HMP Shunt Pathway Flashcards
What is the overall point of the HMP Shunt Pathway?
Alternate Pathway for Glucose Metabolism
Roles of HMP Shunt Pathway
What Pathway will require 5 carbon Sugars
glycolysis?
glycogen storage
fatty acid synthesis
RNA synthesis
TCA Cycle
RNA synthesis — we can make the 5 carbon sugars needed for RNA (and DNA?)
Oxidative vs. Non-Oxidative Pathways
Transketolase vs. Transaldolase
Transaldolase requires
a lysine in the active site.
Which other enzyme requires thiamin as a cofactor?
Pyruvate kinase
Pyruvate dehydrogenase
Isocitrate dehydrogenase
Aldolase
Aminoacylt tRNA
Alpha KG Dehydrogenase
Pyruvate dehydrogenase
Alpha KG Dehydrogenase
Review of Thiamine Deficiency
The Oxidative Steps of HMP
Epimerization and Isomerization of Ru5P
What other reaction pathway contains a similar Epimerization reaction?
Glycolysis
Fructose Metabolism
Galactose Metabolism
TCA Cycle
Mitochondrial Shunts
Galactose Metabolism — C4 Epimerase
TCA Cycle — Isomerase but not epimerization
First Transketolase Reaction
First TransALDOLASE Reaction
What happens to the E4P produced?
Regulation of the HMP Shunt Pathway
Which pathway requires NADPH?
Glycolysis
Gluconeogenesis
Xenobiotic Detoxification
Fatty Acid oxidation
TCA Cycle
Ox. Phos.
Xenobiotic Detoxification — Cytochrome System requires NADPH
What are the 3 types of Cells?
- Cells require more R5P than NADPH
- Cells that need equal amounts of R5P than NADPH
- Cells require NADPH but not R5P
Cells that require more R5P than NADPH
Cells that Need Equal Amounts of NADPH and R5P
Cells that Require NADPH, but not R5P
Rationale behind the different Pathways
Cells that need NADPH and Carbons for Biosynthesis
Overview of the Metabolism
Summary of Directions of the HMP Pathway
Biochemical Consequences of G6PDH Deficiency
Symptoms of People with G6PDH Deficiency
Soldiers got the following symptoms:
Scleral Icterus
Jaundice
Hemolytic Anemia
Mediterranean descent
Mutation on X-Chromosome that was G6P
They were aysomptomatic until they received drugs at home. Drugs are oxidizing agents which triggered the disorder.
RBC’s are primarily affected. Remember RBC’s have no mitochondria.
THE RBC use transhydrogenase as their only means of generating NADPH
Consequences of G6PDH Deficiency Continued
Glutathione Pathway
G6PDH Deficiency Defined
G6PDH Resistance to Malaria
Sickle Cell Carrier Resistance to Malaria
Overview of Eythrocyte Metabolism
Erythrocyte has pathways that some other cells don’t.
Upper Right Branch of the pathway is dependent on NADP concentration.
Iron atom in center of heme binds oxygen but it can only bind…… not the ferric state.
Methemoglobin gets converted back to the hemoglobin by met reductase.
Whenever we go through the 2,3 BPG shunt we’re by passing the generation of an ATP.
Reactive Oxygen Species
Which organelle would you expect to exhibit the most damage from ROS?
Lysosome
Mitochondria
Golgi Apparatus
Endoplasmic reticulum
Nucleus
Mitochondria
Enzymes which use Molecular Oxygen
Cytochrome P450 Family
More on Cytochrome P450
Tylenol Toxicity
Radical Damage and Chain Terminators
Anti-Oxidant Enzymes
A major role of the HMP shunt pathway is?
Generate ATP
Generate NADH
Generate FADH
Bypass PFK1
Provide cofactor for anabolic pathways
Providing cofactor for catabolic pathways
Provide cofactor for anabolic pathways
Production of glucose from ribose 5-phsophate in the liver would require which one of the following enzymes?
Pyruvate carboxylase
pyruvate dehydrogenase
PEP Carboxykinase
G3P DH
Fructose 1,6 Bisphosphatatse
Fructose 1,6 Bisphosphatatse
Level of oxidative damage is 10 times greater than nuclear DNA Why?
Superoxide dismutase is present in the mitochondria
Nucleus lacks glutathione
Nuclear membrane presents a barrier to ROS
Mitochondrial membrane is permeable to ROS
Mitochondria DNA Lacks Histones
Mitochondria DNA Lacks Histones — So it’s not protected from ROS
G6PDH Deficiency?
Chronic Alcoholic has nystagmus, inability to balance, easily confused. Which enzyme assay would likely demonstrate a reduction of activity?
Alphaketoglutarate dehydrogenase — only enzyme listed that requires Thamine
See Above. Assay of which of the following enzymes can determine a biochemical reason for these symptoms?
Isocitrate DH
Transaldolase
Transketolase
G3PDH
G6pDH
Transketolase
New born gets treated with thiamin to alleviate symptoms of lactic acidosis lethargy and poor muscle tone. Why is the treatment successful?
Such treatment allows the mutated enzyme to produce NADPH
The mutated enzyme has a reduced Km for thiamine
The mutated enzyme has an increased Km for thiamine
Such treatment allows cells to produce 5 carbon sugars which are necessary for cell division
The mutated enzyme has an increased Km for thiamine (I.e. Reduced Affinity)
The conversion of Ribose 5 Phosphate to free glucose in liver requires?
G6PDH
Pyruvate Kinase
Malate Dehydrogenase
Aldolase
G3PDH
Aldolase
American american male had fave beans he was fatigued and shows anemia. What is the likely defect?
NADH
NAD
Reduced Glutathione
Oxidized Glutathione
Cystine
Homocystine
Reduced Glutathione
Glutamic Acid can be converted into alpha KG in one step which enzyme below is required for the alpha ketoglutarated to be covered to free glucose?
Citrate Synthase
PFK1
Pyruvate Kinase
Pyruvate Carboxylase
Aldolase
Aldolase — you need aldolase to make Fructose 1,6 BP
Individual of mediterranean descent develops hemolytic anemia can still generate 5 carbon sugars from glucose requiring the participation of which of the following enzymes below?
G6PDH
G3PDH
PFK1
Pyruvate Kinase
F1,6BP
PFK1
A drug developed to inhibit PEP carboxykinase would not block gluconeogenesis from which substrate?
Aspartate
Lactate
Glutamate
Glycerol
Succinyl CoA
Glycerol
New born exhibits hypoglycemia during periods of fasting. Enzyme assays reveal a defective phoshoglucomutase. This led to reduced glucose production from which on e of the following?
Glycogen
F6P
Glycerol
Lactate
Aspartate
G6P
Glycogen — only one requires phosphoglucomutase
AN individual inherited a mutation in the gen for the UDP Glucose pyrophosphorylase such that it is 95% inactive? This is the consequence of which disorder?
Inability to use either galactose or glycogen as an energy source
Inability to make glycogen from any sugar or to utilize galactose as an energy source.
Inability to make glycogen from any sugar or to utilize galactose as an energy source.
Individual has a mutation of UDPGLucose Epimerase. What is the likely consequence of this disorder?
Inability to use galactose as an energy source with no effect on the ability to use glycogen
