADH during its reactions.
Signup and view all the answers
NADPH primarily functions as a reducing agent in anabolic reactions.
NADPH primarily functions as a reducing agent in anabolic reactions.
Signup and view all the answers
Glycogen storage can last for more than 24 hours without being replenished.
Glycogen storage can last for more than 24 hours without being replenished.
Signup and view all the answers
NADH is essential for the production of ATP through oxidative phosphorylation.
NADH is essential for the production of ATP through oxidative phosphorylation.
Signup and view all the answers
Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate to pyruvate, which is a reversible step.
Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate to pyruvate, which is a reversible step.
Signup and view all the answers
Fructose-1,6-bisphosphatase is the gluconeogenic counterpart of phosphofructokinase.
Fructose-1,6-bisphosphatase is the gluconeogenic counterpart of phosphofructokinase.
Signup and view all the answers
The only tissues capable of releasing glucose to the bloodstream are the liver and brain.
The only tissues capable of releasing glucose to the bloodstream are the liver and brain.
Signup and view all the answers
The pentose phosphate pathway yields primarily ATP during its oxidative phase.
The pentose phosphate pathway yields primarily ATP during its oxidative phase.
Signup and view all the answers
Oxaloacetate can directly cross the mitochondrial membrane in its form produced by pyruvate carboxylase.
Oxaloacetate can directly cross the mitochondrial membrane in its form produced by pyruvate carboxylase.
Signup and view all the answers
The oxidative phase of the pentose phosphate pathway generates CO2 and 2 NADPH from one molecule of glucose-6-phosphate.
The oxidative phase of the pentose phosphate pathway generates CO2 and 2 NADPH from one molecule of glucose-6-phosphate.
Signup and view all the answers
Fructose-2,6-bisphosphate increases the rate of gluconeogenesis.
Fructose-2,6-bisphosphate increases the rate of gluconeogenesis.
Signup and view all the answers
In gluconeogenesis, glucose-6-phosphatase acts to release phosphate and is found in multiple tissues of the body.
In gluconeogenesis, glucose-6-phosphatase acts to release phosphate and is found in multiple tissues of the body.
Signup and view all the answers
Glycerol, lactate, and amino acids can all serve as substrates for gluconeogenesis.
Glycerol, lactate, and amino acids can all serve as substrates for gluconeogenesis.
Signup and view all the answers
NADH and NADPH play entirely the same roles in metabolic processes.
NADH and NADPH play entirely the same roles in metabolic processes.
Signup and view all the answers
NADPH is utilized exclusively in catabolic reactions.
NADPH is utilized exclusively in catabolic reactions.
Signup and view all the answers
The pentose phosphate pathway contributes to the synthesis of deoxyribonucleotides through its intermediates.
The pentose phosphate pathway contributes to the synthesis of deoxyribonucleotides through its intermediates.
Signup and view all the answers
ATP acts as an inhibitor for the enzyme PRPP synthetase.
ATP acts as an inhibitor for the enzyme PRPP synthetase.
Signup and view all the answers
Cofactors like tetrahydrofolate are crucial in the synthesis of pyrimidine nucleotides.
Cofactors like tetrahydrofolate are crucial in the synthesis of pyrimidine nucleotides.
Signup and view all the answers
Purine biosynthesis incorporates phosphorus from inorganic phosphate (Pi) as a major component.
Purine biosynthesis incorporates phosphorus from inorganic phosphate (Pi) as a major component.
Signup and view all the answers
UMP (uridine monophosphate) is a common intermediate in purine nucleotide degradation.
UMP (uridine monophosphate) is a common intermediate in purine nucleotide degradation.
Signup and view all the answers
Inosine 5’-monophosphate serves as a central intermediate in purine biosynthesis.
Inosine 5’-monophosphate serves as a central intermediate in purine biosynthesis.
Signup and view all the answers
GTP can be synthesized from IMP through a series of sequential reactions involving ADP.
GTP can be synthesized from IMP through a series of sequential reactions involving ADP.
Signup and view all the answers
Feedback inhibition in purine biosynthesis primarily involves PRPP as an inhibitor.
Feedback inhibition in purine biosynthesis primarily involves PRPP as an inhibitor.
