Regulation of Metabolism Flashcards
Which pathway(s) can be involved in increasing blood glucose concentrations? (There may be more than one answer)
a) Glycolysis
b) Glycogenesis
c) Gluconeogenesis
d) Glycogenolysis
c & d
What is the pathway responsible for converting glucose into pyruvate called?
Glycolysis
What is the pathway responsible for converting pyruvate into glucose called?
Gluconeogenesis
What is the pathway responsible for converting glucose into glycogen called?
Glycogenesis
What is the pathway responsible for converting glycogen into glucose called?
Glycogenolysis
How many steps does glycolysis consist of?
10 steps
What does the preparatory phase of glycolysis involve?
The phosphorylation of a molecule of glucose and it’s conversion into two molecules of Glyceraldehyde-3-phosphate
How many molecules of ATP are used in the preparatory phase of glycolysis?
2
What does the payoff phase of glycolysis involve?
The conversion of both molecules of glyceraldehyde-3-phosphate into two molecule of pyruvate
How many ATP and NADH molecules are released in the payoff phase of glycolysis?
4 ATP
2 NADH
What is the overall reaction of glycolysis?
Glucose + 2NAD+ + 2ADP + 2Pi -> 2Pyruvate + 2NADH + 2H+ + 2ATP
Under what conditions is the pathway of glycolysis active?
ATP is low
ADP is high
NADH to NAD+ ratio is low
AMP is relatively high
Where does gluconeogenesis primarily occur?
Liver cells
How many reactions in the glycolytic pathway are reversible?
7
What is the overall reaction of gluconeogenesis?
2Pyruvate + 4ATP + 2GTP + 2NADH + 2H+ + 4H2O -> Glucose + 4ADP + 2GDP + 6Pi + 2NAD+
Why are some of the enzymatic reactions in the pathways of glycolysis and gluconeogenesis irreversible under normal physiological conditions?
They have very high ΔG values
Under what conditions would gluconeogenesis be active in the liver?
When glycogen stores start to deplete such as during an overnight fast
What is the 1st futile cycle?
The first step of glycolysis and the last step of gluconeogenesis where glucose is converted into glucose-6-phosphate (and vice versa)
Which enzyme is required to convert glucose into glucose-6-phosphate in glycolysis?
Hexokinase
What enzyme is required to convert glucose-6-phosphate into glucose in gluconeogenesis?
Glucose-6-phosphatase
Where is hexokinase found?
In all cells which have the glycolytic pathway
Where is glucose-6-phosphatase found?
Hepatocytes (liver cells)
What type of hexokinase is found in liver cells?
Hexokinase IV
What type of hexokinase is found in muscle cells?
Hexokinase I and II
Which has a higher affinity (lower Km) for glucose: muscle hexokinase or liver hexokinase?
Muscle hexokinases
What is the other name for glucokinase?
Hexokinase IV
Why is it important for the hexokinase in the liver to have a high Km?
This hexokinase requires a high concentration of glucose in order for the reaction to take place. This means that glucose isn’t used up in the liver when the blood-glucose concentration is low
What happens to glucose in the liver when the blood-glucose levels are low?
The glucose produced in the liver by gluconeogenesis will not undergo glycolysis because the hexokinase has a high Km, therefore it will leave the liver cells and increase the blood-glucose concentration
Which isozymes of hexokinase is not inhibited by G-6-P?
Hexokinase IV
What is the 2nd futile cycle?
The conversion of Fructose-6-phosphate into fructose-1,6-bisphosphate and the reverse reaction in gluconeogenesis
What enzyme is responsible for converting fructose-6-phosphate into fructose-1,6-bisphosphate in glycolysis?
Phosphofructokinase-1 (PFK-1)
What enzyme is responsible for converting fructose-1,6-bisphosphate into fructose-6-phosphate in gluconeogenesis?
Fructose 1,6, bisphosphatase-1 (FBP-1)
True or False:
PFK-1 has both substrate-binding and regulator-binding sites
True
Is ATP an activator or inhibitor of PFK-1?
Inhibitor
How does citrate effect PFK-1?
Citrate is a key intermediate in aerobic metabolism and an allosteric regulator of PFK-1. High concentrations of citrate increases the inhibitory action of ATP and signals the cell that it is meeting current energy needs
Is ATP an activator or inhibitor of fructose 1,6 bisphosphatase?
Inhibitor
What hormone is secreted when blood-glucose levels drop?
Glucagon
What effects does glucagon have?
- Activates gluconeogenesis in the liver
- Causes the breakdown of glycogen
Both cause an increase in blood-glucose levels
What hormone is released when blood-glucose levels are high?
Insulin
How does Fructose-2,6-bisphosphate effect the enzymes in the 2nd futile cycle?
