Term
| What is energy stored as if it is not mobilized? |
|
Definition
| Glycogen and Triacylgycerols |
|
|
Term
| What are the large lipoprotein particles and where are they packaged? |
|
Definition
|
|
Term
| When does the body lose weight/ gain weight? |
|
Definition
Lose weight: Energy in < Energy out
Gain weight: Energy in > Energy out |
|
|
Term
| What is the normal range of blood glucose? |
|
Definition
|
|
Term
| Where is pro-insulin stored? |
|
Definition
| Vesicles in the B-cells of the pancreas |
|
|
Term
| What activates pro-insulin and how does it do this? |
|
Definition
Serine Proteases
They remove a polypeptide (C-peptide) from the middle of the pro-insuline to make a dipeptide |
|
|
Term
| How is glucose taken into the B-cells in order to release insulin? |
|
Definition
|
|
Term
| How does Glucose stimulate insulin release? |
|
Definition
| Taken up by GLUT2 and phosphorylated by GK to make G6P which forms a metabolite that releases Ca and makes insulin fuse with plasma membrane |
|
|
Term
| What cells produce glucagon and what stimulates its release? |
|
Definition
alpha cells
Low blood glucose levels |
|
|
Term
|
Definition
| Plasma membrane of Liver and Adipose cells. |
|
|
Term
| What does glucagon function through? |
|
Definition
| trimeric G-protein, adenylyl cyclase, cAMP, and PKA |
|
|
Term
| After hepatic cells replenish their glycogen stores, what happens to the remaining G6P? |
|
Definition
| Converted into fatty acids => esterfied to alpha-GP to form TAGs that are packaged into VLDLs (lipoprotein) then shipped to adipose |
|
|
Term
| What bonds hold glycogen together? |
|
Definition
| alpha-1-4 and alpha-1-6 glycosidic bonds and bound to Glycogenin |
|
|
Term
| What is the key enzyme in glycogenolysis? |
|
Definition
|
|
Term
| What converts G6P to G1P? |
|
Definition
|
|
Term
| What catalyzes G1P to UDP-glc? |
|
Definition
| UDP-glucose pyrophosphoylase |
|
|
Term
| What are the active and inactive forms of Glycogen Synthase? |
|
Definition
GS-a: active (dephosphorylated)
GS-b: inactive (phosphorylated) |
|
|
Term
| What phosphorylates GS in order to inactivated it? |
|
Definition
|
|
Term
| What dephosphorylates GS in order to activated it? |
|
Definition
| PP-ase 1 via Insulin action |
|
|
Term
| What does GS-b have a positive allosteric site for, and what does it do? |
|
Definition
| G6P in order to activate GS-b |
|
|
Term
| Where does fatty acid synthesis occur? |
|
Definition
| Cytosol of liver and adipose cells |
|
|
Term
| What are the substrates and products of FA synthesis? |
|
Definition
Substrate: 8 Acetyl-CoA
Product: Palmitate |
|
|
Term
| What process are used to convert G6P into cytosolic Acetyl-CoA for FA synthesis? |
|
Definition
Glycolysis
PDH
Citrate Shuttle |
|
|
Term
| What enzymes are needed for FA synthesis? |
|
Definition
Acetyl-CoA Carboxylase
Fatty Acid Synthase (FAS) |
|
|
Term
| What is the first process that G6P has to undergo in order to achieve FA synthesis? |
|
Definition
| G6P conversion into Pyr via glycolysis |
|
|
Term
| What allosterically inhibits PFK1 and PK? |
|
Definition
|
|
Term
| What overides the negative ATP modulation on PFK1? |
|
Definition
|
|
Term
| What overides the negative ATP modulation on PK? |
|
Definition
|
|
Term
| What are the two domains on the peptide responsible for F-2,6-BP? |
|
Definition
|
|
Term
| What form of the PFK-2 and F-2,6-BPase peptide complex produces F-2,6-BP? |
|
Definition
| Dephosphorylated form (PFK-2) |
|
|
Term
| What transports pyruvate into the matrix from the cytosol? |
|
Definition
|
|
Term
| What transports Citrae into the cytosol from the matrix? |
|
Definition
| tricarboxylic transporter |
|
|
Term
| What does citrate lyase cleave citrate into in the cytosol? |
|
Definition
|
|
Term
| What happens to the cytosolic OAA that builds up from FA synthesis? |
|
Definition
| Malate dehydrogenase converts the OOA into malate using NADH |
|
|
Term
| After cytosolic OAA is converted to malate, what happens to the malate? |
|
Definition
| Oxidatively decarboxylated to pyruvate by malic enzyme using NADP+, which then enters the matrix |
|
|
Term
| What is Acetyl-CoA Carboxylase dependent on? |
|
Definition
|
|
Term
| What is Acetyl-CoA Carboxylase responsible for? |
|
Definition