Signup and view all the answers
NADPH is generated during the oxidative phase of the pentose phosphate pathway.
NADPH is generated during the oxidative phase of the pentose phosphate pathway.
Signup and view all the answers
Excessive breakdown of purine bases can lead to a condition called 'Gout' due to an excess of uric acid.
Excessive breakdown of purine bases can lead to a condition called 'Gout' due to an excess of uric acid.
Signup and view all the answers
Methotrexate and 5-FU act by promoting the synthesis of dTMP, aiding in cell division.
Methotrexate and 5-FU act by promoting the synthesis of dTMP, aiding in cell division.
Signup and view all the answers
Adenosine deaminase plays a critical role in the degradation pathway of AMP.
Adenosine deaminase plays a critical role in the degradation pathway of AMP.
Signup and view all the answers
Non-essential amino acids cannot be formed through transamination of ketoacids.
Non-essential amino acids cannot be formed through transamination of ketoacids.
Signup and view all the answers
Isolating purine biosynthesis involves common intermediates such as IMP.
Isolating purine biosynthesis involves common intermediates such as IMP.
Signup and view all the answers
Glutamine synthetase reaction is not important for transporting ammonia in a non-toxic form.
Glutamine synthetase reaction is not important for transporting ammonia in a non-toxic form.
Signup and view all the answers
Both purines and pyrimidines can originate from the same amino acids.
Both purines and pyrimidines can originate from the same amino acids.
Signup and view all the answers
Serotonin and epinephrine are examples of amino acid derivatives that serve as physiologically active amines.
Serotonin and epinephrine are examples of amino acid derivatives that serve as physiologically active amines.
Signup and view all the answers
Alanine is classified as a non-essential amino acid that can be synthesized from pyruvate via transamination.
Alanine is classified as a non-essential amino acid that can be synthesized from pyruvate via transamination.
Signup and view all the answers
All amino acids are classified as non-essential, meaning they cannot be synthesized by the body.
All amino acids are classified as non-essential, meaning they cannot be synthesized by the body.
Signup and view all the answers
Gluconeogenesis primarily occurs in the nucleus of the cell.
Gluconeogenesis primarily occurs in the nucleus of the cell.
Signup and view all the answers
Lactate and glycerol can be used as substrates for gluconeogenesis.
Lactate and glycerol can be used as substrates for gluconeogenesis.
Signup and view all the answers
ATP is generated from NADH during the process of gluconeogenesis.
ATP is generated from NADH during the process of gluconeogenesis.
Signup and view all the answers
The pentose phosphate pathway is essential for purine and pyrimidine biosynthesis.
The pentose phosphate pathway is essential for purine and pyrimidine biosynthesis.
Signup and view all the answers
The conversion of pyruvate to acetyl CoA is a reversible process in gluconeogenesis.
The conversion of pyruvate to acetyl CoA is a reversible process in gluconeogenesis.
Signup and view all the answers
NADPH is primarily utilized in biosynthetic reactions rather than energy yielding reactions.
NADPH is primarily utilized in biosynthetic reactions rather than energy yielding reactions.
Signup and view all the answers
Complex molecules in anabolic pathways are formed by linking simple precursors together.
Complex molecules in anabolic pathways are formed by linking simple precursors together.
Signup and view all the answers
NADPH primarily serves as an energy source for catabolic processes.
NADPH primarily serves as an energy source for catabolic processes.
Signup and view all the answers
Glucose-6-phosphate is an activator for the glucose-6-phosphate dehydrogenase reaction.
Glucose-6-phosphate is an activator for the glucose-6-phosphate dehydrogenase reaction.
Signup and view all the answers
The primary substrate for gluconeogenesis is fructose.
The primary substrate for gluconeogenesis is fructose.
Signup and view all the answers
Both NADPH and NADH serve as electron carriers in the same types of biochemical reactions.
Both NADPH and NADH serve as electron carriers in the same types of biochemical reactions.
Signup and view all the answers
Insulin decreases the expression of the glucose-6-phosphate dehydrogenase gene.
Insulin decreases the expression of the glucose-6-phosphate dehydrogenase gene.
Signup and view all the answers
The cyclical phase of the pentose phosphate pathway exclusively produces ribose 5-phosphate for DNA synthesis.