Activates PFK-1 and inhibits FBPase-1
Which enzyme catalyses the conversion of fructose-6-phosphate into fructose-2,6-bisphosphate?
PFK-2
Which enzyme catalyses the conversion of fructose-2,6-bisphosphate into fructose-6-phosphate?
FBPase-2
What controls the activity of PFK-2 and FBPase-2?
Insulin activates PFK-2 and glucagon activates FBPase-2
What is the 3rd futile cycle?
The conversion of 2-phosphoenol-pyruvate into pyruvate in glycolysis and the reverse reaction in gluconeogenesis
What is the enzyme that catalyses the conversion of 2-phosphoenol-pyruvate into pyruvate?
Pyruvate kinase
How many reactions are required to convert pyruvate into 2-phosphoenol-pyruvate?
2
What is the intermediate of the conversion of pyruvate into 2-phosphoenol-pyruvate?
Oxaloacetate
What enzyme is required to convert pyruvate into oxaloacetate?
Pyruvate carboxylase
What enzyme is required to convert oxaloacetate into 2-phosphoenol-pyruvate?
Phosphenol pyruvate carboxylase
How many isozymes of pyruvate kinase are there?
3
What are inhibitors of pyruvate kinase?
ATP
Acetyl CoA
Long chain fatty acids
What activates pyruvate kinase?
Fructose-1,6-bisphosphate
How does glucagon effect pyruvate kinase?
Glucagon increases the levels of cyclic AMP (cAMP) which activates the cAMP-dependent protein kinase. This phosphorylates and inactivates the liver isoforms of pyruvate kinase and causes the liver cells to consumer less glucose
How does epinephrine effect pyruvate kinase?
Epinephrin causes an increase of cAMP in the muscles which activates glycolysis
What are the two ways pyrimidines are synthesised?
De novo synthesis
Salvage pathways
What is de novo synthesis?
Synthesis of pyrimidines from small precursors (amino acids, PRPP, CO2, formate) where the free bases are not intermediates. The pyrimidine ring is synthesised as orotate, attached to ribose then converted
What is the salvage pathways?
synthesis of pyrimidines from nucleosides or bases from the diet or nucleic acid breakdown
What is the enzyme responsible for converting ribonucleotides into deoxyribonucleotides?
Ribonucleotude reductase
How are purines synthesised?
De novo synthesis
Salvage pathway
What are the characteristics of the de novo purine synthesis?
- Free bases are not intermediates
- The purine ring structure is built onto phosphoribosyl pyrophosphate (PRPP) in 11 steps to give the precursor purine inosinate (IMP)
- The atoms of the purine ring are contributed by a number of compounds, including amino acids (aspartic acid, glycine and glutamine), CO2 and folate derivatives
- Inosinate (IMP) is the first intermediate to have a complete purine ring
- IMP is then converted to AMP and GMP
What is produced when purines are degraded?
Uric acid
Which molecules act has inhibitors in the regulation of purine synthesis?
IMP
AMP
GMP
Which enzyme allows cell to reuse degraded guanine?
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Which enzyme allows cells to reuse degraded adenine?
Adenine phosphoribosyltransferase
What conditions are caused by abnormal purine metabolism?
Gout, SCID and Lesch-Nyhan Syndrome
What is the defect and symptoms of Gout?
Defect: Enzymes of purine breakdown
Symptoms: High uric acid and arthritus
What is the defect and symptoms of SCID?
Defect: ADA deficiency
Symptoms: High dATP, loss of T and B cells and immune deficiency
What is the defect and symptoms of Lesch-Nyhan Syndrome?
Defect: HGPRT deficiency
Symptoms: High PRPP and Uric Acid, Gout, Brain Damage and Self-mutilation
What are the largest family of cell surface receptors?
G-protein coupled receptors (GPCRs)
How many transmembrane segments does a GPCR have?
7
What signalling molcules are recognised by GPCRs?
Hormones, neurotransmitters and peptides
What happens when a GPCR is activated?
Binding of a ligand to its specific receptor induces a conformational change in a GPCR triggering the activation of its associated G protein
What is the structure of a G-protein?
This G protein is a trimeric, GTP-binding protein consisting of an α, β and γ subunits. The α and γ subunit each have lipid tails that allow them to remain anchored to the cell membrane.
What is the state of the α subunit in its inactive form?
In its inactive form, the α subunit of the trimeric G protein is bound to guanosine diphosphate (GDP)
What happens to the subunits when the G-protein is activated?
When activated, GDP is released and the α subunit quickly binds a molecule of guanosine diphosphate (GTP). This subsequently triggers the release of the α subunit from both the receptor and the β/γ subunits which are also now active yet remain bound to each other. The active subunits then act on target proteins that stimulate second messengers
What is Chronic Myeloid Leukaemia (CML)?