| Carboxylation of acetyl-CoA forming malonyl-CoA |
|
|
Term
| What is positive modulator of malonyl-CoA synthesis? |
|
Definition
|
|
Term
| What are the six enzymatic domains of FAS + the Acyl carrier protein? |
|
Definition
KS
MAT
DH
ER
KR
ACP
TE
Kind Men Don't Ever Kill Any Tigers |
|
|
Term
| How are the ACP-protein and coenzyme A similar? |
|
Definition
| They both contain the vitamin panthothenate |
|
|
Term
| What is the major pathway for generating NADH in cells? |
|
Definition
| Hexose MonoPhosphate Shunt (HMP Shunt) |
|
|
Term
| What are the two functions of the HMP shunt? |
|
Definition
Maintain high NADPH levels in cytosol (Oxidative Pathway)
Synthesize ribose-5-phosphate (R5P) for nt synthesis (Non-oxidative Pathway) |
|
|
Term
| What oxidizes G6P to 6PG? |
|
Definition
| G6PDH with NADP+ reduction |
|
|
Term
| What oxidatively decarboxylates 6PG to Ru5P? |
|
Definition
|
|
Term
| What is the net result of the HMP Shunt Oxidative Pathway? |
|
Definition
|
|
Term
| What is the major control of the HMP Shunt Oxidative Pathway? |
|
Definition
| cytosolic NADPH/NADP+ ratio |
|
|
Term
| What are the major enzymes of the HMP Shunt Non-Oxidative Pathway? |
|
Definition
| Transketolase and Transaldolase |
|
|
Term
| Which pathway in the HMP shunt is reversible? |
|
Definition
|
|
Term
| What is the benefit of the Non-oxidative HMP Shunt pathway being reversible? |
|
Definition
| You can use this as a salvage pathway to reconvert excess Ru5P into glycolytic pathway intermediates. |
|
|
Term
| What is the result of the Non-oxidative HMP shunt pathway? |
|
Definition
| 2 F6P and G3P (15 carbon) are converted into 3 R5P (15 carbon) |
|
|
Term
| Where does elongation or desaturation of palmityl-CoA occur? |
|
Definition
| At the membrane of smooth ER |
|
|
Term
| What enzyme complex elongates FAs? |
|
Definition
|
|
Term
| How can double bonds be inserted into FAs and where is this located? |
|
Definition
| Desturases (Monooxygenases) in the smooth ER membrane |
|
|
Term
| What do monooxygenases require, and where does it get its reducing power? |
|
Definition
require: cytochrome b5, cytochrome b5 reductase
Reducing power from: NADPH |
|
|
Term
| What four desturases occur in humans? |
|
Definition
| Δ4, Δ5, Δ6, and Δ9 desaturase. |
|
|
Term
| Where is the first double bond added in FAs? |
|
Definition
|
|
Term
| What is the starting compound for TAG synthesis? |
|
Definition
|
|
Term
| How do you obtain phosphatidate (PA) from αGP? |
|
Definition
| Esterfying two FAs to αGP. |
|
|
Term
| How do you get DAG from PA? |
|
Definition
| Removing a phosphate from PA |
|
|
Term
| How do you get TAG from DAG? |
|
Definition
|
|
Term
| Where are newly synthesized TAGs sent? |
|
Definition
| They are packaged into lipoprotein particles called VLDLs, which transport fat to the adipose. |
|
|
Term
| What enzyme is used to convert glycerol into αGP? |
|
Definition
|
|
Term
| What promotes the moving of GLUT4 receptors to the plasma membrane of muscles? |
|
Definition
| Increases in the Insulin/Glucagon ratio |
|
|
Term
| What will a rise in G6P cause? |
|
Definition
|
|
Term
| What is the key enzyme for glycogenolysis and what does it produce? |
|
Definition
Glycogen Phosphate (GP)
Produces G1P |
|
|
Term
| What enzyme is used to break down branches during glycogenolysis? |
|
Definition
|
|
Term
| What converts G1Ps into G6Ps? |
|
Definition
|
|
Term
| What needs to happen for G6P to be removed from the liver? |
|
Definition
| Phosphate group must be removed in the lumen by G6Pase |
|
|
Term
|
Definition
|
|
Term
| What transports Glucose into the cytosol of the liver cells? |
|
Definition
|
|
Term
| How does Glucose get from the hepatocyte cytosol into the blood? |
|
Definition
|
|
Term
| What are the two forms of GP? |
|
Definition
GPa: phosphorylated/active
GPb: dephosphorylated/inactive |
|
|
Term
| How is GPb converted into an active form? |
|
Definition
| Glycogen Phospho-ylase Kinase (GPK) |
|
|
Term
| What are the two forms of GPK? |
|
Definition
GPKa: phosphorylated/active
GPKb: dephosphorylated/inactive |
|
|
Term
| How does the inactive GPK become activated? |
|
Definition
| Phosphorylation via PKA or Ca binding allostericaly. |
|
|
Term
| How does PKA action on GS and GPK differ? |
|
Definition
PKA activated GPK when phosphorylated.