The cyclical phase of the pentose phosphate pathway exclusively produces ribose 5-phosphate for DNA synthesis.
Signup and view all the answers
Gluconeogenesis primarily occurs in the liver and kidneys, which are the only tissues that can release glucose to the bloodstream.
Gluconeogenesis primarily occurs in the liver and kidneys, which are the only tissues that can release glucose to the bloodstream.
Signup and view all the answers
The pentose phosphate pathway is a purely catabolic process that solely produces ATP.
The pentose phosphate pathway is a purely catabolic process that solely produces ATP.
Signup and view all the answers
Fructose-1,6-bisphosphatase catalyzes the irreversible conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
Fructose-1,6-bisphosphatase catalyzes the irreversible conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
Signup and view all the answers
NADPH is produced during both the oxidative phase and the cyclical phase of the pentose phosphate pathway.
NADPH is produced during both the oxidative phase and the cyclical phase of the pentose phosphate pathway.
Signup and view all the answers
PEP carboxykinase catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in both the mitochondrion and cytosol.
PEP carboxykinase catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in both the mitochondrion and cytosol.
Signup and view all the answers
The dephosphorylation of glucose-6-phosphate is carried out only by glucose-6-phosphatase present in skeletal muscle.
The dephosphorylation of glucose-6-phosphate is carried out only by glucose-6-phosphatase present in skeletal muscle.
Signup and view all the answers
During the oxidative phase of the pentose phosphate pathway, one molecule of glucose-6-phosphate is converted to two molecules of NADPH and one molecule of ribulose-5-phosphate.
During the oxidative phase of the pentose phosphate pathway, one molecule of glucose-6-phosphate is converted to two molecules of NADPH and one molecule of ribulose-5-phosphate.
Signup and view all the answers
Lactate dehydrogenase converts pyruvate to lactate, not to oxaloacetate.
Lactate dehydrogenase converts pyruvate to lactate, not to oxaloacetate.
Signup and view all the answers
Amino acids can enter the TCA cycle directly as TCA intermediates without any conversion.
Amino acids can enter the TCA cycle directly as TCA intermediates without any conversion.
Signup and view all the answers
Excessive breakdown of pyrimidine bases can lead to a condition known as gout.
Excessive breakdown of pyrimidine bases can lead to a condition known as gout.
Signup and view all the answers
Glucagon increases the rate of gluconeogenesis by decreasing levels of fructose-2,6-bisphosphate.
Glucagon increases the rate of gluconeogenesis by decreasing levels of fructose-2,6-bisphosphate.
Signup and view all the answers
All amino acids are classified as non-essential amino acids.
All amino acids are classified as non-essential amino acids.
Signup and view all the answers
The enzyme adenosine deaminase plays a crucial role in the degradation pathway for AMP.
The enzyme adenosine deaminase plays a crucial role in the degradation pathway for AMP.
Signup and view all the answers
Methotrexate acts by promoting the synthesis of dTMP in cancer cells.
Methotrexate acts by promoting the synthesis of dTMP in cancer cells.
Signup and view all the answers
Transamination reactions can generate non-essential amino acids from ketoacids.
Transamination reactions can generate non-essential amino acids from ketoacids.
Signup and view all the answers
Glutamine is synthesized from glutamate through a reaction that requires AMP.
Glutamine is synthesized from glutamate through a reaction that requires AMP.
Signup and view all the answers
Physiologically active amines are solely derived from non-essential amino acids.
Physiologically active amines are solely derived from non-essential amino acids.
Signup and view all the answers
The presence of uric acid in excess can lead to inflammation in joints and kidneys.
The presence of uric acid in excess can lead to inflammation in joints and kidneys.
Signup and view all the answers
Asparagine can be synthesized from aspartate through a reaction catalyzed by asparagine synthetase.
Asparagine can be synthesized from aspartate through a reaction catalyzed by asparagine synthetase.
Signup and view all the answers
The carbon skeleton of amino acids is derived from ribose in the pentose phosphate pathway.
The carbon skeleton of amino acids is derived from ribose in the pentose phosphate pathway.
Signup and view all the answers
PRPP is a crucial activator in the synthesis of purine nucleotides.