Overproduction of white blood cells in the bone marrow resulting in an ‘overflow’ of immature white blood cells into the blood stream.
What causes CML?
Overactive intracellular cellular signalling pathways that lead to cell proliferation, growth and survival.
What causes the overactivation of cell signalling pathways in CML?
Expression of an oncogenic tyrosine kinase that is capable of phosphorylating, and hence activating, subsequent kinases in cell proliferation pathways including the Ras/MAPK pathway, PI3K/Akt pathway and the JAK/STAT pathway
What is Gleevec and what can it be used to treat?
Gleevec is a small molecule enzyme inhibitor given to patients with CML
How does Gleevec work?
Gleevec is capable of binding to BCR-ABL at the ATP binding site, preventing its phosphorylation. This in turn inhibits it from activating subsequent kinases in cell proliferation pathways
What are monoclonal antibodies?
A type of antibody used to treat some cancers that can inhibit cell surface receptors. These antibodies bind competitively with a receptors ligand binding site, preventing its activation via its ligand
What factors regulate enzyme activity?
Amount of enzyme Location of enzyme Amount of substrate Allosteric effectors Enzyme phosphorylation Regulatory proteins
What does the sequence at the N-terminus of a protein determine?
Stability of the protein; it indicates when the protein needs to be degraded
True or False:
Inducible enzymes are constantly required in the body
False
Constitutive enzymes are required constantly. Inducuble/repressible enzymes aren’t always needed
What enzymes are induced by insulin?
Hexokinase/glucokinase
PFK-1
Where is Glucose-6-phosphatase found?
Gluconeogenic tissues (liver and kidney)
True or False:
Isoenzymes are the result of different expression of a single gene
False
They are the product of different genes
Which isoenzyme has a higher affinity for glucose: Glucokinase or hexokinase?
Hexokinase (lower Km than glucokinase_
What state is PFK-2 in when it is phosphorylated?
Inactive
What state is FBPase-2 in when it is phosphorylated?
Active
When blood-glucose levels are low what hormone is secreted?
Glucagon
What feature of cells is stimulated by insulin?
GLUT 1-5 transporters
They facilitate the taking up of glucose by the cell
What regulates glucose hoeostasis?
Allosteric regulation of glycogen synthase and glycogen phosphorylase
Hormonal regulation
What do phosphatases do?
Remove phosphate groups
What do kinases do?
Add phosphate groups
What state is glycogen synthase when it is dephosphorylated?
Active
What state is glycogen phosphorylase when phosphorylated?
Active
What does the glucagon/epinephrine signalling pathway do?
Starts phosphorylation cascae via cAMP
Activates glycogen phosphorylase
What does glycogen phosphorylase do?
Cleaves glucose residues off glycogen, generating glucose-1-phosphate
What does the insulin-signalling pathway do?
Increases glucose import into muscle
Stimulates the activity of muscle hexokinase
Activates glycogen synthase
When do amino acids undergo oxidative phosphorylation?
Normal synthesis and degradation of cellular proteins
Diet rich in proteins
Starvation or uncontrolled diabetes mellitus
Where is glutamate dehydrogenase found?
In the liver
What does glutamate dehydrogenase do?
Deamination of amino acids;
It releases the amino group from glutamate and produces α-ketoglutarate and ammonium
True or False:
The conversion of glutamate to α-ketoglutarate is irreversible
False
It is readily reversible
Which enzyme is responsible for the conversion of glutamate into other amino acids?
Amino transferase
What is transamination?
The transfer of an amino group from an amino acid to a α-ketoacid to create a new amino acid and a new α-ketoacid
What is the most common α-ketoacid?
α-ketoglutarate
What is responsible for the conversion of Glutamate into α-ketoglutarate?
Glutamate dehydrogenase
What two amino acids have the highest concentration in the blood?
Alanine and Glutamine
Why is ammonium converted to urea?
Ammonium ions are toxic to cells
How is ammonia transported from the muscles to the liver?
Glucose-alanine cycle;
The amine group is used to make glutamate which undergoes a tranamination reaction with pyruvate by alanine aminotransferase creating alanine and α-ketoglutarate. The alanine then travels through the blood until it is taken up by the liver where it undergoes a second transamination reaction with α-ketoglutarate by alanine aminotransferase back into pyruvate and glutamate. The amine group on the glutamate can the be removed and converted into urea for excretion and the pyruvate can undergo gluconeogenesis
What are elevated levels of uric acid caused by?
Purine-rich diet
Fasting and rapid weight loss
What two molecule link the citric acid cycle and urea cycle?
Aspartate and Fumarate
How many phosphates are consumed per urea formed?
