TCA cycle + Mito

Question 1

How permeable is the out mito membrane?

Answer 1

It is permeable to most molecules under 6kDa. The comp. is ~45% cholesterol

Question 2

What is the impermeable inner mito. membrane composed of?

Answer 2

Almost no cholesterol, mostly cardiolipin. This allows gradients to be established

Question 3

What is the [H+] in the inter membrane space and the matrix.?

Answer 3

Intermembrane: [H+] is high
Matrix: [H+] is low

Question 4

What does the mito DNA encode?

Answer 4

Proteins used in the ETC and tRNAs used to translate the proteins.

Question 5

How do into reproduce and how are they inherited?

Answer 5

by fission and inherited maternally

Question 6

What does mtDNA being hypermutatable mean?

Answer 6

mtDNA is naked. Not wound around histones. Also exposed to more ROS than nDNA. ROS damage increases with age. Also the mito. genome has limited ability to repair itself

Question 7

What does mtDNA being heterogenous mean?

Answer 7

There are many copies of mtDNA in the mito and multiple mitos in the cell. Also because of this diseases in the mito are heterogenous meaning both normal and mutants can exist. Also they tend to get worse with age.

Question 8

Since glycolysis is in the cytosol and the TCA cycle is in the mito, where does the shift happen?

Answer 8

Pyruvate is transported into the mitochondria where PDH converts it to acetyl CoA.

Question 9

What transfers pyruvate into the mito?

Answer 9

MPC (mito. pyruvate carrier) acts as a heterodimer of two subunits: MPC1 (BRP44L) and MPC2 (BRP44)

Question 10

What do inherited mutations in MPC1 cause?

Answer 10

Lactic acidosis and hyperpyruvatemia

Question 11

How is PDH regulated?

Answer 11

By phosphorylation (inhibit) and dephospho-rylation (activate). PDK1-4 (2 is common) exist and is active when energy levels are high, starvation or deprivation, and low O2. PDP1 is activated by Ca++ which activates PDP2. Arsinate and organic arsenical permanently inhibit PDH

Question 12

What are different sources of acetyl CoA?

Answer 12

FAs, ketone bodies, glucose, pyruvate (by alanine), ethanol

Question 13

What is the rate limiting in the TCA cycle?

Answer 13

Isocitrate deydrogenase. Converting Isocitrate to alpha-ketoglutarate.

Question 14

What two reactions in the TCA cycle have a + delta G?

Answer 14

Malate to Oxaloacetate by Malate dehydrogenase and citrate to isocitrate by aconitase.

Question 15

What forms citrate from oxaloacetate and acetyl CoA?

Answer 15

citrate synthase

Question 16

What reaction does aconitase catalyze and substrates?

Answer 16

Citrate to aconitate to isocitrate using and giving off water in an isomerization rxn.

Question 17

What catalyzes isocitrate to alpha-ketoglutarate?

Answer 17

IDH3 making NADH giving off CO2. Decarboxylation makes NADH or FADH2. uses TPP

Question 18

what catalyzes alpha-ketoglutarate to succinyl CoA?

Answer 18

alpha-ketoglutarate dehydrogenase. Another decarboxylation making NADH and CO2.

Question 19

How many enzymes are in alpha-ketoglutarate dehydrogenase and what do they catalyze?

Answer 19

E1: decarboxylase TPP
E2: transacylase lipoate
E3: dihydrolipoyl dehydrogenase FAD

Question 20

What does Succinate Thiokinase catalyze?

Answer 20

Succinyl CoA to Succinate making GTP giving off CoASH. Strongly exergonic run coupled to GTP syn.

Question 21

What does SDH catalyze?

Answer 21

Succinate to Fumarate. Also complex II of the ETC. The FADH2 generated goes directly to the ETC through the enzyme. Also is a tumor suppressor?

Question 22

What catalyzes fumarate to malate?

Answer 22

Fumarate Hydratase or fumarase. Hydratases add water to a double bond.

Question 23

What catalyzes malate to oxaloacetate?

Answer 23

Malate dehydrogenase reducing NAD+ in the process

Question 24

How many ATP does the TCA cycle produce and what makes it up?

Answer 24

10ATP. 3NADH, 1FADH2, 1GTP

Question 25

If NADH/NAD+ ratio increases what happens to oxaloacetate and isocitrate?

Answer 25

Oxaloacetate decreases in amount because NADH is product of its formation, Isocitrate increases in amount because NADH is made in its conversion

Question 26

Is the TCA cycle catabolic or anabolic?

Answer 26

BOTH reduces NAD+ and FAD for gen. of ATP through ETC but also the intermediates are feedstock for other biosynthetic pathways.

Question 27

What does citrate feed?

Answer 27

FA biosyn

Question 28

What doess oxaloacetate feed?

Answer 28

A.A. biosyn.

Question 29

What does Malate feed?

Answer 29

gluconeogenesis

Question 30

What does Alpha-ketoglutarate feed?

Answer 30

glutamate then to GABA

Question 31

What does Succinyl CoA feed?

Answer 31

Heme biosyn.

Question 32

What does pyruvate carboxylase do and why?

Answer 32

Converts pyruvate to oxaloacetate by adding HCO3- using biotin

Question 33

What a.a.s make pyruvate and eventually oxaloacetate?

Answer 33

Alanine and serine

Question 34

What is the difference between glutamate and alpha-ketoglutarate?

Answer 34

glutamate has an extra amine

Question 35

What is the pathway that converts ADP to fumarate?

Answer 35

2ADP to ATP and AMP by adeylate kinase. AMP to IMP by AMP deaminase. IMP + aspartate + GTP to adenylosuccinate by synthetase. Adenylsuccinate to fumarate by adenylsuccinase.

Question 36

What is Myoadenylate deaminase deficiency?

Answer 36

An inherited mutation of the gene coding AMP deaminase 1 and it becomes inactive. Get muscle pain and weakness when exercising. There is no NH4+ in blood after exercising. No AMPD1 in muscle biopsy.