PRPP is a crucial activator in the synthesis of purine nucleotides.
Signup and view all the answers
The pentose phosphate pathway produces UTP as a primary product.
The pentose phosphate pathway produces UTP as a primary product.
Signup and view all the answers
Glutamine and CO2 supply the carbon atoms for the pyrimidine ring structure.
Glutamine and CO2 supply the carbon atoms for the pyrimidine ring structure.
Signup and view all the answers
AMP serves as an activator for ribonucleotide reductase.
AMP serves as an activator for ribonucleotide reductase.
Signup and view all the answers
Ribonucleotide reductase operates specifically converting deoxyribonucleotides into ribonucleotides.
Ribonucleotide reductase operates specifically converting deoxyribonucleotides into ribonucleotides.
Signup and view all the answers
Thymidylate synthase requires tetrahydrofolate as a cofactor.
Thymidylate synthase requires tetrahydrofolate as a cofactor.
Signup and view all the answers
The feedback inhibition in nucleotide biosynthesis is primarily due to the accumulation of ribose-5-phosphate.
The feedback inhibition in nucleotide biosynthesis is primarily due to the accumulation of ribose-5-phosphate.
Signup and view all the answers
Dihydropyrimidine dehydrogenase is responsible for the degradation of pyrimidines into uric acid.
Dihydropyrimidine dehydrogenase is responsible for the degradation of pyrimidines into uric acid.
Signup and view all the answers
NADPH plays a key role in biosynthetic pathways such as nucleotide synthesis.
NADPH plays a key role in biosynthetic pathways such as nucleotide synthesis.
Signup and view all the answers
The synthesis of OMP occurs after the addition of ribose-5-phosphate to the pyrimidine ring.
The synthesis of OMP occurs after the addition of ribose-5-phosphate to the pyrimidine ring.
Signup and view all the answers
Study Notes
Anabolic Pathways
- Anabolic pathways require energy, use electron donors for reduction reactions, and build complex molecules from simple precursors.
- Energy sources include ATP, NADH, and NADPH.
Gluconeogenesis
- Occurs when glycogen stores are depleted and glucose must be made from other precursors.
- Key precursors include lactate, glycerol, and glucogenic amino acids.
- Bypasses irreversible steps of glycolysis.
- Occurs in liver and kidney.
Steps of Gluconeogenesis
- Carboxylation of pyruvate: Pyruvate is converted to oxaloacetate by pyruvate carboxylase. This occurs in the mitochondria.
- Dephosphorylation of fructose-1,6-bisphosphate: Fructose-1,6-bisphosphate is converted to fructose-6-phosphate by fructose-1,6-bisphosphatase. This step is regulated by AMP and fructose-2,6-bisphosphate.
- Dephosphorylation of glucose-6-phosphate: Glucose-6-phosphate is converted to glucose by glucose-6-phosphatase. This occurs in the endoplasmic reticulum.
Pentose Phosphate Pathway (PPP)
- Occurs in the cytoplasm.
- Generates NADPH and 5-carbon sugars for biosynthetic processes.
- Has two phases: oxidative and cyclical.
- Oxidative phase produces NADPH and ribulose-5-P.
- Cyclical phase interconverts 3, 4, 5, 6, and 7-carbon sugars.
Regulation of the PPP
- Regulated by glucose-6-phosphate dehydrogenase.
- NADPH is a competitive inhibitor of the enzyme.
- Insulin increases G6PD gene expression, increasing pathway activity in a well-fed state.
NADPH vs NADH
- NADPH is used in biosynthetic reactions.
- NADH is used in energy-yielding reactions (oxidative phosphorylation).
- They are not metabolically interchangeable.
Uses of NADPH
- Biosynthetic reactions (lipid synthesis).
- Protective mechanisms (combat oxidative stress, regenerate reduced glutathione).
Nucleotide Biosynthesis
- Purine biosynthesis: A, G; common intermediate is IMP.
- Pyrimidine biosynthesis: C, T, U; common intermediate is UMP.
Clinical Aspects of Nucleotide Metabolism
- Anti-cancer drugs often target dTMP synthesis to inhibit cell division.
- Gout results from excess uric acid buildup due to purine breakdown.
