MISC Pathways Flashcards
If you have high insulin, would you expect more or less txn of PEPCK?
Less
remember PEPCK is used to convert Oxaloacetate to pyruvate
Location, location, location
Glycogenolysis: HMP Shunt (PPP): Glycolysis: Gluconeogenesis: TCA:
Glycogenolysis: liver, muscle
HMP Shunt (PPP): cytoplasm
Glycolysis: cytoplasm
Gluconeogenesis: cytosol in liver (80%), kidney (20%)
- exception: pyruvate carboxylase is in mito matrix
TCA: mito matrix
Location, location, location
Triacylglycerol synthesis:
TAG degradation:
Ketogenesis:
Cholesterol synth:
Triacylglycerol synthesis: cytosol
TAG degradation: mitochondria
Ketogenesis: mitochondria
Cholesterol synth: cytosol
(just think: fat synth is in the cytosol)
When do you utilize the HMP pathway?
When glucose is super duper abundant (more than glycogenesis can handle)
2 main fxn of HMP pathway
- generation of NADPH
2. generation of 5C sugars (for nucleotide synth)
tissues/organs where FA + steroid synthesis is common
- mammary gland
- adrenal cortex
- liver
- adipose tissue
- blood forming cells/tumors
NADPH is an E source for?
- FA synthesis
- cholesterol synthesis
- defense against oxidative stress
- White cell fxn
GLycolysis is the major source of E for ?
RBCs
Sperm
Tissues
(Via substrate level phosphorylation)
Counter regulatory hormones
(4)
- What do they respond to?
- glucacon
- catecholamines
- growth hormone
- cortisol
(they are the opposite of insulin, they increase in response to hypoglycemia + stress)
How do CRH like glucagon and catecholamines work?
- Bind to memb. assoc. R
- Change levels of cAMP
- Alter intracellular signaling
- Changel levels of protein kinases
- Phosphorylates key enzymes
Following a meal, glycolysis is (pick one) active/inactive, and glycogen synthase is active/inactive
Active, active
gluconeogenesis and glycogenolysis is reduced
When fasting insulin is ___ and CRH are ___. Gluconeogenesisis is ___, and and glycogen breakdown is ____ to provide glucose for the brain.
insulin - low
CRH - high
Gluconeogenesis - high
Glycogen breakdown - high
If O2 si not present b.c of hypoxia, intense exercise, or the cell does not have mitochondria (RBC), what pathway does the cell take?
Pyruvate gets converted to lactate and exported
When fasting, which organs produce glucose? Where does the liver get its C source?
liver
(kidney to lesser extent 20%)
- Lactate from glycolysis in m. or RBC
- aa from prot. breakdown in m.
- Glycerol from TG breakdown in adipose tissue
ALL GET TRANSPORTED THROUGH THE BLOOD TO THE LIVER AND CONVERTED TO GLUCOSE (GLUCONEOGENESIS)
If a rxn has a low Km, it suggests that substrates have a ______ affinity for the enzyme
strong affinity
-Remember Km is half max, so lower Km = gets to half max faster and rxn will go @ lower substrate [ ]
Why would glycolysis stop if NAD+ is not regenerated? What instance would this occur?
Glyceraldehyde 3 Phosphate would not be oxidized.
- its the first step that requires 2NAD+ to gen 2 NADH when making 1,3 BPG
(low O2, no mito, active skel m, lower blood flow, shock)
Hexokinase vs Glucokinase - selectivity - present in which cells - Km for glucose - Inhibited by?
Hexokinase
- not very selective
- present in all cells
- low Km
- inhibited by G6P
GLucokinase
- selective for glucose
- livr, pancreatic B cells
- high Km
- inhibited by F6P
Both convert Glucose to G6P
If you have higher E, PFK-1 has _____ activity.
lower
PFK-1 converts F6P –> F1,6BP
Most potent activator of PFK1
F2,6,BP
Falling glucose causes Glucagon levels to _____
GLucagon is a CRH that gives you increased glucose output
Phosphorylation of PFK-2 on the PFK-2/FBP-2 complex makes PFK-2 active or inactive?
Does that have a positive or negative feedback on Fructose bisphosphatase-1, which converts F1,6BP to F6P?
Example of CRH that causes phosphorylation.