PKA inactivated GS when phosphorylated. |
|
|
Term
| Where does Gluconeogenesis occur (GNG)? |
|
Definition
| Cytosol of the liver and the kidneys during starvation. |
|
|
Term
| What is the result of GNG and what's required for it to occur? |
|
Definition
A molecule of G6P is created.
Two molecules of cytosolic OAA are used.
2ATP, 2GTP, 2NADHS are inputted. |
|
|
Term
| What are the two enzymes required in GNG to bypass the irreversible steps of Glycolysis? |
|
Definition
|
|
Term
| What enzyme in GNG is needed to bypass the Pyruvate Kinase step of Glycolysis? |
|
Definition
|
|
Term
| What does PEPCK cause in GNG? |
|
Definition
| OAA converted to PEP via GTP usage |
|
|
Term
| What is the irreversible step in glycolysis that is overcome via F1,6BPase in GNG? |
|
Definition
|
|
Term
| What does F1,6BPase cause in GNG? |
|
Definition
| F1,6BP is converted to F6P |
|
|
Term
| What negatively modulates F1,6BPase? |
|
Definition
F2,6BP
(has an allosteric binding site and causes positive modulation of PFK1) |
|
|
Term
| What are the major controls to GNG? |
|
Definition
PFK1 and PK => both inhibited by ATP
PK also inhibited by alanine |
|
|
Term
| Why is PK more susceptible to negative modulation? |
|
Definition
| It is phosphorylated by PKA |
|
|
Term
| What are the major sources of carbon for GNG? |
|
Definition
|
|
Term
| How do low levels of insulin affect proteins? |
|
Definition
Insulin promotes amino acid uptake by muscle and protein synthesis.
Low insulin levels leads to net breakdown of protein in muscle. |
|
|
Term
| What happens to pyruvate during muscle contraction? |
|
Definition
| Transaminated using ALT and glutamate into alanine. |
|
|
Term
| What must happen in order to use the carbons of amino acids for GNG? |
|
Definition
| The amino groups must be removed and detoxified via the urea cycle. |
|
|
Term
| How are amino groups removed from amino acids? |
|
Definition
| Transamination with aminotransferases |
|
|
Term
| Who receives the amino group from the amino acids? |
|
Definition
|
|
Term
| What must happen to the nitrogen from the amino groups in order for Urea Synthesis to occur? |
|
Definition
| They must be converted to equal amounts of ammonia and aspartate. |
|
|
Term
| How do α-keto acid get converted into OAA? |
|
Definition
|
|
Term
| How does the OAA of the matrix get transferred to the cytosol? |
|
Definition
| It gets converted into equal amounts of aspartate and malate, which can cross the IMM |
|
|
Term
| What can Malate and aspartate be used for? |
|
Definition
Asparatate: GNG, Urea Cycle
Malate: GNG |
|
|
Term
| What does aspartate become after it donates its nitrogen for urea synthesis? |
|
Definition
|
|
Term
| How is fumarate converted into malate? |
|
Definition
|
|
Term
|
Definition
| It is a surface protein that stabilizes TAG droplets. |
|
|
Term
| How are TAG stores mobilized? |
|
Definition
Decrease Insulin
Increased Glucagon |
|
|
Term
| How does epinephrine promote Glucagon mobilization? |
|
Definition
|
|
Term
| What does PKA phosphorylate to promote the hydrolysis of TAGs? |
|
Definition
|
|
Term
| Where does ketogenesis occur? |
|
Definition
|
|
Term
| When OAA is at low levels in the liver due to GNG, what happens to acetyl-CoA? |
|
Definition
| It is converted into a water-soluble form of energy, Ketone Bodies. |
|
|
Term
| What is the role of thiolase in Ketogenesis? |
|
Definition
| It condenses two acetyl-CoA into acetoacetyl-CoA |
|
|
Term
| What is the role of HMG-CoA synthesis in Ketogenesis? |
|
Definition
| Adding another Acetyl-CoA to acetoacetyl-CoA to form HMG-CoA |
|
|
Term
| What is the role of HMG-CoA lyase in Ketogenesis? |
|
Definition
| It removes an acetyl-CoA from HMG-CoA to give acetoacetate. |
|
|
Term
| How is NAD+ regenerated in Ketogenesis for β-oxidation? |
|
Definition
| acetoacetate is reduced to β-hydroxybutyrate |
|
|
Term
| What causes the reduction of acetoacetate to β-hydroxybutyrate? |
|
Definition
|
|
Term
| What is the ketone body concentration and fatty acid concentration in the blood during stage 1 of starvation? |
|
Definition
Ketone: 3 mM
Fatty Acid: 1-2mM |
|
|
Term
| How much has nitrogen excretion in the urine increased during stage 1 of starvation? |
|
Definition
|
|
Term
| What is the body living off of during stage 1 of starvation? |
|
Definition
|
|
Term
| Around what day does the brain start to oxidize ketone bodies? |
|
Definition
|
|
Term
| What is released when the brain starts to oxidize protein bodies? |
|
Definition
|
|
Term
| What are the results of the release of insulin during stage 1 of starvation? |
|
Definition
| Blood glucose drops to 2.5-3 mM due to a decrease in protein hydrolysis and amino acid release. |
|
|
Term
| Where do the fatty acid and ketone body concentrations level off near the end of stage 1 of starvation? |
|
Definition
Fatty acid: 2 mM
Ketone: 7mM |
|
|
Term
| What does the body live off primarily during stage 2 of starvation? |
|
Definition
|
|
Term
| What adjustment does the body making during stage 2 of starvation? |
|
Definition
|
|
Term
| How long will the body stay in stage 2 of starvation? |
|
Definition
| As long as there are fat stores, fatty. |
|
|
Term