3
How many NADH is produced from the fumarate created in the urea cycle?
1 NADH (which is worth 2.5 ATP)
What is the breakdown product of creatine phosphate?
Creatinine
What is the main source of energy for the brain when in starvation?
Ketone bodies
What happens to human metabolism immediately after a meal?
The high concentrations of blood-glucose causes insulin to be secreted which stimulated glycolysis and glycogen synthesis
What happens to human metabolism 2 hours after a meal?
Blood glucose levels begin to drop causing glucagon to be secreted which stimulates glycogen breakdown releasing glucose
What happens to human metabolism 4 hours after a meal?
More glucagon is released, TAG hydrolysis and fatty acid become fuel for the muscle and the liver
What happens to human metabolism during prolonged periods of fasting?
Muscles begin to be used for fuel; the liver deaminates or transaminates aas. The carbon skeletons are converted to pyruvate and then glucose via gluconeogenesis.
Fatty acids are converted to acetyl-CoA but cannot be converted to glucose since oxaloacetate is depleted so the acetyl-CoA is used to make ketone bodies
What are the three main classes of hormones?
Polypeptide/protein
Amine
Steroid
What class of hormone is insulin?
Polypeptide/protein
Which amino acids are amine hormones derived from?
Tyrosine and tryptophan
What class of hormone is epinephrine?
Amine
What are the two major types of intracellular proteins that act as molecular switches?
Phosphorylation
GTP binding
What are the major classes of receptors?
Ion channel coupled receptors
G-protein coupled receptors
Enzyme linked receptors
Nuclear receptors
How many transmembrane segments does a GPCR have?
7
How many subunits does a G-protein have?
3; alpha, beta and gamma
Which G-protein subunit is GDP bound when it is inactive?
Alpha
What two major effector enzymes can be activated through GPCRs?
Adenylate cyclase
Phospholipase C
Which second messenger is activated by adenylate cyclase?
cAMP
Which secondary messenger is activated by phosphlipase C?
DAG and IP3
What occurs in the Inositol phospholipid pathway?
The activated GPCR activates a G-protein which activates phospholipase C which causes the inositol phospholipid to separate into DAG and IP3. The IP3 then activates and ion-channel of the ER which releases Ca2+ into the cytosol which activates PKC
What occurs in the cyclic AMP pathway
The activated GPCR activates a G-protein which activates adenylate cyclase which converts ATP into cAMP. The cAMP can then bind to inactive PKA. When four cAMP molecule bind to the PKA it activates and separates into four, two of which are active PKA enzymes
How does the binding of a specific protein to the extracellular portion of a receptor tyrosine kinase activate the catalytic domain?
The protein binds to the inactive monomer causing it to interact with another monomer. The RTKs then start phosphorylating each other at the tyrosine kinase domain which generate binding sites for signalling proteins
How do proteins arrange around an activated receptor tyrosine kinase?
A docking protein binds with the phosphates on the receptor. An adapter protein then binds to a tyrosine phosphate of the docking protein with its SH2 domain. The two SH3 domains of the adapter protein bind to a Sos prtein and a scaffold protein respectively .
Both the docking protein and Sos protein are anchored to a phospholipid docking site via their PH domain
How do Ras GTPases cause signalling cascades with receptor tyrosine kinases?
The activated Sos protein interacts with inactive Ras protein. It causes the GDP bound to the Ras to be released and replaced with a GTP, activating the Ras protein
How do Ras proteins activate the MAPK pathway?
The active Ras activates a Raf kinase which activates the Mek kinase which activates the Erk kinase. All of these phosphorylations required a net input of ATP
What is responsible for activating PI3K?
Receptor tyrosine kinases
What is the alternate name for Akt?
Protein kinase B (PKB)
How does Akt promote cell survival?
It inhibits a protein called Bad, which encourages apoptosis
How does Bad encourage apoptosis?
Bcl2 is a protein that inhibits apoptosis. When bad is active it is bound to Bcl2 which inactivates it. Bad must be phosphorylated by Akt in order for it to be deactivated and release the Bcl2
What families of kinases are associated with Tyrosine-Kinase-Associated receptors?
Src Kinase Family
Janus Kinase Family
What occurs in the JAK/STAT pathway?
