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Gluconeogenesis Quantitative importance: Daily glucose requirements Brain 110 Muscle Renal Medulla Red Blood Cells Intake
~ 100 g Stores Liver Glycogen Blood Glucose
(g) 30 30 25
70 g 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:
1. In liver
2. (to lesser extent) in kidney These tissues are important as they contain a specific enzyme, glucose-6phosphatase, which allows release of free glucose from the cell glucose-6-phosphate?glucose + 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
mitochondrion glucose oxaloacetate oxaloacetate 2 ATP2 NADH 2 NAD
malate malate 'NH 3' pyruvate alanine respiratory chain 5 ATP Glutamine: produced primarily from muscle and is derived from catabolism of branched chain amino acids. The glutamine is then transported into the liver.
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