PPP, PDH Comples, TCA Flashcards
Where does PPP occur
Cytoplasm
What is the first thing to do when glucose gets to a cell
PPP
Substrate for PPP
G6P
Main role of PPP
Produce NADPH
Second main role of PPP
Make ribose 5 phosphate for nucleotide synthesis
What is NADPH used for
Synthesis of molecules
Production of fat
Protection against ROS
Detoxify xenobiotics
First step of PPP is
Irreversible
What are the two phases of PPP
Oxidative (making)
irreversible
Nonoxidative (making)
reversible
What are key enzymes in oxidative path of PPP
Glucose 6 phosphate dehydrogenase!!!!! Very important
6 phosphogluconate dehydrogenase
What are the 2 important products of oxidative PPP
NADPH - used for anabolism
5 carbon sugar - ribulose 5 phosphate - used for DNA/RNA synthesis
What’s the most common genetic disease in the world
G6PDH deficiency
What part of PPP is thiamine dependent
Non-oxidative transketolase (C2 unit)
Beri beri
2 important parts of non-oxidative PPP
Transketolase C2 unit
Transaldolase C3 unit
Non-oxidative involves
Carbohydrates with different number of carbons
How does PPP connect to glycolysis
Via F6P or glyceraldehyde 3 phosphate
How do you regulate PPP
NADPH!
It inhibits G6PD
The liver G6PD is ______ enzyme by _____
Inducible
Insulin
What kind of eating would favor PPP
a high insulin/glucagon ratio
high carb meal
How is the PPP self regulated
By looping back to glycolysis
G6PDH deficiency is x-linked recessive which means
It’s more prevalent in males
G6PDH deficiency is _____ induced by _____
Hemolysis
Oxidative stresses
How does pyruvate get from cytoplasm to mitochondria
2 step process
1: cross mitochondria outer mem thru voltage-dependent anions channel (VDAC) with Pi
2: then its moved to the matrix through pyruvate symporter with a proton
energy consuming step
Which step in getting pyruvate from cytoplasm to mito is energy consuming
To the matrix with a proton
Where does PDH happen
Mitochondria
What does PDH do
Turns pyruvate to acetyl CoA
When does PDH happen
When you have a low ATP/ADP
And enough oxygen
What are the 5 cofactors of PDH
Tender loving care for Nancy
T = thiamine (B1) pyrophosphate
L = lipoid acid
C = CoA (B5)
F = FAD (B2)
N = NAD+ (B3)
5 enzymes of PDH
E1
E2
E3
PDH kinase
PDH Phosphatase
E1 of PDH function
Assist in attaching acetyl group of pyruvate to TPP and releasing CO2
E2 of PDH function
Transfers acetyl group from TPP to lipamide 1 and then lipamide 2
Moves the acetyl group, to CoA to make acetyl CoA
E3 of PDH function
Reoxidized the lipoamide, this is necessary for the process to continue
Write the PDH reaction
Pyruvate + CoA + NAD
=
acetyl CoA + NADH + CO2
Steps catalyzed with E1
Decarboxylation of pyruvate oxidation of product
Steps catalyzed E2
Transfer of acetyl group to coenzyme A
Steps catalyzed E3
Transfer of electrons to NAD+
Coenzyme A components
Pantothenic acid (B5)
3’5’ AMP
-SH group
Acetyl CoA - acetyl replaces the H on SH to form acetyl CoA
What is the first level of regulating PDH
Substrate activation and product inhibition
What are activators of PDH activity
Pyruvate, CoASH and NAD
What are inhibitors of PDH
Acetyl CoA and NADH
What is the second level in regulating PDH
Covalent modification
Second level of PDH reg inhibitors
Phosphorylation by PDH kinase
Second level of PDH reg activation
Dephosphorylation by PDH Phosphatase
What does NOT reg PDH activity
Glucagon and insulin
What are activators PDH process that are allosteric
What are they activating
What are they a saying
NADH
Acetyl CoA
PDH kinase
We have enough energy, slow down
What are activators of PDH phosphatase
Mg2+
Ca2+
What are inhibitors PDH kinase and what are they all
allosteric regulation
CoA
ADP
Pyruvate
NAD+
PDH deficiency symptoms
Increased pyruvate
Increased lactate
Increased alanine
=chronic lactic acidosis
SEVERE NEUROLOGICAL DEFECTS which eventually lead to DEATH
How do you fix PDH deficiency
A diet with reduced carbohydrates
an inhibitor of PDH kinase called, Dicholoroacetate
Primary thiamine deficiency =
Limited thiamine intake
Secondary thiamine deficiency
Alcoholism with reduced
thiamine ingestion
thiamine absorption
Arsenic toxicity on PDH
Inhibits lipoid acid-PDH interaction
Inhibits ATP synthesis
Symptoms = weak, lethargic, nausea, vomiting, TRAVERSE LINE in finger nails
E1 is
α-ketoglutarate dehydrogenase
B1 is a cofactor for _____
Pyruvate dehydrogenase - in glycolysis
Alpha-ketoglutarate dehydrogenase - in TCA
Transketolase - in PPP
Branched chain AA dehydrogenase in - AA catabolism
End product of TCA
Water
2CO2
Release energy
ETC aka
Oxidative phosphorylation
TCA generates _ NADH and _ FADH2 for ____
3
1
ETC/oxidative phosphorylation
___ GTP is made in TCA by ___
1
Substrate level phosphorylation
TCA is ____ dependent
O2 dependent
Everyone but RBC depend on
TCA
TCA is why we need to
Breathe and exhale
7/8 enzymes of TCA are located _____ the 1/8 is ____ and its called _______
Mito matrix
In the inner membrane
Succinate dehydrogenase - its a member of ETC
TCA mnemonic
Can I Keep Selling Sex for Money Officer
C = citrate
I = isocitrate
K = α - ketogluterate
S = succinyl CoA
S = succinate
F = fumarate
M = maleate
O = oxaloacetate
_____ level of NADH inhibit TCA by inhibiting
High
Citrate synthase
Isocitrate dehydrogenase
α - ketoglutarate dehydorgenase
High concentration of citrate tells TCA
Inhibit citrate synthase
____ concentration of calcium tells TCA
High
Activates α-ketogluturate dehydrogenase
What are regulated in parallel
TCA and PDH
What is overal inhibiting to TCA
High ATP and succinyl-CoA
What is overall activating TCA
High ADP
High ca2+
Anaplerosis is
Synthesizing and replenishing the intermediates of TCA
Cataplerosis is
Intermediates escaping from TCA and making other molecules
TCA is mainly regulated by ____ needs. Specifically
Energy
NADH/NAD ratio
ATP/ADP ratio
TCA is very _____ and irreversible or reversible
Dynamic and reversible
