lecture 25 - pentose phosphate pathway and specialisation of human metabolism Flashcards
What is the purpose of the pentose phosphate pathway?
uses glucose-6-phosphate
production of NADPH reducing power
synthesis of ribose-5-phosphate (for nucleotide biosynthesis)
The pentose ribulose-5-P generated during NADPH production is interconvertible with other pentoses.
The different pentoses are converted to intermediates of glycolysis to be metabolized further.
What is the oxidative stage?
Two step reaction, overall:
glucose-6-phosphate + 2NADP+ and H2O –> ribulose 5-phosphate + 2NADPH + CO2 + 2H+
first reaction is catalysed by glucose-6-phosphate dehydrogenase
second reaction involves ring opening (lactonase) followed by oxidative decarboyxylation by 6-phosphogluconate dehydrogenase
Generates 2 NADPHs and oxidizes one carbon to CO2
Both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase are highly specific for NADP+ over NAD+.
What is the non-oxidative stage?
Ribulose 5-phosphate usually converted back into glycolytic intermediates
products can enter gluconeogenesis or glycolysis
these are then converted to sugars with different numbers of carbon atoms using transaldoses which transfer 3 carbon units and transketolases which transfer 2 carbon units
The pentose phosphate pathway is reversible, and gluconeogenesis provides a way to reverse glycolysis. Therefore the intermediates can be shuttled between these pathways depending on the cell’s needs.
When both ATP and NADPH are needed G-6-P is used for NADPH generation in the pentose phosphate pathway.
To satisfy the ATP requirement, fructose-6-P and GAP are generated from ribose-5-P via the non-oxidative part of the pentose phosphate pathway. Glycolysis followed by the TCA cycle is then performed using fructose-6-P and GAP as starting points.
How can the pentose phosphate pathway function in reverse?
When a large amount of ribose-5-P is needed without the need for NADPH – for example during cell division when the DNA is replicated – the glycolytic intermediates fructose-6-P and GAP are used to produce ribose-5-P through the pentose phosphate pathway functioning in reverse.
Describe how the brain is specialised for metabolism
uses 20 % of our resting glucose consumption (120 g/day)– mainly for ion pumping
-has no energy stores (ie. no glycogen or TAG or fatty acids) as it lacks fuel stores it relies on liver to provide metabolisable fuels
glucose= main brain fuel in normal conditions- requires continuous glucose supply from liver via blood
glucose taken up from blood by GLUT1 transporter (largely insulin independent)
-cannot use fatty acids for fuel – if blood [glucose] decreases, the brain can use
ketone bodies for fuel
-is isolated from the body by the blood brain barrier (fatty acids cannot cross blood brain barrier, but water-soluble ketone bodies can cross)
on starvation, ketone bodies are used by the brain instead of glucose
Describe how muscle is specialised for metabolism
fuel store-has glycogen stores (¾ of the body’s glycogen)
can use glucose, fatty acids and ketone bodies as fuels
Glucose is taken up from the blood by GLUT4 transporter (insulin-dependent) in fed state
-lacks glucose-6-phosphatase (hangs on to its glucose)
Glucose released from endogenous glycogen stores (as G6P) stays in muscle cells, since no glucose-6-phosphatase is present (unlike liver)
In rapidly contracting (fast-twitch, white) muscle, glycolysis rates are far greater than oxygen supply, slo excess pyruvate is converted to lactate or alanine rather than entering TCA cycle
-releases nitrogen from amino acid catabolism in the form of alanine
-excess pyruvate is reduced to lactate (homolactic fermentation)
Lactate is transported to liver for conversion to glucose and trnasported back to muscle via the Cori cycle
skeletal muscle can operate anaerobically while heart muscle cannot – this is due to their differing isozymes of LDH. heart muscle is packed with mitochondria, but practically no glycogen – glycolysis is always aerobic – no lactate – fuels, uses glucose, fatty acids and ketone bodies.
In sprinting, muscle uses ATP, phosphocreatine and anaerobic glycolysis whereas in a marathon the fuel is roughly half glycogen (glucose) and half fatty acids (acetyl CoA)
Describe how adipose tissue is specialised for metabolism
Adipocytes:
-store triacyglycerol for energy (white fat)
TAG broken down into glycerol and fatty acids
glycerol converted to pyruvate by glycolysis or glucose by gluconeogenesis in liver cell
fatty acids oxidised in other tissues
Describe how the liver is specialised for metabolism
- is the metabolic control centre of the body
- all digested nutrients go to the liver (except FAs)
-controls the use of the three fuels
blood glucose ‘buffer’