| What is the only source of energy during stage 3 of starvation? |
|
Definition
|
|
Term
| What is being released from the tissues during stage 3 of starvation at a high rate? |
|
Definition
|
|
Term
| Where does GNG occur during stage 3 of starvation? |
|
Definition
|
|
Term
| What are the blood glucose and ketone body ranges for Type I diabetes and why? |
|
Definition
Glucose: 20-40 mM
Ketone: 17-18 mM
The body thinks it's in starvation mode. |
|
|
Term
| What are the three chemical reaction that occur during type I diabetes that play a role in clinical complication? |
|
Definition
Glycation of proteins
Polyalcohol formation
Decreased uptake of inositol by cells |
|
|
Term
| What forms when glucose is exposed to ε-amino group of lysines? |
|
Definition
|
|
Term
| In type I diabetes, what will tissues that contain aldose reductase convert aldose into? |
|
Definition
| Corresponding polyalcohol that cannot leave the cell, so water is drawn into it. |
|
|
Term
| In type I diabetes, what does glucose compete with in plasma membranes of cells? |
|
Definition
|
|
Term
| What does glucose competition with inositol cause? |
|
Definition
| Decreased synthesis of PI for the membrane and PI3 for signalling. |
|
|
Term
| What are the sources of the free amino acids? |
|
Definition
1. Dietary proteins
2. Turn-over of endogenous cellular proteins
3. Nonessential amino acids synthesized by cells using metabolic alpha-ketoacid intermidiated. |
|
|
Term
| What are the free amino acids in the body used by cells for? |
|
Definition
1. Proteins Synthesis
2. Small, N-containing molecule Synthesis
3. E and CO2 Production
4. Glucose and FA synthesis |
|
|
Term
| What are the essential amino acids? |
|
Definition
PVT TIM HALL
phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, arginine*, leucine, lysine, selenocysteine** |
|
|
Term
| Why is arginine conditionally essential? |
|
Definition
| It can be synthesized via the urea cycle |
|
|
Term
| What is a glucogenic amino acid? |
|
Definition
| Amino acid that can be converted into pyruvate or one of the TCA cycle intermediates. |
|
|
Term
| What is a ketogenic amino acid? |
|
Definition
| Amino acids that can be metabolized into acetyl-CoA or accetoacetyl-CoA, then into Ketone Bodies |
|
|
Term
| What amino acids are strictly glucogenic? |
|
Definition
Aspartate
Methionine
Arginine
AMA |
|
|
Term
| What amino acids are strictly ketogenic? |
|
Definition
|
|
Term
| What amino acids are both glucogenic and ketogenic? |
|
Definition
| Phenylalanine, Isoleucine, Tryptophan, Tyrosine |
|
|
Term
| How does aminotransferase work? |
|
Definition
Removes α-amino group from substrate amino acid, converting it to the corresponding α-ketoacid.
Amino group give to α-ketogluterate to make glutamate. |
|
|
Term
| What do aminotransferases use as the amino group acceptor to produce glutamate? |
|
Definition
|
|
Term
| True or False: ALL amino transferases use a specific α-amino acid as the amino group donor. |
|
Definition
False:
All branched chain α-amino acid have the same aminotransferase. |
|
|
Term
| What do aminotransferases require as the coenzyme? |
|
Definition
| Pyridoxalphosphate (B6 derived) |
|
|
Term
| What is pyridoxalphosphate (PLP) derived from? |
|
Definition
|
|
Term
| Why does B6 metabolism deficiencies cause aminotransferase deficiencies? |
|
Definition
| Pyridoxalphosphate is derived from B6 and acts as a coenzyme for aminotransferases. |
|
|
Term
| What are the three branched chain amino acids? |
|
Definition
Leucine
Isoleucine
Valine |
|
|
Term
| What is the typical direction that Glutamate DH reacts towards? |
|
Definition
|
|
Term
| When does Glutamate DH favor the production of glutamate from αKG? |
|
Definition
| When there are toxic levels of ammonia so that αKG and ammonia can react to form glutamate and detoxify ammonia while slowing the TCA cycle. |
|
|
Term
| Why would Vitamin B12 deficiency cause anemia? |
|
Definition
| Methionine Synthase will lose functioning and will cause a reduced RBC production. |
|
|
Term
| Why does blocking homocysteine to methionine cause cell division problems? |
|
Definition
| N10-formyl-THF and N5,N10-methylene-THF are blocked causing DNA replication issues |
|
|
Term
| Purine formation would be prevented by a deficiency in what folate molecule? |
|
Definition
|
|
Term
| Megaloblastic Anemia with neuropathy (pernicious megaloblastic anemia) is caused by what deficiency? |
|
Definition
|
|
Term
| Why does folate deficiency not cause neuropathy? |
|
Definition
| Folate deficiency alone causes no neuropathy because the brain can prioritize the use of folate so only bone marrow suffers. |
|
|
Term
| Methylmalonyl-CoA is responsible for the catabolism of what two branched amino acids? |
|
Definition
|
|
Term
| Why does Vitamin B12 cause methylmalonic acidura? |
|
Definition
| Methylmalonyl-CoA Mutase is vitamin B12 dependent and methylmalonyl is an intermediate of B-oxidation and is used for the catabolism for valine and isoleucine. |
|
|
Term
| What is the initial treatment for a patient with hyperhomocysteinemia? |
|
Definition
| Vitamin B6, B12, folic acid supplements. |
|
|
Term
| What is betaine a treatment for and how? |
|
Definition
Hyperhomocysteine.
