____undergo pyruvate dehydrogenase kinase (reversible phosphorylation II)
Mammals
Pyruvate dehydrogenase kinase is allosterically
-inactivated by pyruvate
-activated by NADH, Acetyl CoA
The serine residue of E1-PDH phosphorylated blocks
decarboxylation of pyruvate and halts formation of acetyl-CoA
In regulation of pyruvate DH reaction, ______inactivates and _____activates
-phosphorylation
-dephosphorylation
The reactivation of pyruvate dehydrogenase requires_____ in reversible____
-pyruvate dehydrogenase phosphatase
- phosphorylation II
-Allosterically activated by Ca2+(sends strong signal which causes muscle contractions)
- Hydrolyzes the phosphorylated serine in E1
- Remains associated as long as NADH/NAD+ and acetyl-CoA ratios are low
- High concentrations of NADH or Acetyl-coA inactivate the phosphatase and cause it to dissociate from the complex
Pyruvate dehydrogenase
The cascade of reactions stimulated by insulin binding to its receptors which activates pyruvate DH phosphatase which in turn activates pyruvate DH
Hormonal control
When phosphatase is active, the serine of E1 is phosphorylated and converts
pyruvate to acetyl coA
When phosphatase is inactive, the Pi on Ser of E1 does not allow for pyruvate to
convert to acetyl CoA
Pyruvate dehydrogenase phosphatase turns on
+ Ca2+
+ Insulin
Pyruvate dehydrogenase kinase turns on ____ and _____, and turns off ___ and ____.
- Acetyl-CoA and NADH
-Ca2+ and ADP
The 3 reactions that are regulated in the TCA Cycle
-citrate synthase
- isocitrate dehydrogenase
-a-ketoglutarate dehydrogenase
-ATP, NADH, and succinyl-CoA inhibit
-Low energy
citrate synthase
-ATP inhibits, ADP and NAD+ activate
Isocitrate dehydrogenase
-NADH and succinyl-CoA inhibit, AMP activate
-High energy signal
a-ketoglutarate dehydrogenase
In the TCA cycle, NADH inhibits in:
PDHC, citrate synthase, a-KGDHC, Isocitrate DH
In the TCA cycle, Acetyl-CoA inhibits:
PDHC
In TCA cycle, citrate inhibits:
citrate synthase, PFK1
In TCA cycle, succinyl CoA inhibits:
citrate synthase, a-KGDHC
In TCA cycle, ATP inhibits/ADP activates:
isocitrate DH
In the TCA cycle, Ca2+ activates:
Isocitrate DH, PDHC, and a-KGDHC
Calcium signals____ ______ and thus production of ATP for fuel
- muscle contraction
PDHC is regulated by:
-Product inhibition- NADH and Acetyl-CoA
-Covalent modification-(phosphorylation and dephosphorylation of E1)
The proportional rate to oxygen consumption, NADH reoxidation, and ATP productions are
tightly coupled
What do we see due to the TCA cycle?
a connection between sugar metabolism and now- fatty acids, steroids, amino acids, nucleotides and prosthetic group
The TCA cycle has no need for
-Amino acids , cholesterol, fatty acids, and glucose
Can all 20 common amino acids be made from metabolites derived from the TCA cycle
YES
a-ketoglutarate can make
purine nucleotides, Glutamate, Arg, and Pro
Succinyl CoA can be used to make
porphyrins (heme hb)
Fumarate and oxaloacetate can be used to make several
amino acids and pyrimidine nucleotides
These enzymes catalyze reactions that replenish TCA cycle intermediates
Anaplerotic reactions
What are the 3 filling up reactions in the TCA Cycle?
-PEP carboxylase
- Pyruvate carboxylase
- Malic enzyme
How does PEP carboxylase aid in the replenishment of intermediates in TCA cycle?
converts PEP to oxaloacetate
How does pyruvate carboxylase aid in the replenishment of intermediates in TCA cycle?
converts pyruvate to oxaloacetate
How does malic enzyme aid in the replenishment of intermediates in TCA cycle?
coverts pyruvate into malate
The ___ is impermeable to almost everything and has transporters
Inner mitochondrial membrane
Pyruvate carboxylase occurs only in the
mitochondria
Because oxaloacetate cannot be transported across the mitochondrial membrane, it is reduced
to malate
Has 2 routes:
1. Aspartate aminotransferase: doesn't require NAD/NADH
2. Malate dehydrogenase: required NAD/NADH thus reducing equivalents can be transported across the IMM
Malate-Aspartate shuttle

What shuttle is this?
Malate-Aspartate shuttle
What shuttle is this?
Glcerophosphate shuttle
-Electrons from NADH are transferred to FAD via a reaction catalyzed by 3-phosphoglycerol dehydrogenase
1. Ketone converted to OH in reduction as NADH is oxidized
2. OH converted back to ketone as FAD is reduced to FADH2
3. FADH2 part of flavoprotein dehydrogenase that transport 2e to the ETC
Glycerophosphate shuttle
The ____ ______ offers a solution for plants, some bacteria, and algae.
glyoxylate cycle
Since plants can't accomplish efficient photosynthesis, they rely on
acetate as a carbon source
Net-synthesis of carbohydrates and other intermediates from acetate is not possible with TCA cycle
Acetate based growth
What are the short circuiting enzymes?
Isocitrate lyase and malate synthase

Understand cycle and what is this cycle?
Glyoxylate cycle
Excess glucose and acetyl-CoA can easily be converted
into fat
Excess acetyl-CoA and most fatty acids can not support
net glucose synthesis
Plants and some microbes can convert _______ but not humans
acetyl CoA-> gluc