krebs cycle Flashcards
glucose metabolism
C6H12O6 + 6O2 6CO2 + 6H2O
aerobic
co2+h20 ATP
anaerobic
lactic acid
see powerpoint for
anaerobic conditions diagram
without regeneration of NAD+…
glycolysis stops and energy production comes to a full stop.
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 presence of oxygen………………….. .Pyruvate is transported into the mitochondria
see powerpoint for
diagram of glycolysis in the cytoplasm
where is Pyruvate dehydrogenase
in the mitochondria
what does Pyruvate dehydrogenase do?
PDH catalyses an irreversible reaction yielding CO2, NADH and acetyl CoA
see powerpoint for
krebs cycle diagrams
what is 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
Thiamine is a component of TPP. Thiamine deficiency inactivates E1 and results in muscle weakness and loss of neural function)
Arsenic complexes with lipoamide and inactivates E3
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
an organo-arsenic compound developed as a chemical weapon in WWI (but not used), acting as a vesicant (blister agent) and lung irritant.
Lewisite 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.
end of krebs cycle
we have only made 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
