____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