Medicine Notes Biochemistry Notes
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Gluconeogenesis
Quantitative importance:
Daily glucose requirements (g)
Brain 110
Muscle 30
Renal Medulla 30
Red Blood Cells 25
Intake ~ 100 g
Stores
Liver Glycogen 70 g
Blood Glucose 15 g
On fasting, stores only sufficient for ~12 hours
Glucose from diet is too valuable a resource to be used unless necessary
To reduce dietary glucose utilisation and provide glucose during fasting, a wide range of compounds can be used to synthesise glucose and maintain glycogen stores
GLUCONEOGENESIS TAKES PLACE:
In liver
(to lesser extent) in kidney
These tissues are important as they contain a specific enzyme, glucose-6-phosphatase, which allows release of free glucose from the cell
glucose-6-phosphateglucose + Pi
-Under normal circumstances, liver is almost always a net exporter of glucose
-Other tissues are net users of glucose – do not have glucose-6-Pase
synthesis of glucose from non-carbohydrate sources
-occurs during longer period of fasting/ starvation- it maintains levels of glucose which is important for the brain as it depends on glucose as its primary fuel and RBC as they use glucose as their only fuel
-gluconeogenic pathway converts pyruvate into glucose
-main site for gluconeogenesis is the liver, with a small amount taking place in the kidney
Glucogenic precursors
-other sugars: Fructose, galactose- period after meal, these sugars are used to replenish glycogen stores
Lactate-formed by anaerobic glycolsysi by muscle/ renal medulla/ RBC when rate of glycolysis > rate of oxidative metabolism
-Cori cycle: The lactate formed enters the circulation where it enters the liver. Lactate dehydrogenase converts lactate into pyruvate which is then converted into glucose. The glucose is then transported to the skeletal muscle for further oxidation, allows generation of ATP in the abscence of glucose
Amino acids: alanine, glutamine- derived from proteins in the diet/ breakdown of protein from skeletal muscle
Alanine: generated in muscle when carbon skeletons of some amino acid are used as fuels. Nitrogens from these amino acids are transferred to pyruvate to form alanine. This reaction occurs under less extreme conditions, when cytoplasmic NADH can be reoxidised using mitochondrial shuttles
-alanine produced in large amounts in muscles on fasting and is sent to the liver for gluconeogenesis- four times as much ATP and removes NH3
Glutamine: produced primarily from muscle and is derived from catabolism of branched chain amino acids. The glutamine is then transported into the liver.
Glycerol: hydrolysis of triglycerides releases fatty acids and glycerol in adipose cells. Glycerol can’t be reused by adipose cells. So glycerol is transported into the liver where glycerol kinase converts glycerol into glycerol-3-P. The glycerol-3-P is then oxidised into glyceraldehydes-3-P which is converted into glucose.
-Even chained fatty acids can’t be used to synthesise glucose. Beta oxidation produces acetyl coA but this can’t be converted back into pyruvate as pyruvate into acetyl CoA is an irreversible reaction. Even if acetyl coA enters the TCA cycle it will be completely oxidised and the 2 carbons of the acetyl coA is given off as 2 CO2 molecules.
Reactions of gluconeogenesis
-in glycolysis glucose is converted into pyruvate, in gluconeogenesis pyruvate is converted into glucose
-gluconeogenesis is not a reversal of glycolysis- several reactions must differ as the equilibrium of glycolysis lies far on the side of pyruvate formation
-there are three irreversible steps in glycolysis
-Glucose glucose-6-P (catalysed by...
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