Acts as a methyl donor |
|
|
Term
| How can you treat hyperhomocysteine if MS is deficient? |
|
Definition
| Betaine -> converts homocysteine to cysteine in the absence of Vit B12 and 5-methyl-THF |
|
|
Term
| What is the most common cause of homocystinuria? |
|
Definition
|
|
Term
|
Definition
| Elevated homocystine urine levels |
|
|
Term
| What causes Maple Syrup Urine Disease? |
|
Definition
| Deficiencies in branched-chain α-KA DH |
|
|
Term
| What are the characteristics of Maple Syrup Urine Disease? |
|
Definition
| High levels of branched chain α-KA in blood and urine (smells like maple syrup) |
|
|
Term
| What happens with MSUD if untreated? |
|
Definition
| Neurological problems and high mortality rates if branched chain amino acids are not avoided. |
|
|
Term
| What are the coenzymes for Branched-chain αKA DH? |
|
Definition
Thiamine pyrophosphate (Vit B1)
Lipoic Acid
Coenzyme A (Pantothetic acid)
FAD (riboflavin, Vit B2)
NAD+ (niacin, Vit B3) |
|
|
Term
| Why does phenylalanine deficiency make tyrosine an essential amino acid? |
|
Definition
| Phenylalanine can be made into tyrosine via Phenylalanine Hydroxylase. |
|
|
Term
| What will a deficiency in Phenylalanine Hydroxylase cause? |
|
Definition
| Elevation in phenylalanine that goes into the brain and causes PKU |
|
|
Term
| What does secondary tyrosine deficiency in PKU cause? |
|
Definition
| Deficiency in pigmentation |
|
|
Term
| The uptake of what amino acids are caused by PKU? |
|
Definition
|
|
Term
| What inhibition does Phe cause on LAT1 in PKU? |
|
Definition
|
|
Term
| What should PKU patients avoid aspartame? |
|
Definition
| It can be hydrolyzed into aspartate and pheylalanine at acidic pH |
|
|
Term
|
Definition
| Deficiencies of homogentisate oxygenase, which causes high homogentisate levels in the blood and urine. |
|
|
Term
|
Definition
| Oxidized form of homogentisate that appear during AKU patients. |
|
|
Term
| You have a patient who comes in with joint pain and small black/blue deposits in the sclera of his eye. You leave his urine sample out in the open, then return to find it turned blue. Why is this and what disease does it point towards? |
|
Definition
High levels of homogentisate can be oxidized to benzoquinones, which are blue.
This patient has AKU
|
|
|
Term
| How will Vitamin B12 deficiency affect the allergic response? |
|
Definition
| Histamine formation is dependent on Vitamin B12 (PLP). Without it, Hisitidine decarboxylase cannot function. |
|
|
Term
| Why do Folate deficient patients have a positive FIGlu test? |
|
Definition
| Histidine can be metabolized to Glutamate with a folate dependent mechanism. If Folate is deficient, the intermediate FIGlu will show up on the urine test. |
|
|
Term
| What causes Stiff-Man Syndrome? |
|
Definition
| Vitamin B6 deficiency or Glutamate Decarboxylase antibodies causing GABA deficiency. |
|
|
Term
| Why does Vitamin B6 cause Stiff-Man syndrome? |
|
Definition
Glutamate Decarboxylase requires PLP (Vitamine B6) to create GABA.
