BC 27 PDC & TCA

Question 1

PDHC function

Answer 1

decarboxylation of pyruvate for the creation of acetyl coA as a substrate in TCA cycle

Question 2

Regulation of PDHC Product Inhibition

Answer 2

inhibiting by NADH and Acetyl CoA (products_

• accumulate when not quickly oxidized by cycle or low O2.
• decrease PDHC pyruvate tehn shunted to lactate or oxaloacetate

Question 3

Regulation of PDHC covalent modification

Answer 3

PDH kinase

• NADH/AcCoA/ATP level increase all will activate PDH kinase
• PDH kinase Phosphorylates PDHC DEACTIVATING it
• high levels of pyruvate deactivate PDH Kinase by dephosphoryaltion

PDH Phosphatase:
increased Ca activates PDH phosphatase (from sarco reticulum)
-increases activity of PDHC by dephosphorylating it

Question 4

PDHC complex and dysfunction

Answer 4

5 coenzymes

• Thiamine B1 TPP
• Riboflavin B2 FAD
• Pantothenate B5 CoA
• Niacin B3 NAD+
• no precursor Lipoic acid

-vit B deficiency, extremely problematic especially with niacin

Question 5

PDHC deficiency

Answer 5

rare x linked or recessive reduction in PDHC levels

• all you need is 15% residual to function
• seen in infance, progressive neurological deterioration and eath

-acCoA cannot be made from Py, so you need to use other sources like FA, well brain cannot uptake FA and is always low on E

Question 6

TCA Cycle on and off times and definition

Answer 6

ALWAYS ON (rate changes)
-faster in fed

• mito matrix pathway
• ox of acCoA to CO2
• Energy via GTP NADH FADH2

Amphibolic: provides precursors to other anabolic and catabolic reactions

RegenerativeL product becomes substrate for next reaction and renewed each cycle

AcCoA + 3 NAD + FAD +GDP+ P + H2O ->
2Co2 + 3 NADH + FADH2 + GTP + #H + CoA
(EVERY TURN)

primary regulation of energy in cells.

Question 7

Regualtion of TCA rate

Answer 7

addition nof substrate only way to speed TCA
-adding AcCoA by itself does not lead to anything, those two carbos will lead to CO2

-also Acetly CoA will NEVER be substrate for glucose (can be ketone bodies)

Question 8

Pyruvate branch point

Answer 8

Pyruvate can either

Pyruvate dehydrogenase to ac Co A in Mito

pyruvate carboxylase, (OAA oxaloacetate in Mito)

lactate dehydrogenase (cytosol)

Question 9

TCA cycle Priming

Answer 9

2C from AcCoA and 4C from OAA needed to make citrate.

• E demand low, TCA slows, less OAA
• E demand high, TCA fast, more OAA
• routing py directly to OAA allows us to “prime” the cycle”

priming controlled by branch point, when acetyl coA is high, pyruvate dehydrogenase is inhibited, and pyruvate decarboxylase is activated

Question 10

Regulation of TCA by Citrate Synthase

Answer 10

Citrate synthase makes citrate from AcCoA and OAA,

• product inhibition of reaction
• citrate also allosterically inhibits PFK 1 and FA synthesis (both in cytosol)

Question 11

regulation of TCA by isocitrate dehyd

Answer 11

RATE LIMITING STEP

allowsteric inhibition by NADH ATP and activation by ADP and calcium

Question 12

regulation of TCA by alpha KGDHC

Answer 12

complex of three enzymes that require same 5 coenzymes as PDHC.

-prod inhibition by succinyl coA and NADH

Question 13

Thiamine Deficiency

Answer 13

necessary coenzyme for PDHC/aKGDH/branched chain Ketoacid dehydrogenase (breakdown of branched chains for energy-brain)

• impares glucose ox/accoA ox/cat of above
• highly aerobic like brain and muscle fail first
  arsenite: aso33- forms stable complex with thiol in lipoic acid, needed for above reaction.
• vascular degeneration, lesions,. gangrene, skin cancer

aso43- arsenate: subs Pi and allows glycolysis to skip phophoglycerate kinase- first atp generating step..

soooooooo