- Adenosine deaminase deficiency causes severe immunodeficiency.
Amino Acid Biosynthesis
- Essential amino acids cannot be synthesized by the body.
- Non-essential amino acids can be synthesized.
Transamination
- Aminotransferases move amino groups between different carbon backbones.
- Reversible reactions allow for generation of non-essential amino acids.
Amidation
- Glutamine and asparagine synthesis.
- Glutamine synthetase also transports ammonia in a non-toxic form.
Synthesis of Non-Essential Amino Acids
- Many non-essential amino acids are synthesized from metabolic intermediates like pyruvate, oxaloacetate, and α-ketoglutarate.
Biosynthesis of Physiologically Active Amines
- GABA, histamine, serotonin, epinephrine, norepinephrine, and dopamine are all amino acid derivatives.
Anabolic Pathways
- Anabolic pathways require energy for the formation of complex molecules from simple precursors
- Electron donors are used in reduction reactions
- ATP, NADH, and NADPH are essential sources of energy for anabolism
- ATP provides energy through high-energy phosphate bonds and reducing power
- NADH and NADPH are high-energy electron carriers, providing reducing power for biosynthesis
Gluconeogenesis
- Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors
- Most tissues rely on glucose as their primary energy source
- Gluconeogenesis is crucial when glycogen stores are depleted, which occurs after 10-18 hours
- The primary precursors for gluconeogenesis include lactate, glycerol, and glucogenic amino acids
- Gluconeogenesis cannot simply reverse glycolysis due to irreversible steps
- Special pathways bypass irreversible steps, such as the conversion of pyruvate to acetyl CoA
- Substrates for gluconeogenesis:
- Glycerol from triglyceride backbones
- Lactate from anaerobic glycolysis
- Amino acids converted to TCA intermediates and oxaloacetate
Carboxylation of Pyruvate
- Pyruvate carboxylase converts pyruvate to oxaloacetate in mitochondria
- PEP carboxykinase converts oxaloacetate to phosphoenolpyruvate (PEP) in mitochondria and cytosol
- Oxaloacetate can't cross the mitochondrial membrane, so it is converted to malate or aspartate for transport
Dephosphorylation of Fructose-1,6-bisphosphate
- Fructose-1,6-bisphosphatase reverses the glycolytic step catalyzed by phosphofructokinase
- This step is regulated by AMP and fructose 2,6-bisphosphate, which is decreased by glucagon
- Glucagon stimulates gluconeogenesis by decreasing fructose 2,6-bisphosphate levels
Dephosphorylation of Glucose-6-phosphate
- Glucose-6-phosphatase releases phosphate from glucose-6-phosphate
- The reaction occurs in the endoplasmic reticulum and requires a glucose-6-phosphate translocase
- Glucose-6-phosphatase is present only in the liver and kidneys, which are the only gluconeogenic tissues.
Gluconeogenesis and Glycolysis Compared
- Gluconeogenesis bypasses irreversible steps in glycolysis
- Gluconeogenesis requires energy (2 ATP and 2 GTP)
Pentose Phosphate Pathway (PPP)
- PPP is an anabolic pathway producing NADPH and 5-carbon sugars for biosynthesis
- It is more anabolic than catabolic and occurs in the cytoplasm.
- PPP produces a significant portion of the body's NADPH
- The pathway consists of two phases:
- Oxidative phase: produces NADPH
- Cyclical phase: produces 5-carbon sugars
PPP and Glycolysis Interconnection
- Glucose-6-phosphate (G6P) from glycolysis enters the PPP
- PPP produces NADPH and ribose-5-phosphate for biosynthesis
- Some intermediates re-enter glycolysis
PPP Regulation
- The rate and direction of the PPP are influenced by the supply of G6P and the demand for intermediates
- The pathway is mainly regulated at the glucose-6-phosphate dehydrogenase step.
- NADPH acts as a competitive inhibitor of glucose-6-phosphate dehydrogenase.
- Insulin increases G6PD expression to boost pathway activity during a well-fed state.
NADPH vs. NADH
- NADPH – mainly for biosynthesis
- NADH – mainly for energy production in oxidative phosphorylation.
