what can happen to pryuvate from glycolysis?
1) reduced to LACTATE via LDH in RBC, exercising muscle, embryonic tissue = ANAEROBIC GLYCOLYSIS
2) enter MITO for further metabolism by PDH to ACETYL CoA = AEROBIC GLYCOLYSIS
what does LDH reaction catalyze
reduces PYRUVATE to LACTATE
this is REVERSIBLE
why is LDH reaction important in RBC?
critical to RBC here b/c NADH reodixidzed back to NAD+, which is needed for glycolysis to continue at the G3PDH step
what do tissues w/ mito do with the LDH reaction?
oxidize the NAD+ from the LDH reaction to NADH after it is transported into the mito by the respiratory chain
how is LDH reaction improtant in muscle contraction?
reoxidizes NADH whenever glycolysis is very rapid - so when muscle contraction, high insulin levels, tumor cells
what is ANAEROBIC glucolysis?
glycolysis without oxygen
when lactate is the final product of glycolysis, and net of glycolysis is :
glucose + 2ADP + Pi -> 2 Lactic Acid + 2 ATP
what happens to lactate produced from LDH?
1) high levels of lactic acid leaves the RBC/muscle/tissue where it was produced, -> blood
high levels of lactate in blood alter blood pH, cause cramps, aggravate gout
2) other lactate enters tissues -> reoxidized back to pyruvate -> undergoes PDH reaction for energy production or can be converted to glucose in liver during gluconeogenesis
how does the RBC or brain or heart know which direction to go w/ the LDH reaction?
this question is b/c the LDH reaction is reversible
LDH is a tetramer made of 2H and 2M subunits;
therefore have 5 different isozymes/isoforms,
H4, H3M, H2M2, HM3, M4
where are the H vs. M isoforms of LDH found?
what are their properties?
H isoforms: brain, heart; have higher affinity for lactate and NAD; inhibited by high levels of pyruvate
M isoforms: RBC, skeletal muscle; have lower affinity for lactate and NAD; not inhibited by high levels of pyruvate
what happens to pyruvate in yeast cells?
it is converted to ethanol (alcohol) by pyrvuate decarboxylase
describe the pyruvate decarboxylase reaction
how pryvuate -> alcohol in yeast cells
pyruvate + TPP -> CO2 + acedylaldehyde, by pyruvate decarboxylase
acetylaldehyde + NADH -> ethanol + NAD, by alcohol DH
NET: glucose -> 2 ethanol + 2CO2 + 2ATP
what are mammals lacking re: alcohol fermentation rxn?
mammals do not have yeast pyruvate decarboxylase
thus mammals oxidize ethanol back to acetylaldehyde by alcohol DH, but that becomes acetyl CoA
otherwise, if we had pyruvate decarboxylase, glucose -> ethanol, as yeast do
what happens to pyruvate in most tissues?
undergoes the PDH reaction, converting it to acetyl COA
acetyl CoA can be further oxidized in the TCA cycle, generating NADH and FADH2 for energy production by the respiratory chain
what is the naure of the PDH rxn?
where does PDH reaction occur?
what is the net of the PDH reaction?
pryuvate + CoASH + NAD -> acetyl CoA + CO2 + NAHD + H
what does CoASH do?
carries acyl groups like acetyl and fatty acyl groups
contains B vitamin phosphopantethiene and an SH group at its terminus by which acyl groups attach
what are the enzymes of the PDH complex?
enzymes: E1, E2, E3, PDH kinase, phosphatase
vitamin cofactors: TPP for E1, lipoic acid for E2, riboflavin for E3, phosphopantetheine for CoASH, niacin for NAD+
describe the PDH mechanism
1) E1 decarboxylates pyruvate and replaces the CO2 w/ TPP
2) E2 replaces the TPP group w/ lipoamide. Then CoA is added to the reduced lipoamide
3) E3 reduces FAD, regenerating the lipoamide so that E2 is functional again - this matters so that acetyl CoA can keep being produced
what inhibits each step of the PDH mechanism? (metabolites)
ATP inhibits E1
Acetyl CoA inhibits E2
NADH inhibits E3
aka each of the reaction's products inhibits that reaction, and these are all signs of high energy
what hormonally controls the PDH reaction?
PDH Kinase: INHIBITS E1 by phosphorylating it; not effected by glucagon or epinephrine
INSULIN stimulates/increases PDH phosphatase: activates E1
what is unique about what happens in the E3 reaction of PDH?
reoxidation of FADH2 by NADH is the only case in metabolism in which FADH2 reduces HAD+ to NADH; usually, NADH reduces FAD to FADH2
what happens to C3, 4 of the original glucose?
comes off as CO2 in the PDH reaction
what happens to C1, 6 of the original glucose from glycolysis?
form the CH3 of acetyl CoA in PDH
what happens to carbons 2, 5 of the original glucose?
form the C=O of the acetyl group of PDH reaction
come off as CO2 in the TCA cycle
is PDH kinase sensitive to glucagon, epi?