fates for pyruvate (4)
(1) TCA
(2) lactate
(3) oxaloacetate
(4) alanine
Energy Bookkeeping:
Glycolysis
2 NADH
2 ATP
Energy Bookkeeping:
pyruvate DH
2 NADH
Energy Bookkeeping:
TCA cycle
I cycle:
3 NADH
1 FADH2
1 GTP
each NADH yields ____ ATP
2.5
Each FADH yields ___ ATP
1.5
How many ATP is produced in the end of aerobic
32/38
If NADH from cytosolic glycolysis is transported via the glycerol-phosphate shuttle then only _____ ATP is produced
30/36
Metabolic node
TCA cycle
pyruvate is transported into the
mitochondria
where does oxidative metabolism take place w/in mito?
matrix
pytuvate DH rxn is an
irreversible process
Pyruvate is made into acetyl-coA with what enzyme and cofactor and what is the product
the rxn is catalyzed by pyruvate DH with NAD+ as a cofactor
- CO2 is released
What is so special of CoA?
the sulfur bond
Overall Rxn of the pyruvate DH rxn.
[Pyruvate] + [HSCoA ]+ [NAD+]—-> [AcCoA] + [CO2] + [NADH] + [H+]
coenzyme on E1 of pyruvate DH
Thiamine Pyrophsophate
Thiamine is derived from
Vit. B
thiamine binds to pyruvate on
thiazole ring
E1 releases
CO2
obtained from enriched cereals, grains, pork, legumes, seed, nuts
Vit. B
Deficiency of thiamine leads to
- wernicke’s
- wet beri
- dry beri
wet beri
cardiovascular
dry beri
muscle weakness
A young adult is seen with symptoms of fatigue and muscle cramps. The patient is diagnosed to have a thiamine deficiency. Which of the following metabolic acids is the most likely to accumulate under these circumstances?
A. Oxaloacetate B. Succinate C. Isocitrate D. Malate E. Pyruvate
E. Pyruvate
active arm on E2 of pyruvate DH
lipoate
riboflavin is derived from
Vit. B2
coenzyme on E3 of pyruvate DH
FAD
FAD
accepts electrons from lipoate onto flavin ring
riboflavin deficiency leads to
Chielosis and Glossitis
Pyruvate DH is inhibited by
Phosphorylation
factors that promote dephosphorylation of PDH
insulin and calcium
PDHA1, x-linked
lactic acidosis
PDHA1 tx.
- cofactor (B1/lipoic acid) supplementation
- ketogenic dieat
- bicarbonate/sodium citrate
- dichloroacetate that reduces phosphorylation of PDH
Which two enzymatic steps in the TCA cycle result in production of CO2 through oxidative decarboxylation?
A. Aconitase and pyruvate dehydrogenase
B. Citrate synthase and isocitrate dehydrogenase
C. Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase
D. Pyruvate dehydrogenase and succinyl-CoA synthetase
E. Succinate dehydrogenase and malate dehydrogenase
C. Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase
glutamine can enter the TCA cycle through
alpha-ketoglutarate
speterospecifity enzyme in the TCA cycle
aconitase
alpha-ketoglutarate DH is sensitive to ____ because it has the same coenzymes as PDH
arsenic
citrate inhibits
PFK1
An increase in which of the following ratios causes an increase in the activity of regulated enzymes of the TCA cycle?
A. acetylCoA/pyruvate B. ATP/ADP C. NAD+/NADH D. NADP+/NADPH E. pyruvate/lactate
C. NAD+/NADH
mutations associated with a variety of tumros
isocitrate DH
mutations that cause a predisposition to cutaneous and uterine leiomyomas as well as kidney cancers
Fumarase
mutations associated with phaeochromocytoma
succinate DH
Pantothenic B5
burning feet syndrome
Pyridoxine B6
stomatitis, chielitis, irritability
Biotin
Seborrhea
lipoamide
Dihydrolipoamide DH mutations
who cannot cross the mitochondrial membrane
- OAA
- Acetyl-CoA
PDC has ____ subunits and ____ coenzymes
PDC has 3 subunits and 5 coenzymes
trivalent arsenic poisoning targets
lipoate
Hydroxyethyl-TPP reacts with
lipoate on E2
hydroxyethyl becomes acetyl to form ________ & other S is reduced to _____
hydroxyethyl becomes acetyl to form thioester & other S is reduced to S-H
CoA-SH attacks _____ and takes Acetyl to form _______
CoA-SH attacks thioester and takes Acetyl to form Acetyl-CoA
E3 of PDC helps to regenerate _______ on Lipoate of E2
disulfide bond
FAD has a _____ molecule and it is derived from ________
FAD has a flavin molecule and it is derived from Vitamin B2 (riboflavin)
Vitamin B2 deficiency gives rise to
Glossitis and chielosis
pyruvate DH is inhibited by ________ and ________
phosphorylation and product inhibition
PDC is activated by kinase which is inhibited by _____ and ______ and activated by _______
PDC is activated by kinase which is inhibited by substrates and ADP and activated by products
PDC deficinecy tx. (3)
(1) high fat/low carb-ketogenic
(2) carnitine supplements
(3) NaCO3- helps with Lactic Acidosis
Produce reduced coenzymes: M.I.A
- malate DH: NADH
- isocitrate DH: NADH/CO2
- alpha-ketoglutarate DH: NADH/CO2
succinate DH produces
FADH2
synthase/synthetase makes
CoA
Succinyl-CoA synthetase has substrate level phosphorylation to make
GTP
intestinal epithelium uses _____ as primary fuel source
glutamate
can be converted to aspartate/asparagine
OAA
used in heme synthesis
succinyl-CoA
used to convert to Glutamate/glutamine
alpha-ketogluturate
used to make FAs and Sterols
Citrate
Converted to Pyruvate
Malate
glutamate can be used for
purines
OOA can be converted to _____ then to ______
To PEP and the nto Glucose
aspartate/asparagine used for
purines/ pyrimidines
TCA enzymes are
optically active
alpha-ketoglutarate DH is sensitive to
trivalent arsenis poisoning
______ can pass mitochondrial barrier, thus can cross to ______ to inhibit _____ and inhibit _________ creation
Citrate can pass mitochondrial barrier, thus can cross to cytoplasm to inhibit PFK1 and inhibit Acetyl-CoA
anaplerotic pathway increases the ____ of the TCA cycle
Rate
succinate DH linked to
endocrine tumors
fumarase mut. cause predisposition to
cutaneous/uterine leiomyomas and kidney cancer