class 10

pyruvate dehydrogenase

under normal conditions, where does pyruvate need to enter

mitochondria

pyruvate → acetyl CoA → further oxidation happens in the presence of

oxygen

glycolysis occurs where

cytosol of cells

normal metabolism of pyruvate occurs where 

mitochondrial matrix

the mitochondrial matrix is ________ to most molecules

impermeable

the pyruvate transporter is a symport or antiport? Why?

symport because it simultaneously transports pyruvate and H+ into the matrix

what allows the transport of pyruvate 

the flow of H+ against a concentration gradient 

what does it mean to be a secondary active transport and give me an example

to be powered by another ion’s gradient, like the H+ ions flowing against their gradient and the Na+ gradient, rather than ATP directly

what part of the membrane is permeable to almost anything from the cytosol

outer membrane

what part of the mitochondria is really impermeable

inner membrane

what part of the mitochondria contains the pyruvate dehydrogenase complex

matrix

the pyruvate transport is a symport or antiport

symport, moves pyruvate and protons

the PDH complex uses pyruvate to yield what?

Acetyl-CoA

which part of the mitochondria contains: respiratory electron carriers, ADP-ATP translocase, ATP synthase, and other membrane transporters

inner membrane

what part of the mitochondria contains: pyruvate dehydrogenase complex, citric acid cycle enzymes, fatty acid beta oxidation enzymes, amino acid oxidation enzymes, DNA, ribosomes, ATP, ADP, Pi, Mg2+, Ca2+, and K+

matrix

When the PDH forms acetyl CoA, what does it release and what does it produce

releases CO2 and NADH and H+ are byproducts

what catalyzes the formation of acetyl CoA from pyruvate

pyruvate dehydrogenase complex (E1 + E2 + E3)

non-protein, organic co-factor that tightly binds with a protein

prosthetic groups

what happens when prosthetic groups are involved with reactions with enzymes

they are involved in the reaction but do not leave the enzyme

what are the 3 prosthetic groups in the PDH complex?

1. FAD

2. TPP

3. lipoic acid

E1 is called:

pyruvate dehydrogenase

E2 is called:

dihydrolipoyl transacetylase

E3 is called:

dihydrolipoyl dehydrogenase

what happens in E1?

CO2 is removed from pyruvate and the remaining 2-carbon fragment is attached to TPP. The thiazolium ring is an active part of TPP which enables decarboxylation by stabilizing, and holding the hydroxyethyl group until it goes to E2. The taking of acetyl after CO2 is removed makes a hydroxyl group.

what does TPP do

takes the acetyl after CO2 has been removed

E1, E2, and E3 all take place where

mitochondrial matrix

what are the cofactors in E1

TPP

what happens in E2

it accepts the 2 carbon (hydroxyethyl group) from E1 onto its lipoamide arm (lipoyllysine), which has 2 sulfurs. It oxidizes it to to an acetyl group, the lipoamide becomes reduced, and transfers it to CoA, forming acetyl CoA. This step is where acetyl CoA is actually produced

what are the cofactors in E2

lipoic acid, and CoA

what happens in E3

The lipoamide in E2 is in its reduced form, and needs to be  reoxidized. It transfers electrons from the reduced lipoamide to FAD → FADH → NAD+ producing NADH + H+. This step regenerates cofactors and captures high energy electrons as NADH. The reduced lipoyllysine rebridges the sulfurs to generate FAD to go to NADH

when do the two sulfurs break and join back together in the PDH complex

The two sulfurs break their disulfide bond during acetyl transfer from E1 to E2, the two sulfurs rejoin (disulfide bond reforms) during the E3-catalyzed reoxidation step, after the acetyl group has left for CoA, regenerating the lipoyllysine for the next reaction cycle.

what does Acetyl CoA go through all the processes to eventually make

ATP

FAD has what kind of group, and which E complex is it associated with

riboflavin (vitamin B2), E3

lipoamide is associated with what E complex, and what amino acid

E2, and lysine

TPP is associated with what E complex, and what vitamin

E1, thiamine (vitamin B1)

what is the reactive site in complex E1

the C2 carbon of the thiazolium ring

what is the reactive site of CoA

the terminal thiol SH group (generates thioester bond with carboxylic acid)

which vitamin is associated with CoA

pantothenic acid B5

components of CoA

beta-mercaptoethylamine, pantothenic acid, 3’-P-ADP

why is the PDH complex a complex

acts as an assembly line, does not rely on distant enzymes

why is the PDH complex fast

it is all in one location

once we get pyruvate, how soon does it want to be used

very quickly

Arsenic and Mercury poisoning goes after which complex, what does it target

E2, lipoyllysine (sulfhydryl groups)

in minerals in mines, and associated with leukemia

arsenic

in thermometers and used to soften hats (made people go crazy)

mercury

what does arsenic and mercury poisoning lead to

CNS disorders and exhaustion