- NADPH and NADH generally have distinct enzymatic roles and aren't metabolically interchangeable.
NADPH Uses
- Biosynthesis:
- Cholesterol
- Steroid hormones
- Sphingomyelin
- Fatty acids
- Certain phospholipids
- Protection: combats oxidative stress by regenerating reduced glutathione (GSH)
Nucleotide Biosynthesis
- Key elements for purine biosynthesis include:
- Pentose phosphate pathway provides ribose-5-phosphate.
- Amino acids provide nitrogenous bases.
- Key elements for pyrimidine biosynthesis include:
- Glutamine and carbon dioxide are essential for the synthesis of carbamoyl phosphate
- PRPP donates ribose-5-phosphate
- Common intermediates:
- Inosine 5’-monophosphate (IMP) for purine synthesis
- Orotidine 5’-monophosphate (OMP) for pyrimidine synthesis
Nucleotide Degradation
- Pyrimidine bases are broken down to simple carbon skeletons
- Purine bases are either salvaged for reuse or degraded:
- Purine bases are converted to xanthine and then to uric acid, which is excreted.
Clinical Aspects of Nucleotide Metabolism
- Many anti-cancer drugs (chemotherapy) act by inhibiting dTMP synthesis, preventing DNA replication
- Excessive breakdown of purine bases can lead to gout (uric acid crystals cause inflammation in joints and kidneys)
- Adenosine deaminase deficiency: enzyme deficiency leading to severe immunodeficiency
Amino Acid Biosynthesis
- Essential amino acids – cannot be synthesized by the body, must be obtained from the diet
- Non-essential amino acids – can be synthesized from metabolic intermediates
- Amino acids are important for building proteins and other biomolecules
Amino Acid Structure
- Amino
- Carboxyl
- Side chain (R group)
Transamination
- Aminotransferases move amide groups between different carbon backbones.
- Transamination reactions are reversible.
- Non-essential amino acids can be generated through the transamination of ketoacids
Amidation
- Glutamine synthetase converts glutamate to glutamine.
- Asparagine synthetase converts aspartate to asparagine.
- Glutamine synthetase also plays a critical role in transporting ammonia in a non-toxic form
Synthesis of Non-Essential Amino Acids
- Alanine, aspartate, glutamate are synthesized through transaminase reactions
- Glutamine and asparagine are synthesized by dedicated enzymes (glutamine synthase, asparagine synthase)
- Proline is synthesized from glutamate via cyclic reactions
- Serine is synthesized from 3-phosphoglycerate
- Glycine is synthesized from serine
Biosynthesis of Physiologically Active Amines
- Physiologically active amines are derived from amino acids
- GABA, histamine, serotonin, dopamine, epinephrine, and norepinephrine are examples of physiologically active amines.
Anabolic Pathways
- Anabolic pathways require energy and use electron donors for reduction reactions.
- Anabolic pathways build complex molecules from simple precursors.
- All anabolic processes require energy.
Energy Sources for Anabolism
- ATP provides high energy phosphate bonds.
- NADH and NADPH provide high energy electrons, referred to as reducing power.
- NADH contributes to oxidative phosphorylation, which generates ATP.
Gluconeogenesis
- Some tissues depend on glucose as their primary energy source, including red blood cells, brain, testes, and the lens of the eye.
- Glycogen stores provide glucose for 10-18 hours.
- When glycogen stores are depleted, glucose is produced from other precursors: mainly lactate, glycerol, and glucogenic amino acids.
- Some glycolysis steps are irreversible, which requires specialized pathways for gluconeogenesis to bypass these steps.
Gluconeogenesis: Substrates
- Glycerol: Glycerol is obtained from the triglyceride backbone, converted to glycerol phosphate, and eventually becomes glyceraldehyde-3-phosphate (a glycolytic intermediate).
- Lactate: Lactate is produced from anaerobic glycolysis and converted to pyruvate by lactate dehydrogenase.
- Amino Acids: Amino acids are converted to TCA intermediates and oxaloacetate, entering the TCA cycle. Some amino acids are converted to glycolytic intermediates.
Gluconeogenesis: Steps
-
Carboxylation of Pyruvate:
- Glycolytic Step: Pyruvate kinase irreversibly converts phosphoenolpyruvate to pyruvate.