In its inactive state a JAK protein is bound to each of the cytokine receptor monomers. When a cytokine molecule causes the receptor to become a dimer the JAK proteins phosphorylate each other. They can then phsophorylate the receptor to allow a STAT protein to bind to the receptor. The active STAT proteins then form a dimer and enter the nucleus where they form a transcription regulatory complex
True or False:
Steroid receptors bind to DNA as homodimers
True
True or False:
RXR-NRs bind to DNA as heterodimers
True
Insulin stimulates glucose transport by:
Select one:
a. binding to the glucose transporters
b. moving glucose transporters to the cell membrane
c. increasing the affinity of glucose transporters for glucose
d. increasing the rate at which glucose moves through the glucose transporters
b. moving glucose transporters to the cell membrane
Glucokinase:
Select one:
a. acts in the conversion of liver glycogen to glucose 1-phosphate.
b. converts fructose-6-phosphate to glucose-6-phosphate.
c. converts glucose 6-phosphate to fructose 6-phosphate.
d. is a hexokinase isozyme found in liver cells
d. is a hexokinase isozyme found in liver cells
Allosteric enzymes:
Select one or more:
a. undergo activation or inhibition by compounds that bind at a site separate from the catalytic site.
b. undergo activation or inhibition by compounds that bind at a site separate from the catalytic site.
c. catalyse reactions that are crucial for regulation of metabolic pathways.
d. are composed of subunits that undergo conformational change between a more-active- and less-active-state.
A, B, C and D
all correct
There is more than one correct answer - choose all correct answers.
Which of the following statements are correct?
Select one or more:
a. Fructose-2,6-bisphosphate stimulates gluconeogenesis and inhibits glycolysis.
b. Fructokinase-1 and fructokinase-2 compete for the same substrate, fructose-6-phosphate
c. AMP activates PFK-1 while ATP inhibits it.
d. Glycolysis and gluconeogenesis are usually reciprocally regulated.
c. AMP activates PFK-1 while ATP inhibits it.
AND
d. Glycolysis and gluconeogenesis are usually reciprocally regulated.
Phosphofructokinase-1:
Select one or more:
a. is stimulated by fructose-2,6-bisphosphate.
b. is an enzyme of the gluconeogenesis pathway.
c. is inhibited by ATP.
d. synthesises fructose-2,6-bisphosphate.
e. is stimulated by ATP.
a. is stimulated by fructose-2,6-bisphosphate.
AND
c. is inhibited by ATP.
Which of the following is true of glycogen synthesis and breakdown?
Select one:
a. Phosphorylation activates the enzyme responsible for breakdown, and inactivates the synthetic enzyme.
b. Phosphorylation activates the enzyme responsible for synthesis, and inactivates the breakdown enzyme.
c. Synthesis is catalysed by the same enzyme that catalyses breakdown.
d. The immediate product of glycogen breakdown is free glucose.
e. Under normal circumstances, glycogen synthesis and glycogen breakdown occur simultaneously and at high rates.
a. Phosphorylation activates the enzyme responsible for breakdown, and inactivates the synthetic enzyme.
Non-essential amino acids:
Select one:
a. are not utilised in mammalian proteins.
b. can be synthesised in humans
c. are synthesised by plants and bacteria, but not by humans.
d. may be substituted with other amino acids in proteins.
e. must be provided by the diet in humans.
b. can be synthesised in humans
Choose the correct statement.
Select one or more:
a. Fumarate, which is released in the urea cycle returns to the mitochondria where it enters the citric acid cycle.
b. Fumarate is released in the citric acid cycle and enters the urea cycle.
c. Aspartate, one of the products of the urea cycle is then used in the citric acid cycle.
d. Citrulline, a product of the citric acid cycle is used as a product of the urea cycle.
a. Fumarate, which is released in the urea cycle returns to the mitochondria where it enters the citric acid cycle.
Choose all correct answers.
Nucleotides have numerous cellular functions, including:
Select one or more:
a. ATP as a source of chemical energy
b. dCTP as a substrate for DNA synthesis
c. NAD+ as an enzyme cofactor
d. dTT as a substrate for RNA synthesis
a. ATP as a source of chemical energy
AND
b. dCTP as a substrate for DNA synthesis
AND
c. NAD+ as an enzyme cofactor
Lesch-Nyhan Syndrome is cause by deficiencies of which defects in nucleotide metabolism?
Hypoxanthine-guanine phophoribosyltransferase deficiency
Severe Combined Immunodeficiency (SCID) is cause by deficiencies of which defects in nucleotide metabolism?
Adenosine deaminase deficiency
A shift from the fasting state to the starvation state results in:
Select one:
a. decreased breakdown of triacylglycerols in adipocytes
b. decreased plasma fatty acids.
c. increased gluconeogenesis in the liver.
d. increased use of ketones as a source of energy by the brain.
d. increased use of ketones as a source of energy by the brain.