Phosphorylation makes PFK-2 INACTIVE and FBP-2 ACTIVE
- this impedes formation of F2,6BP
F2,6BP has a negative feedback on Fructose bisphosphatase-1, so IMPEDING F2,6BP allows for FBPase-1 to be active
Example: Glucagon (which activates cAMP –> PKA –> phosphorylates PFK-2/FBP-2
De-Phosphorylation of PFK-2 on the PFK-2/FBP-2 complex makes it active or inactive?
Does that have a positive or negative feedback on PFK-1, which converts F6P to F1,6BP?
Example of CRH that causes phosphorylation.
DeP PFK-2 active and FBP-2 inactive
- this favors formation of F2,6BP
F2,6BP has a Positive feedback on PFK-1
(break down F6P to F1,6BP!)
Insulin
Decreased PKA activity leads to ____ production of F1,6BP?
Increased
remember PKA phosphorylates PFK-2 on the PFK-2/FBP-2, which makes it inactive, which has a neg effect on PFK-1
In starvation state, glucagon levels ___, and cAMP dependent PKA is _____. This leads to activity of the enzyme _____.
increase
activated
FBPase-1
- which converts F1,6BP –> F6P
_____ enzyme deficiency is the 2nd most cause of enzyme deficiency linked hemolytic anemia after ________ deficiency
Pyruvate kinase deficiency
Glucose 6 phosphate dehydrogenase deficiency
Glucagon often results on (pick one) phosphorylation/ dephosphorylation of enzymes.
Phos.
this can either increase or decrease activ. of enzyme dep
Pyruvate dehydrogenase complex is active when it is (pick one) physphorylated / dephosphorylated.
Activated Pyruvate dehydrogenase complex does what?
dephosphorylated
- convert pyruvate–> acetyl CoA
(it is dephosphorylated when insulin is high, with high ADP)
Does pyruvate activate/inhibit the protein kinase which phosphorylates the Pyruvate dehydrogenase complex?
Pyruvate Inhibits Protein kinase
- bc protein kinase inactivates the enzyme that converts pyruvate to acetyle CoA
pyruvate dehydrogenase
Does ATP, Acetyl CoA, and NADH activate or inhibit the protein kinase which phosphorylates the Pyruvate dehydrogenase complex?
They activate protein kinase
All of these want to inactivate PDH because they no longer want pyruvate to be converted to make these substrates.
In the fed state, PDH is _____. IN the fasting state, PDH is _____.
Active (de P)
- wants to convert pyruvate –> acetyl coA
Inactive (P)
- wants to prevent pyruvate conversion
Which is a cofactor for PDH?
Niacin, NAD
During fasting, in the LIVER, gluconeogenic precursors are converted to MALATE, which leaves the ____ to enter gluconeogenesis pathway in the _____
Mitochondria
Cytosol
How does Carbon monoxide poisoning affect the pathways?
Inability of ETC to run even while pO2 remains high bc Hb cannot release O2.
- No energy –> weak –> die
Low ADP (pick one) Increases/ Decreases the flow of e-, which Increases/ Decreases O2 consumption
Decreases, Decreases
ADP and ATP levels are sorta opposite, low ADP = high ATP
Low ATP (Increases/ Decreases) the flow of e-, which (Increases/ Decreases) O2 consumption
Increases, Increases
4 important enzymes that bypass irrev. steps of glycolysis
- pyruvate carboxylase
- PEPCK
- F1,6 BPase
- G6Pase
Why cant Glycogen in skeletal m. be released as glucose? How does it get around this?
Because it lacks Glucose-6-phosphatase
Glucose must be metabolized to lactate via glycolysis in the muscle –>
leave the muscle –>
diffuse into bloodstream and enter liver –>
lactate gets synthesized into glucose via gluconeogenesis –>
provide glucose for brain
What does Biotin do? What does Biotin deficiency lead to___?
Biotin is covalently bound to pyruvate carboxylase, and is needed for CO2 to bind to.
Once CO2 is bound to biotin and activated, it is transferred by pyruvate carboxylase to PYRUVATE to make OXALOACETATE.
if Biotin is deficient, pyruvate builds up –> lactic acid –> lactic acidosis
1st regulated step in gluconeogenesis involves which enzyme?
pyruvate carboxylase