-
Gluconeogenic Steps:
- Pyruvate carboxylase converts pyruvate to oxaloacetate, requiring ATP and occurring in the mitochondria.
- PEP carboxykinase converts oxaloacetate to PEP, using GTP and occurring in both the mitochondria and cytosol.
- Mitochondrial oxaloacetate cannot cross the mitochondrial membrane directly but is converted to malate or aspartate for transport, then reconverted in the cytosol.
-
Dephosphorylation of Fructose-1,6-bisphosphate:
- Glycolytic Step: Phosphofructokinase irreversibly converts fructose-6-phosphate to fructose-1,6-bisphosphate.
- Gluconeogenic Step: Fructose 1,6 bisphosphatase reverses the reaction.
- Control: Inhibited by AMP and fructose 2,6-bisphosphate. Glucagon decreases fructose 2,6-bisphosphate levels, increasing gluconeogenesis.
-
Dephosphorylation of Glucose-6-phosphate:
- Glycolytic Step: Hexokinase irreversibly converts glucose to glucose-6-phosphate.
- Gluconeogenic Steps: Glucose-6-phosphatase removes phosphate from glucose-6-phosphate. This requires glucose-6-phosphate translocase to transport glucose-6-phosphate into the endoplasmic reticulum.
- Tissue Specificity: Glucose-6-phosphatase is present only in the liver and kidneys, making these the only tissues capable of gluconeogenesis and releasing glucose into the bloodstream.
Gluconeogenesis and Glycolysis Contrast
- Gluconeogenesis has different enzymes than glycolysis for the irreversible steps.
- Gluconeogenesis requires energy (2 ATP and 2 GTP), while glycolysis generates energy (2 ATP).
Pentose Phosphate Pathway (PPP)
- Also known as the hexose monophosphate shunt/pathway or phosphogluconate pathway.
- Generates NADPH and 5-carbon sugars for biosynthetic processes.
- More anabolic than catabolic.
- Occurs in the cytoplasm.
- Produces a major proportion of the body's NADPH.
-
Two Phases:
- Oxidative phase: Produces NADPH (the main function of this pathway).
- Cyclical phase: Generates 5-carbon sugars.
Pentose Phosphate Pathway & Glycolysis Relationship
- Glucose-6-phosphate (G6P) is the starting point and can be funneled into the PPP or continue through glycolysis.
Pentose Phosphate Pathway: Oxidative Phase
- Two irreversible reactions convert glucose-6-P to ribulose-5-P, CO2, and 2 NADPH.
-
Catalyzed by:
- Glucose 6-phosphate dehydrogenase (G6PD)
- 6-phosphogluconolactone hydrolase
Pentose Phosphate Pathway: Cyclical Phase
- Reversible non-oxidative reactions interconvert 3, 4, 5, 6, and 7-carbon sugars.
-
Key Intermediates:
- Ribose 5-P for DNA and RNA synthesis
- Intermediates can feed into the glycolytic pathway.
Pentose Phosphate Pathway Regulation
- The rate and direction of reversible reactions are determined by the supply of glucose-6-P and the demand for intermediates.
-
Main Regulation Point: Glucose-6-P dehydrogenase reaction:
- NADPH is a competitive inhibitor.
- Insulin increases G6PD gene expression, increasing pathway activity in a well-fed state.
NADPH vs NADH
- NADPH: Nicotinamide adenine dinucleotide phosphate. Primarily used in biosynthetic reactions.
- NADH: Nicotinamide adenine dinucleotide. Primarily used in energy-yielding reactions (oxidative phosphorylation).
- They are not metabolically interchangeable due to the phosphate group in NADPH.
NADPH Uses
- Biosynthesis: Lipid synthesis (including cholesterol, steroid hormones, sphingomyelin, fatty acids, and certain phospholipids).
- Protective: Combats oxidative stress by regenerating reduced glutathione (GSH).
Nucleotide Biosynthesis & Degradation
- Purine biosynthesis (A, G)
- Pyrimidine biosynthesis (C, T, U)
- Nucleotide degradation
Purine Biosynthesis
- Source of atoms in the purine ring structure: Pentose phosphate pathway.