The largest energy reserve (in terms of kilojoules) in humans is:
Select one:
a. blood glucose.
b. liver glycogen
c. muscle glycogen
d. adipose tissue triacylglycerol
e. muscle protein
d. adipose tissue triacylglycerol
The order of polypeptide hormone control is:
Select one:
a. hypothalamus/CNS/ pituitary/ secondary targets
b. CNS/pituitary/hypothalamus/secondary targets
c. CNS/hypothalamus/pituitary/secondary targets
d. CNS/primary targets/pituitary/hypothalamus
c. CNS/hypothalamus/pituitary/secondary targets
Which statement about amine hormones is correct?
Select one:
a. Do not require enzymes for their synthesis
b. Are made from tyrosine and tryptophan
c. Only circulate in the bloodstream at very high levels
d. They are only derived from tryptophan
b. Are made from tyrosine and tryptophan
Which is not a general property of cell receptors:
Select one:
a. Have high affinity binding sites for hormones
b. Are specific for only certain types of hormones
c. Released from cells on hormone binding
d. Can be found in the cell membrane
c. Released from cells on hormone binding
Protein kinase A is a downstream effector kinase of which second messenger: Select one: a. IP3 b. GDP c. cGMP d. Diacyl glycerol e. cAMP
e. cAMP
Nuclear receptor signalling within a cell generally requires:
Select one:
a. targeting of nuclear receptors to the mitochondria
b. activation of tyrosine kinase adaptor proteins
c. dimerization and translocation of nuclear receptors to the nucleus
d. the binding of lipid hormones to the cell surface
c. dimerization and translocation of nuclear receptors to the nucleus
Which of the following statements regarding GPCRs is TRUE?
Select one:
a. GPCRs bind hormones inside the cell
b. On activation they interact with a trimeric G-protein complex
c. Only peptides or proteins can bind to GPCRs
d. GPCRs are anchored in the plasma membrane by a single alpha-helical transmembrane sequence
b. On activation they interact with a trimeric G-protein complex
The Janus family kinases associate with which type of enzyme-linked receptors?
Select one:
a. Receptor tyrosine phosphatases
b. Receptor serine/threonine kinases
c. Tyrosine-kinase-associated receptors
d. Receptor tyrosine kinases
c. Tyrosine-kinase-associated receptors
Hormones are divided into which of the three following classes:
Select one:
a. Proteins/peptides, amines, neurotransmitters
b. Polypeptides/proteins, imines, neurotransmitters
c. Polypeptides/proteins, amines, lipophilic
d. Peptides, amines, nuclear receptors
c. Polypeptides/proteins, amines, lipophilic
In the Cyclic AMP second messenger pathway, which enzyme functions as an effector enzyme leading to the activation of a second messenger?
Select one:
a. Diacyglycerol
b. Adenylate cyclase
c. PKA
d. Phospholipase C
b. Adenylate cyclase
Which of the following is the correct order of interaction in the MAP kinase pathway: Select one: a. GTP-Ras/Raf/Mek/Erk b. GTP-Ras/Erk/Mek/Raf c. Raf/Mek/Erk/GTP-Ras d. GTP-Ras/PLC/Raf/Mek
a. GTP-Ras/Raf/Mek/Erk
SH2/SH3 domain adaptor proteins are important because:
Select one:
a. They can couple phospho-tyrosine proteins together
b. They couple phospho-alanine proteins together
c. They phosphorylate other proteins in the growing cascade
d. All RTKs lack phospho-tyrosine domains
a. They can couple phospho-tyrosine proteins together
Choose the correct statement about nuclear receptors:
Select one:
a. they are always targeted to the nucleus by coactivator proteins
b. they are always present in the nucleus
c. they always bind DNA as heterodimers with RXR
d. they bind to specific short DNA sequences in the DNA of the nucleus
d. they bind to specific short DNA sequences in the DNA of the nucleus
What are allosteric effectors?
a molecule that bind to the allosteric site of an enzyme in order to regulate its activity
What is α-keto acid?
organic compounds that contain a carboxylic acid group and a ketone group. They are involved in the citric acid cycle and glycolysis
What is amino transferase?
enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid
What are coenzymes?
a non-protein compound that is necessary for the functioning of an enzyme
What is creatine phosphate?
a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle
What are creatinine?
a breakdown product of creatine phosphate in muscle
What is deamination?
the removal of an amino group from an amino acid or other compound
What is diabetes mellitus?
a disease in which the body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood and urine.
What are essential amino acids?
amino acids that cannot be made by the body and hence must be obtained through diet. There are 9 amino acids; histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine
What is feedback inhibition?
a process whereby the end product of a reaction interferes with the enzyme that helped produce it
What is glucagon?
a hormone found in the pancreas which promotes the breakdown of glycogen to glucose in the liver
What is glucokinase?
an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cell in the liver and pancreas
What is gluconeogenic tissue?
