Chapter 16 Flashcards
What is the metabolite that links glycolysis and the citric acid cycle?
Pyruvate
Process in which cells consume O2 and produce CO2
cellular respiration
3 major stages of cellular respiration
- acetyl coA production
- acetyl coA oxidation
- electron transfer and oxidative phosphorylation
What molecule is required for the first step in the CAC?
acetyl coA
These types of molecules are not a permanent part of an enzyme’s structure, rather, they associate, fulfill a function and dissociate
Coenzymes aka cofactors
Advantages of multienzyme complexes
- the short distance between catalytic sites allows the channeling of substrates from one catalytic site to another
- this channeling minimizes side reactions
- the regulation of activity of one subunit effects the entire complex
What is substrate channeling?
The passage of intermediates from one enzyme directly to another enzyme without release (no exposure to solvent)
Where do oxidative reactions occur in the cell?
In the mitochondria which contains all the enzymes, coenzyme and proteins needed to carry out oxidation
Citrate formed from acetyl-coA and oxaloacetate is oxidized to yield …?
CO2
NADH
FADH2
GTP or ATP
What step is the rate-limiting step of the CAC
Step one - citrate synthesis- acetyl coA and oxaloacetate to citrate. It is highly thermodynamically favorable - irreversible
What is the end goal of citrate synthesis?
to fully oxidize both carbons in citrate that came from pyruvate to CO2 and generate ATP and electrons (NADH and FADH2) to be used in oxidative phosphorylation
What are the two regulatory proteins in the PDH complex?
protein kinase
phosphoprotein phosphate
Pyruvate is oxidized into what by the PDH?
pyruvate gets oxidized into acetyl coA and CO2
where does CAC occur
mitochondrial matrix
What step in the CAC is a substrate-level phosphorylation
step 5. the conversion of succinyl coA to succinate, produces GTP
What step does the first oxidative decarboxylation occur?
Step 3. The redox reaction of isocitrate to alpha-ketoglutarate
Which enzyme in the CAC is directly associated with the ETC?
succinate dehydrogenase
What products of the CAC are fed into the ETC for the generation of ATP?
FADH and NADH
What is the coenzyme of E1 in PDH complex?
TPP (thiamine pyrophosphate)
What is the coenzyme of E2 in the PDH complex?
lipollysine
What is the coenzyme of E3 in the PDH complex?
FAD
What two products are produced in the PDH complex?
acetyl coA and NADH
What steps are regulation points in the CAC?
PDH, citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase
- regulated at highly thermodynamically favorable and irreversible steps
What is the purpose of converting citrate to isocitrate?
citrate (tertiary alc) is a poor substrate for oxidation but isocitrate (secondary alc) is a good substrate for oxidation
What enzyme converts pyruvate to acetyl coA
Pyruvate dehydrogenase complex
what enzyme converts acetylcoA and oxaloacetate to citrate
citrate synthase
what enzyme converts citrate to isocitrate
aconitase
what enzyme converts isocitrate to alpha-ketoglutarate
isocitrate dehydrogenase
what enzyme converts alpha-ketoglutarate to succinyl coA?
alpha-ketoglutarate dehydrogenase
what enzyme converts succinyl coA to succinate
succinyl coA synthetase
what enzyme converts succinate to fumarate
succinate dehydrogenase
what enzyme converts fumarate to malate
fumarase
what enzyme converts malate to oxaloacetate?
malate dehydrogenase
what is the purpose of converting alpha-ketoglutarate into succinyl-coA?
alpha-ketoglutarate lacks an alcohol for oxidation so a thioester is formed on coA that can be oxidized
All CO2 generated during the CAC is produced before _______ is made
succinyl-coA
What does it mean that citrate is “pro-chiral”
it is not chiral but has the potential to react to generate a chiral species
can also react “stereospecifically” even though it is achiral
What is the purpose of converting succinyl coA to succinate?
This reaction produced GTP and creates succinate
What kinase converts GTP to ATP reversibly
Nucleoside Diphosphate kinase
What is the purpose of converting succinate to fumarate
succinate needs to be oxidized to an alkene (fumarate) since an alkene is needed to form malate in the correct stereochemistry in the next step
What molecule is a potent, competitive inhibitor of succinate dehydrogenase that blocks the CAC when added to mitochondria
Malonate, an analog of succinate
what is the purpose of converting fumarate to L-malate?
adding water across the pi bond of the alkene allows for oxidation to a ketone in the next step
**addition of water is always ANTI and forms L-malate
Fumarate must be (cis/trans)? in order to be recognized by fumarase
fumarate must be in the TRANS configuration
What is the purpose of converting malate to oxaloacetate?
the oxidation regenerates oxaloacetate for citrate synthase
What are anaplerotic reactions?
chemical reactions that replenish intermediates
What is the most important anaplerotic reaction in mammalian liver, kidney and brown adipose tissue?
pyruvate carboxylase catalyzes the carboxylation of pyruvate by HCO3
Explain the induced fit of citrate synthase
two conformations
conformational change occurs once oxaloacetate binds
open conformation: no binding site for acetyl-coA
closed conformation: binding of oxaloacetate creates a binding site for acetyl coA
What two molecules contain high-energy thioester bonds?
acetyl-coA and succinyl-coA
What coenzymes are used in all oxidative decarboxylation?
NAD+ and coA
What are the overall products of the CAC pathway?
NADH and ATP
How is the PDH complex regulated?
By phosphorylation of E1 and [ATP]
when E1 is phosphorylated it is INactive
when E1 is Dephosphorylated it is Active
High [ATP] –> PDH phosphorylated (inactive) –> less acetyl coA
Low [ATP] –> PDH DEphosphorylated (active) –> more acetyl-coA