Thus, GABA is deficient. |
|
|
Term
| What is Niacin (Vit B3) a precursor for? |
|
Definition
|
|
Term
| What are the symptoms of Pellegra? |
|
Definition
3D's
Dermatitis
Diarrhea
Dementia |
|
|
Term
| What will insufficient intake/absorption of niacin and tryptophan cause? |
|
Definition
| Hypoproteinemia and Pellegra symptoms. |
|
|
Term
| Why does excess amounts of leucine intake cause Pellegra? |
|
Definition
| It causes niacin deficiency by preventing tryptophan conversion to niacin due to competitive inhibition. |
|
|
Term
| What amino acids are elevated and what amino acids remain the same in Hartnup Disease urine/fecal tests? |
|
Definition
Elevated: Neutral Amino Acids
Same: Proline, Hydroxyproline, Arginine |
|
|
Term
| What is Tyrosine a precursor for? |
|
Definition
| Melanin, Dopamine, Catecholamines |
|
|
Term
| What deficiency causes Oculocutaneous Albinism? |
|
Definition
|
|
Term
| What is deficient in Parkinsons Disease? |
|
Definition
Tyrosine Hydroxylase/BH4 deficiency
Dopa Decarboxylase deficiency
Dopamine-producing neuron loss |
|
|
Term
| For Parkinsons, why does L-dopa administration only help those who lost dopamine neurons or have tyrosine hydroxylase deficiencies? |
|
Definition
Dopa is a precursor to Dopamine via Dopa decarboxylase.
If Dope decarboxylase is deficient, Dopamine won't be produced. |
|
|
Term
| What deficiency causes Tyrosinemia? |
|
Definition
| Fumarylacetoacetate hydrolase deficiency |
|
|
Term
| What builds up in Tyrosinemia? |
|
Definition
|
|
Term
| Why is succinyl-acetone toxic? |
|
Definition
| It inhibits δ-ALA dehydratase in heme synthesis, causes a neurotoxic buildup of δ-ALA. |
|
|
Term
| Which is lipid soluble and can diffuse accross membranes - NH3 or NH4+? |
|
Definition
|
|
Term
| What does intracellular increase of NH3 cause? |
|
Definition
| Alkalization and Raised resting membrane potential |
|
|
Term
| What is the ammonia hypothesis of neuronal toxicity of hyperammonemia? |
|
Definition
1. Alkalosis due to NH4
2. αKG->glutamate leads to decreased TCA/E
3. Glutamate->Glutamine in astrocytes->osmotic damage/edema/hypertension |
|
|
Term
| What are the three identified glutamate receptors? |
|
Definition
|
|
Term
| How does the Glutamate and NMDA receptor hypothesis explain acute and chronic hyperammonemia? |
|
Definition
Acute: High glutamate leads to over active NMDAR and death
Chronic: Causes down-regulation of NMDAR, leading to brain dysfunction. |
|
|
Term
| How does Flumazenil reduce neurotoxicity of hyperammonia at early stages in some patients? |
|
Definition
| It acts as a benzodiazepine antagonist |
|
|
Term
| How does the GABA-benzodiazepine hypothesis explain neurotoxicity in hyperammonemia? |
|
Definition
| Dysregulation due to overstimuation of GABA-ergic inhibitory neuron transmission in CNS due to elevated levels of GABA, benzo antagonists, and neurosteroids |
|
|
Term
| What are the regulators of the Urea Cycle? |
|
Definition
Arginine allosterically activates NAG synthase
NAG allosterically activates CPS-1 |
|
|
Term
| Why does someone with Organic aciduria have secondary hyperammonemia? |
|
Definition
| They produced propionyl-CoA, methylmalonyl-CoA, and Valproyl-CoA to competitively inhibit NAG synthase |
|
|
Term
| How do patients with kidney failure develop hyperammonemia? |
|
Definition
They have elevated plasma urea levels => more urea diffuses to the intestines.
Bacterial urease breaks down into ammonia and release to the blood. |
|
|
Term
| How does antibiotic administration help patients with hyperammonemia due to kidney failure? |
|
Definition
| It reduces the intestine bacteria, thus lowering the amount of intestinal urease producing ammonia. |
|
|
Term
| How does lactulose treat hyperammonemia? |
|
Definition
It is metabolized by bacteria in the large intestine into lactic acid, which lowers the pH.
This causes the ammonia to be protonated and so it can not cross the intestinal lumen.