Tissue where gluconeogenesis, a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates, occurs
What is glucose-6-phosphatase?
an enzyme that hydrolyses glucose-6-phosphate resulting in the creation of a phosphate group and free glucose
What is glucose-6-phosphate?
a glucose sugar phosphorylated on carbon 6. G-6-P has many possible fates within the cell.
What is the glucose-alanine cycle?
the series of reaction in which amino groups and carbons from muscle are transported to the liver as alanine in exchange for glucose
What is glutamate dehydrogenase?
an enzyme required for urea synthesis that converts glutamate to α-ketoglutarate, and vice versa.
What is glycogen phosphorylase?
an enzyme that catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond
What is glycogenesis?
the formation of glycogen from sugar
What is glycogenolysis?
the breakdown of glycogen (n) to glucose-6-phosphate and glycogen (n-1)
What is hexokinase?
an enzyme that phosphorylates hexoses, particularly glucose into glucose-6-phosphate
What is hyperglycaemia?
an abnormally high blood pressure
What is insulin?
a peptide hormone produced by beta cells of the pancreatic islets that regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into liver, fat and skeletal muscle cells
What are isozymes?
each of two or more enzymes with identical function but different structure
What is ketoacidosis?
a pathological metabolic state whereby
the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased
What is a kinase?
an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate donating molecules to specific substrates
What is negative nitrogen balance?
a state whereby the amount of nitrogen excreted from the body is greater than the amount of nitrogen ingested. It is associated with burns, serious tissue injuries, fevers, hyperthyroidism, wasting diseases, and during periods of fasting
What is nitrogen balance?
a measure of nitrogen input minus nitrogen output
What are non-essential amino acids?
anamino acidthat can be made by humans and so is notessentialto the human diet. There are 11nonessential amino acids: alanine, arginine, asparagine, asparticacid, cysteine, glutamicacid, glutamine, glycine, proline, serine, and tyrosine.
What is oxidative phosphorylation?
the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH2to O2by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms
What is a phosphatase?
an enzyme that cleave a phosphate group from a protein
What is positive nitrogen balance?
a state whereby the intake of nitrogen into the body is greater than the loss of nitrogen from the body, so there is an increase in the total body pool of protein. It is associated with periods of growth, hypothyroidism, tissue repair and pregnancy.
What is pyruvate kinase?
the enzyme that catalyzes the final step of glycolysis. It converts phosphoenolpyruvate and ADP into pyruvate and ATP
What is transamination?
a chemical reaction that transfers an amino group to a ketoacid to form new amino acids
What is urea?
a colourless crystalline compound which is the main nitrogenous breakdown product of protein metabolism in mammals and is excreted in urine
What is the urea cycle?
a cycle of biochemical reactions that produces urea from ammonia (NH3). Theurea cycleconverts highly toxic ammonia to urea for excretion
What is uric acid?
an almost insoluble compound that is a breakdown product of nitrogenous metabolism. It is the main excretory product in birds, reptiles, and insects
What are zymogens?
an inactive enzyme which is converted into an active enzyme when altered by another enzyme
What is adenylate cyclase?
an enzyme that catalyses the conversion of ATP into cAMP and pyrophosphate
What is the adrenal cortex?
the outside part of the adrenal gland that produces hormones that are vital to life, such as cortisol (which helps regulate metabolism and helps your body respond to stress) and aldosterone (which helps control blood pressure)
What is adrenaline?
a hormone secreted by the adrenal glands that increases rates of blood circulation, breathing, and carbohydrate metabolism and prepares muscles for exertion
What is Akt?
a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. Also known as Protein kinase B (PKB)
What is aldosterone?
a corticosteroid hormone which stimulates absorption of sodium by the kidneys and so regulates water and salt balance
What are androgens?
any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics by binding to androgen receptors. Androgens are synthesised in the testes, ovaries and the adrenal glands
What is autophosphorylation?
a type of post-translational modification of proteins. It is generallydefinedas the phosphorylation of the kinase by itself
What is Bad?
a pro-apoptotic protein. When it is phosphorylated by PKB it forms a heterodimer preventing it from stopping other proteins from carrying out apoptosis
What is cAMP?
a second messenger important in many biological processes including signal transduction within a cell
What is a cell-surface receptor?
receptor molecules that are anchored to the outside of the cell membrane. They convert extracellular signals into intracellular signals
What is cortisol?
a steroid hormone produced in the adrenal cortex in response to stress and low blood-glucose concentration
What is Cushing syndrome?
a series of symptoms caused by chronic exposure to cortisol. These symptoms include weight gain, hypertension, diabetes, osteoporosis, muscle weakness and decreased growth in children
What is the cAMP pathway?
a G protein-coupled receptor-triggered signalling cascade used in cell communication
What are cytokine receptors?
