L9 - Controlling the fate of pyruvate Flashcards
Pyruvate: its possible pathways
PEP -> pyruvate (PK)
Pyruvate -> Oxaloacetate (PC)
Pyruvate -> Acetyl CoA (PD)
PEP -> pyruvate: what is the enzyme that catalyses this reaction, and where does it occur?
Pyruvate kinase
Cytosol
(PEP = Phosphoenolpyruvate)
Pyruvate -> Oxaloacetate: what is the enzyme that catalyses this reaction, and where does it occur?
Pyruvate carboxylase
Mitochondria
Pyruvate -> Acetyl CoA: what is the enzyme that catalyses this reaction, where does it occur, and what uses does Acetyl CoA do?
Pyruvate dehydrogenase
Mitochondria
- oxidation directly into the citric acid cycle or indirectly after converting into fatty acids
- Retention of pyruvate via gluconeogenesis, to glucose or glycogen
- Isoenzymes and tissue-specific expression
Oxaloacetate -> PEP: what is the enzyme that catalyses this reaction, and where does it occur?
PEPCK - PEP carboxylase kinase
Mitochondria -> cytosol
The mitochondrial fate of pyruvate: what is pyruvate transformed into, what enzymes catalyse this reaction, what bi-reactions occur, and what tissues do they mainly occur in?
Pyruvate -+ CoA + NAD -(PD)> Acetyl CoA + CO2 + NADH
* All cells with mitochondria
Pyruvate -(PC)> Oxaloacetate + CO2
* Liver, kidney, muscle, adipose
Acetyl CoA: what uses does it have in the body?
Production of:
* Sterols
* Ketones
* Oxidation
* Fatty acids, triglycerides, and/or phospholipids for oxidation in TCA
Oxaloacetate: what uses does it have in the body?
- Transamination
- Replenish citric acid cycle intermediates
- Glucose
PDH: what is it, what does it do, and how is it regulated?
Pyruvate dehydrogenase
Major control of activity by phosphorylation
Allosterically regulated - activated by PDH phosphorylase and deactivated by PDH kinase
PDH kinase regulation
PDH kinase is regulated allosterically by metabolites, displaying feedback inhibition:
* Activated by acetyl CoA and NADH (PDH products)
* Inhibited by Pyr, CoA, NAD (PDH substrates)
* Inhibited by ADP (an indicator of cellular energy status)
- PDH “products” (eg acetyl CoA) are also produced from fatty acid oxidation – allows co-ordination of glucose and fat oxidation
PDH phosphatase regulation: what is it regulated by and what does it work with in starvation?
PDH phosphatase activated by insulin signalling (an indicator of “incoming” glucose-derived pyruvate)
Co-ordinates with fatty acid utilisation in starvation
Glucose use in Acetyl CoA production: when does it occur and why is it not always needed?
Only really happens when glucose is in abundance, allosteric inhibitors of PDH and PFK (phosphofructokinase) are produced in the glucose->citric acid cycle
Acetyl CoA may be generated by glucose, fatty acid, ketones, and amino acids - glucose doesn’t need to always be used
Citric acid cycle and regulation
ATP allosterically inhibits enzymes for the cycle, meaning regulation occurs
PC: what is it, how is it regulated, and when is it (not) synthesised?
Pyruvate carboxylase
- Allosteric activation by acetyl CoA (starvation causes increased production from fatty acid)
The generation of proximal promoter transcripts are:
* Increased in response to glucagon (PKA) and glucocorticoids (nuclear receptors)
* Decreased in response to insulin (signalling)
Relevance to hormone changes in starvation and need to enhance liver capacity for gluconeogenesis
PEP/Pyr cycles: what forms are there, what are they encoded by, how are they regulated, and where do they occur?
Two isoforms encoded by separate genes:
* One localised to cytosol - AA (alanine) to glucose conversion
* One localised to mitochondria - Cori cycle, lactate-glucose conversion
Differential roles and regulation (cytosolic form inducible)
Liver, kidney, skeletal muscle, intestinal mucosa, and adipose