-
Key Steps:
- Precursor activation: PRPP synthetase converts ribose-5-phosphate to PRPP, using ATP. PRPP is a key intermediate in the pathway.
- PRPP amidotransferase converts PRPP to 5'-phosphoribosylamine.
- Common intermediate: IMP (inosine 5'-monophosphate).
- End products: AMP (adenine) and GMP (guanine).
Pyrimidine Biosynthesis
-
Key Steps:
- Carbamoyl phosphate synthetase II: Synthesizes carbamoyl phosphate.
- Orotidine 5'-monophosphate (OMP): A key intermediate in the pathway.
- Common Intermediate: UMP (uridine monophosphate).
- End products: CMP (cytosine), TMP (thymine), and UTP (uracil).
Nucleotide Degradation
- Pyrimidines: Bases are broken down to simple carbon skeletons (β-Alanine or β-Aminoisobutyrate) and degraded further.
-
Purines: Bases are either reused (salvaged) or degraded:
- Pathway: Purine bases --> Xanthine --> Uric acid --> Excretion
Clinical Aspects of Nucleotide Metabolism
- Chemotherapy: Many drugs act by inhibiting dTMP synthesis, preventing DNA replication and cell division (e.g., methotrexate and 5-FU).
- Gout: Excessive breakdown of purine bases leads to uric acid accumulation, which can crystallize in the joints and kidneys, causing inflammation and pain.
- Adenosine Deaminase Deficiency: Genetic deficiency in the enzyme adenosine deaminase disrupts AMP degradation, leading to severe immunodeficiency.
Key Points about Nucleotide Pathways
- Source of Atoms: Amino acids for the purine and pyrimidine rings, ribose from the pentose phosphate pathway.
- Common Intermediates: IMP for G, C, and OMP for C, T, U.
- Regulation: Feedback inhibition and precursor activation.
- Clinical Relevance: Gout (purines), chemotherapy (thymidylate synthase and dihydrofolate reductase).
Biosynthesis of Amino Acids
- Essential Amino Acids: Must be obtained from the diet, cannot be synthesized by the body (arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine).
- Non-Essential Amino Acids: Can be synthesized by the body (alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine).
Amino Acid Structure
- A carbon skeleton attached to an amino group (NH3+).
Transamination
- Function: Moves amide groups between different carbon backbones.
- Reversible: Aminotransferases (enzymes) can catalyze the reaction in both directions.
- Non-Essential Amino Acid Synthesis: Transamination can generate non-essential amino acids from ketoacids.
Amidation
- Function: Adds amide groups to molecules.
-
Key Reactions:
- Glutamine synthetase: Glutamate + ATP + NH3 --> Glutamine + ADP + phosphate. Glutamine synthetase is also important for transporting ammonia in a non-toxic form.
- Asparagine synthetase: Aspartate + ATP + Glutamine --> Asparagine + AMP + PPi + Glutamate.
Synthesis of Non-Essential Amino Acids from Metabolic Intermediates
- Starting Points: Glucose, 3-phosphoglycerate (3-PG), α-ketoglutarate.
-
Reactions:
- Alanine: Pyruvate --> Alanine via transaminase.
- Aspartate: Oxaloacetate --> Aspartate via transaminase.
- Glutamate: α-ketoglutarate --> Glutamate via transaminase or glutamate dehydrogenase (GDH).
- Asparagine: Aspartate --> Asparagine via asparagine synthase.
- Glutamine: Glutamate --> Glutamine via glutamine synthase.
- Proline: Glutamate --> Proline via a series of reactions involving cyclisation.
- Serine: 3-phosphoglycerate --> Serine via a series of reactions.
- Glycine: Serine --> Glycine via serine hydroxymethyl transferase.
Biosynthesis of Physiologically Active Amines
- Active amines derived from amino acids: GABA, histamine, serotonin, epinephrine, norepinephrine, and dopamine.
- Importance: Neurotransmitters, hormones, and other regulatory molecules.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Explore the critical processes of anabolic pathways and gluconeogenesis, including their energy requirements and key steps. This quiz covers the conversion processes in the liver and kidney, focusing on the transformation of pyruvate and other precursors into glucose. Test your understanding of metabolic pathways and their regulation.