cell-surface glycoproteins that bind specifically tocytokinesand transduce their signals. Thesereceptorsenable cells to communicate with the extracellular environment by responding to signals generated in the vicinity or in other parts of the organism
What does endocrine mean?
relating to or denoting glands which secrete hormones or other products directly into the blood
What is a enzyme-coupled receptor?
a transmembranereceptor, where the binding of an extracellular ligand causes enzymaticactivity on the intracellular side. Hence a catalyticreceptoris an integral membrane protein possessing bothenzymaticcatalytic andreceptor functions
What are enzyme-linked receptors?
a transmembranereceptor, where the binding of an extracellular ligand causes enzymaticactivity on the intracellular side. Hence a catalyticreceptoris an integral membrane protein possessing bothenzymaticcatalytic andreceptor functions. Also known as a catalytic receptor
What is a G-protein coupled receptors (GPCRs)?
the largest and most diverse group of membranereceptorsin eukaryotes. These cell surface receptorsact like an inbox for messages and activate internal signal transduction pathways in response to messengers such as light energy, peptides, lipids, sugars, andproteins
What is a glucocorticoid?
a class of corticosteroid which is a subset of steroid hormones. Glucocorticoids are responsible for regulating glucose metabolism and are synthesised in the adrenal cortex
What are growth factors?
a substance, such as a vitamin or hormone, which is required for the stimulation of growth in living cells
What is a heterodimer?
a dimer composed of two different proteins
What is a homodimer?
a dimer composed of two of the same proteins
What is the hypothalamus?
a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of thehypothalamusis to link the nervous system to the endocrine system via the pituitary gland
What is insulin?
a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into liver, fat and skeletalmuscle cells
What is a intracellular recepor?
receptors located inside the cell rather than on its cell membrane
What are ion channel coupled receptors?
cell membrane boundreceptors. They act through synaptic signaling on electrically excitable cells and convert chemical signals (ligand) to electrical ones. It is essential in neuronal activities.Ion-channel-linked receptorsare also called ligand-gatedchannels.
What is the janus kinase family?
a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway
What is a lipophillic hormone?
a type of hormone that is able to pass through the cell and nuclear membrane in order to reach their target receptor that may be on the surface or inside of the cell. These include steroid and thyroid hormones
What is the MAPK pathway?
a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell
What is a mineralocorticoid?
a class of corticosteroid which are a subset of steroid hormones. Mineralcorticoids are produced in the adrenal cortex and influence salt and water balances
What is a nuclear receptor?
a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules
What does paracrine mean?
relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it.
What is a peptide-amine hormone?
a type of hormone derived from the amino acids tyrosine or tryptophan which are synthesised in the adrenal medulla (and CNS) which are secreted in response to signals from the CNS. These hormones have a very short lifespan (seconds) and include epinephrine and norepinephrine
What is the PH domain?
a protein domain of proteins involved in intracellular signalling which can bind βγ-subunits of heterotrimeric G proteins and PKC
What is a phosphinositide 3-kinase (PI3K)?
a family ofenzymesinvolved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.
What is PKB?
an enzyme that plays a major role in signal transduction. Also known as Akt
What is a polypeptide hormone?
a type of hormone that is stored in vesicles (for up to 1 day), many of which are stored as a prohormone. They are released by exocytosis and circulate the blood stream for a few minutes. Insulin and glucagon are both examples
What is a prohormone?
a physiologically inactive precursor of a hormone
What are Ras proteins?
a family of relatedproteinswhich is expressed in all animal cell lineages and organs. AllRas proteinfamily members belong to a class ofproteincalled small GTPase, and are involved in transmitting signals within cells (cellular signal transduction)
What is a receptor tyrosine kinase?
the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types ofcancer.
What are second messengers?
a substance whose release within a cell is promoted by a hormone and which brings about a response by the cell. These include cAMP and diacylglycerol (DAG)
What is a SH2 domain?
a structurally conserved protein domain contained within many intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins.
What is a SH3 domain?
a protein domain found within many intracellular signal-transducing proteins.
The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases SH3 proteins usually bind far away from theactive site
What is signal transduction?
A set of chemical reactions in a cell that occurs when a molecule, such as a hormone, attaches to a receptor on the cell membrane. The pathway is actually a cascade of biochemical reactions inside the cell that eventually reach the target molecule or reaction
What is the SRC kinase family?
a family of non-receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, modifying these proteins by phosphorylation of tyrosine residues
What is testosterone?
a steroid hormone that stimulates development of male secondary sexual characteristics, produced mainly in the testes, but also in the ovaries and adrenal cortex
What are zinc fingers?
Azinc fingeris a small protein structural motif that is characterized by the coordination of one or morezinc ions (Zn2+) in order to stabilize the fold.