Ammonia net flow into intestinal lumen from blood. |
|
|
Term
| How does Valproic acid exposure affect the urea cycle? |
|
Definition
| It causes inhibition of CPS1 and inhibits the urea cycle |
|
|
Term
| If a patient has a urea cycle defect, what do you expect to be elevated in their serum (aside from ammonia, stupid)? |
|
Definition
| Glutatmine and urea-cycle intermediates |
|
|
Term
| What is the cause of HHH syndrome? |
|
Definition
A defect in the ORNT transmitter (mitochondrial ornithine transporter 1)
|
|
|
Term
| Why does homocitrulline levels rise in HHH syndrome? |
|
Definition
| In the absence of mitochondrial ornithine, OTC converts lysine to homocitulline and homocitrullinuria. |
|
|
Term
| What deficiency in the Urea Cycle causes Adult-Onset Type II Citrullemia (CTLN2)? |
|
Definition
| Arginosuccinate synthetase |
|
|
Term
| What are the plasma characteristics of adult-Onset Type II Citrullemia (CTLN2)? |
|
Definition
Elevated: citrulline, ammonia
Decreased: Arginine |
|
|
Term
| What is the protein that is mutated in Adult-Onset Type II Citrullemia (CTLN2) and what is it resposible for? |
|
Definition
| Citrin: transports aspartate out of the mitochondria and glutamate into the mitochondria. |
|
|
Term
| What causes Orotic Aciduria? |
|
Definition
| Buildup in orotic acid as a de nevo pyrimidine nucleotide synthesis byproduct due to defects in Urea Cycle enzymes (except CPS1). |
|
|
Term
| How does sodium phenylacetate and sodium benzoate help hyperammonemia? |
|
Definition
Phenylacetate: reacts with glutamine to form phenylacetylglutamine
Sodium benzoate: reacts with glycine to form hippuric acid |
|
|
Term
| Where are the highest quantities of heme synthesized? |
|
Definition
|
|
Term
| What is used as the precursor of heme synthesis? |
|
Definition
8 molecules Succinyl-CoA
8 molecules Glycine |
|
|
Term
|
Definition
| A cyclic tetrapyrrole with ferrous iron (Fe2+) in the center |
|
|
Term
| Where does heme synthesis occur? |
|
Definition
| In most cells with a mitochondria |
|
|
Term
| What is the rate limiting enzyme of heme synthesis? |
|
Definition
|
|
Term
| Which ALAS is autosomal and which is x-chromosome linked? |
|
Definition
ALAS1: autosomal
ALAS2: x-linked |
|
|
Term
| Where are ALAS 1 and ALAS 2 expressed? |
|
Definition
ALAS1: Liver
ALAS2: Bone Marrow |
|
|
Term
| Which ALAS enzyme is negatively regulated by heme? |
|
Definition
|
|
Term
| What regulates ALAS2 synthesis? |
|
Definition
|
|
Term
| What is X-linked Sideroblastic Anemia (XLSA)? |
|
Definition
| A deficiency in ALAS 2 that causes iron accumulation in erythroid cells. |
|
|
Term
| Why does CYP synthesis cause increased heme production in the liver? |
|
Definition
| It uses heme, so ALAS 1 in the liver has its negative regulation removed and is synthesized. |
|
|
Term
| How will iron deficiencies affect ZPP levels? |
|
Definition
|
|
Term
| What does a blood ZPP > 40umol ZPP/ mol heme means? |
|
Definition
| Protophyrin conversion to heme is impaired |
|
|
Term
| How is ZPP used as lead toxicity screen? |
|
Definition
| ZPP is elevated in someone with lead toxicity. |
|
|
Term
| What does δALA dehydratase use as a cofactor, and how can lead poisoning affect this? |
|
Definition
Zinc.
Zinc can be substituted with Lead, making it non-functional. |
|
|
Term
| What is the most sensitive enzyme in heme synthesis? |
|
Definition
|
|
Term
| What inhibits Uroproohyrinogen III Oxidase? |
|
Definition
|
|
Term
| What inhibits Ferrochelatase? |
|
Definition
|
|
Term
| What causes porphyria diseases? |
|
Definition
| Partial deficiency in any heme-synthesis enzyme but δALA Synthase |
|
|
Term
| How does porphyria generally present in patients? |
|
Definition
| As acute neurological complications or photo-sensitive skin problems. |
|
|
Term
| How do precipitating factors cause AIP Porphyria attacks? |
|
Definition
| Decrease heme concentration and increase δALA synthetase, causing porphyrinogen accumulation. |
|
|
Term
| What does the Watson-Shwartz test analyze? |
|
Definition
|
|
Term
| What are the normal urine levels of δALA, PBG, Uroporphyrin, Coproporphyrin, and Protoporphyrin? |
|
Definition
δALA<4000
PBG<3500
Uroporphyrin<80
Coprophyrin<280
Protoporhyrin = None
|
|
|
Term
| Why are women more prone to AIP attacks during menstruation? |
|
Definition
1. progesterone catabolizes heme
2. Estrogen and Progesterone have an inductive effect on δALA synthase expression. |
|
|
Term
What deficiency causes Acute Intermittent Porphyria (AIP)?
