TCA cycle (final exam)

Define cellular respiration

-a process in which cells consume O2 and produce CO2

-provides a lot ATP

-oxygen ultimately reduced to water

-lots of e- pulled out (extracts lots of energy)

Where does the citric acid cycle occur in eurkaryotes?

the mitochondria

Where is pyruvate made?

made in the cytosol by glycolysis

Which enzyme is responsible for turning pyruvate into Acetyl-CoA?

pyruvate dehydrogenase complex

-gives off CO2 as well as by product

Which enzyme converts acetyl-CoA into citrate and what by product is formed?

enzyme Citrate synthase

-by product CoA-SH

Which enzyme converts citrate into Isocitrate?

-Enzyme aconitase thru intermediate form cis-Aconitate

Which enzyme oxidizes Isocitrate to a-ketoglutarate and what are 2 byproducts?

enzyme isocitrate Dehydrogenase

-byproduct CO2 and NADH + H+ OR NADPH + H+

Which enzyme oxidizes a-ketoglutarate to succinyl-CoA and what are 2 byproducts?

-Enzyme a-ketoglutarate dehydrogenase complex

-byproducts CO2 and NADH + H+

Which enzyme converts succinyl-CoA into succinate and what are 2 byproducts?

-enzyme succinyl-CoA synthetase

-byproduct GTP or ATP bc it uses GDP/ATP in this step

-byproduct CoA-SH

Which enzyme oxidizes succinate to fumarate and what is the product?

-enzyme succinate dehydrogenase

-byproduct FADH2

How many hydrogens can FAD accept?

1 or 2

Name the only integral membrane protein in the TCA cycle

Succinate dehydrogenase

Which enzyme converts fumarate to malate?

-enzyme fumarase; uses carbanion transition state

Which enzyme oxidizes malate to oxaloacetate and what is the byproduct?

-enzyme malate dehydrogenase

-byproduct NADH + H+

How many ATP molecules are produced from the electrons of NADH?

2.5 ATP

How many ATP molecules are produced from the electrons of FADH2?

1.5 ATP

What 3 factors control flux through the TCA cycle?

-substrate availability

-inhibition by the accumulation of products

-allosteric feedback inhibition of early steps

What are the 4 regulations of the TCA?

-the conversion of pyruvate to acetyl-CoA (the pyruvate dehydrogenase complex).

–The entry of acetyl-CoA into the cycle (citrate synthase).

– Isocitrate dehydrogenase.

– α-ketoglutarate dehydrogenase.

The TCA cycle pulls large amounts of electricity from carbon molecules and produces how many NADH, FADH2, ATP/GTP, and CO2 per 1 acetyl-CoA?

Per 1 Acetyl-CoA or per turn

-3 NADH

-1 FADH2

-1 ATP or GTP

-2 CO2

The TCA cycle pulls large amounts of electricity from carbon molecules and produces how many NADH, FADH2, ATP/GTP, and CO2 per glucose molecule?

1 glucose —> 2 acetyl Co-A

-6 NADH

-2 FADH2

-2 ATP/GTP

-4 CO2

Oxidative phosphorylation

-includes the ETC and ATP synthase

-purpose: uses NADH and FADH2 to generate large amounts of ATP

Where does the electron transport chain occur in?

The inner mitochondrial membrane

The outer mitochondrial membrane is blank while the inner mitochondrial membrane is blank

-permeable

-impermeable

How does pyruvate enter the inner mitochondrial membrane?

Enters thru a pyruvate-proton symporter. It uses the proton concentration gradient to cotransport pyruvate into the mitochondrial matrix, making it a form of secondary active transport.

-chemical gradient = difference in concentration,

Explain the steps of the Pyruvate Dehydrogenase Complex (pyruvate —> acetyl-CoA)

Step 1

TPP attacks pyruvate

Step 2

CO₂ is released

Step 3

Acetyl group transferred to lipoamide arm

Step 4

Acetyl group transferred to CoA

Makes:

Acetyl-CoA

Step 5

Lipoamide arm becomes reduced

Step 6

FAD reoxidizes lipoamide

Produces:

• FADH₂

Step 7

NAD⁺ oxidizes FADH₂

Produces:

• NADH + H⁺

CoA (PDH)

-Acyl carrier

-contains thiol group (-SH)

-forms thioester linkage

-business end of CoA

Thiamine Pyrophosphate (PDH)

-derived from VitB1

-creates carbanion

-lightsaber of nucleophiles

-attacks pyruvate

Lipoic Acid

-lysine residue

-acts like an arm

-moves intermediates between active sites

Define Anaplerotic Reactions

Reactions that replenish citric acid cycle intermediates

-stuff can come out but stuff can also go in

-maintains homeostasis and keeps cycling running

What can inhibit the PDH?

-ATP

-NADH

-Acetyl-CoA

-Fatty acids

-there’s already enough energy, why make more?

What can activate the PDH?

-AMP

-CoA

-NAD+

-Calcium

Hormonal Regulation of PDH: Glucagon

-in liver

-means “im hungry”

-glucagon binds to GPCR —> PKA

-PKA phosphorylates

-PDH off

-liver should release glucose, not burn it

Hormonal Regulation of PDH: Insulin

-insulin means “fed state”

-insulin binds to RTK —> PKB

-PKB dephosphorylates

-PDH is ON

-Reason: store incoming calories as fat

Hormonal Regulation of PDH: Epinephrine

-In muscle lots of ATP needed

-Epinephrine binds to GPCR —> PKA

-PKA phosphorylates

-PDH On

-Reason: muscles need energy immediately