The TCA/Citric Acid/Krebs cycle Flashcards
glucose metabolism
The complete metabolism (i.e. to release all the energy) of glucose:
C6H12O6 + 6O2 -> 6CO2 + 6H2O
so far in glycolysis
glucose + 2NAD+ + 2ADP + 2Pi
2pyruvate + 2NADH + 2H+ + 2ATP + 2H2O
Note – no O2 in, and no CO2 out (yet).
What happens next to the pyruvate?
- it all depends on availability of oxygen
aerobic -> co2 +H2O ATP
Anaerobic-> lactic acid
anaerobic conditions
look at ppt for equation
- - Without this regeneration of NAD+ glycolysis stops and energy production comes to a full stop.
what happens to pyruvate in anaerobic conditions?
- Pyruvate is converted to lactate (lactic acid) by lactate dehydrogenase (LDH) – lactic acidosis is dangerous!
- This reaction is required in order to recycle NADH back to NAD+ to keep glycolysis going
- Net result = 2 ATPs per glucose
- Note: Anaerobic metabolism is inefficient ΔG for complete oxidation of glucose = -2886kJ per mole
- Energy in 2 ATPs ~= -114kJ per mole! (<5% of the total energy in glucose has been captured if just consider ATP).
in the presence of oxygen (aerobic)
- Pyruvate is transported into the mitochondria
- Pyruvate dehydrogenase (PDH) is in the mitochondria
- •PDH catalyses an irreversible reaction yielding CO2, NADH and acetyl CoA
look at ppt for diagrams
The citric acid cycle (or tricarboxylic acid cycle or the Krebs cycle)
- HUB” OF METABOLISM
- ITS AMPHIBOLIC(!) – CAN BE BOTH CATABOLIC AND ANABOLIC
- MAJOR SOURCE OF BIOSYNTHETIC PRECURSORS
- MAJOR SITE OF CARBOHYDRATE, AMINO ACID AND FATTY ACID OXIDATION
- 3NAD+ + FAD + GDP + ACTEYL-CoA + Pi -> 3NADH + FADH2 + GTP + CoA + 2CO2
arsenic poisoning
- arsenic (AsIII) compounds covalently bind sulphydryl compounds such as in lipoamide
- lipoamide containing enzymes such as pyruvate dehydrogenase (well it’s a complex of three enzymes really, see diagram) and -ketoglutarate dehydrogenase are thereby inactivated
- respiration ceases – this is, on the whole, not good
- organic arsenicals more toxic to microorganisms than humans. was used to treat syphilis and trypanosomiasis
- Fowler’s solution (a common tonic in the 1800s but used up to 1950s) was 1% arsenite. Interestingly arsenic-based drugs making a comeback in cancer therapy
- look at ppt
fluoracetate
Fluoroacetate is similar to acetate.
Fluoroacetate disrupts the Krebs cycle by combining with coenzyme A to form fluoroacetyl CoA, which reacts with citrate synthase to produce fluorocitrate
Fluorocitrate binds very tightly to aconitase, thereby halting the citric acid cycle.
This inhibition results in an accumulation of citrate in the blood.
lewisite (L)
-an organo-arsenic compound developed as a chemical weapon in WWI (but not used), acting as a vesicant (blister agent) and lung irritant.
- Lewis ite is a suicide inhibitor (an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms an irreversible complex with it through a covalent bond) of the E3 component of pyruvate dehydrogenase.
-
Peripheral nervous system pathology usually arises from
- Lewisite exposure as the nervous system essentially relies on glucose as its only catabolic fuel.
- ## As late as mid-2006, China and Japan were negotiating disposal of stocks of lewisite in north-eastern China, left by the Japanese military during World War II. Residents of China have died over the years from accidental exposure to stockpiles.
Krebs cycle only made how many more ATP
2
efficiency of only making 2 more ATP
- which hasn’t increased the efficiency much (although it is a 100% improvement) despite all that CO2 that suggests our glucose has been completely metabolised.
- we have generated a whole “load” (not an SI unit I admit) of NADH and FADH2 (reducing power)
- So Glycolysis and Krebs Cycle Combined leave us with
- Glucose consumed
- Six carbons converted to 6 CO2
- 4 ATPs produced
- 12 electron carriers produced
- 10 NADH
- 2 FADH2