|
|
Definition
|
|
Term
| What causes δALA accumulation to have neurological toxicity? |
|
Definition
| δALA is a potent agonist of GABA |
|
|
Term
| What causes Tyrosinemia Type I? |
|
Definition
| Fumarylacetoacetate Hydrolase deficiency |
|
|
Term
| Why does Type I Tyrosinemia cause AIP symptoms? |
|
Definition
| Succinylacetone is created, which inhibits δALA dehydratase |
|
|
Term
| What deficiency causes Porphyria Cutanea Tarda (PCT)? |
|
Definition
| Uroporphyrinogen III decarboxylase |
|
|
Term
| Hexachlorobenzene (HCB) is a poison that affects what enyzme in heme synthesis? |
|
Definition
|
|
Term
| What are the best treatments for Porphyrias? |
|
Definition
Hemin (allosterically inhibits ALAS)
Glucose-rich diets (Glucose in high levels has an inhibitory effect on ALAS) |
|
|
Term
| What is the only action in the body that produces CO? |
|
Definition
| Heme Degredation (biliverdin->bilirubin) |
|
|
Term
| What does bilirubin bind to in the blood? |
|
Definition
| Albumin (one albumin can bind to two bilirubin) |
|
|
Term
| A lack of stercobilin in the stool will lead to what color? |
|
Definition
|
|
Term
| Why can't the kidney secrete unconjugated bilirubin? |
|
Definition
| It's tightly bound to albumin |
|
|
Term
| What is the only type of bilirubin that can enter the brain? |
|
Definition
|
|
Term
| What does unconjugated bilirubin deposits in the brain cause? |
|
Definition
|
|
Term
| What does unconjugated bilirubin deposits in the tissues cause? |
|
Definition
|
|
Term
| How do you test for bilirubin levels? |
|
Definition
Direct (Conjugated): Ehrlich's Reagent
Total: Ehrlich's + Methanol
Indirect (Unconjugated): Total-Direct |
|
|
Term
| Why does the sclera of the eye have a higher affinity for bilirubin? |
|
Definition
| It has a high elastin content |
|
|
Term
| Neonatal Physiological Jaundice is a result of the delayed expression of what enzyme? |
|
Definition
| Bilirubin UDP-glucuronyltransferase |
|
|
Term
| Why does blue light therapy help neonatal physiological jaundice? |
|
Definition
| It induces the conversion of bilirubin into less toxic products that can be excreted in the urine. |
|
|
Term
| What causes nonphysiological unconjugated and conjugated bilirubin levels to rise? |
|
Definition
Unconjugated: 1) overproduction of bili 2) impaired liver uptake of bili 3) reduced conjugation ability of liver
Conjugated: 1) impaired excretion from liver/gallbladder
2) blockage of common bile duct |
|
|
Term
| How do you treat Crigler-Najjer Syndrome II and why? |
|
Definition
| High phenobarbitals to increase bilirubin-UDP-glucuronyltransferase expression |
|
|
Term
| What enzyme is affected in Crigler-Najjar Syndrome I and II? |
|
Definition
| bilirubin-UDP-glucuronyltransferase |
|
|
Term
| What is Gilbert syndrome? |
|
Definition
| A harmless condition resulting in 30-40% bilirubin-UDP-glucuronyltransferase functioning that is treated with phenobarbitals |
|
|
Term
| What is the purpose of MRP2/Multispecific Organic Anion Transporters (MOAT)? |
|
Definition
| Enables conjugated bilirubin to be secreted into the canaliculi |
|
|
Term
| What deficiency causes Dubin-Johnson Syndrome? |
|
Definition
|
|
Term
| What is upregulated as a result of MRP2 deficiencies causing conjugated bilirubin build up? |
|
Definition
|
|
Term
| What are the purines and what are the pyrimadines? |
|
Definition
Purines: GA
Pyrimadines: CUT
|
|
|
Term
| What will a deficiency in thioredoxine cause? |
|
Definition
| Ribonucleotide reductase deficiency |
|
|
Term
| Why do anti-cancer drugs like Hydroxyurea cause ribonucleotide reductase problems? |
|
Definition
| It innactivates free tyrosyl radicals, which it requires |
|
|
Term
| What allosterically inhibits and activates ribonucleotide reductase? |
|
Definition
inhibit: dATP
activate: ATP |
|
|
Term
| Folate Deficiency will affect De Novo synthesis where? |
|
Definition
| The steps that require transformylase, leading to megaloblastic anemia. |
|
|
Term
| How does methotrexate, an anti-cancer drug, affect nucleotide synthesis? |
|
Definition
| It is an inhibitor of DHF reductase, so it prevents the formation of THF and N10-formyl THF |
|
|
Term
| What causes Dihydropyrimidine DH deficiency (DPD) in patients treated with 5-FU? |
|
Definition
| Excessive 5-FdUMP and 5-FUTP |
|
|
Term
| What causes orotic aciduria? |
|
Definition
| UMP synthase deficiency (OMPD and OPRT) |
|
|
Term
| How do you treat orotic aciduria? |
|
Definition
Uridine treatement: creates UMP=>UTP.
UTP blocks CPSII |
|
|
Term
| How do you differentiate if orotic aciduria is caused by urea cycle defect or pyrimidine synthesis defect? |
|
Definition
| Urea cycle orotic aciduria is accompanied by hyperammonemia. |
|
|
Term
| What causes Lesch-Nyhan Syndrome? |
|
Definition
| HGPRT deficiency leading to Uric Acid in blood |
|
|
Term
| At a neutral pH, what does uric acid exist as in the body? |
|
Definition
|
|
Term
| Where does over half the antioxidant capacity of blood plasma come from? |
|
Definition
|
|
Term
| How do Allupurinol and Febuxostat help treat Hyperuricemia and Gout? |
|
Definition
| They both inhibit Xanthine Oxidase, preventing Uric Acid production. |
|
|
Term
|
Definition
| A recombinant UA oxidase that converts UA into allantoin to prevent sodium urate crystals, which can cause ARF. |
|
|
