1. Metabolism Of Glucose Flashcards
Metabolic adaptations during starvation?
First Stage: Glycogenolysis
During fasting, at first, blood glucose level is maintained by hepatic glycogenolysis. The glycogen stores are sufficient for about 18 hours. The primary requirement for glucose is to meet the demands of the brain.
Second Stage: Gluconeogenesis
Even before the glycogen stores are depleted, gluconeogenesis is accelerated (Fig.8.3). The amino acids released from muscle form the major substrate for gluconeogenesis. The amino nitrogen is transferred from other amino acids to pyruvate to form alanine. Thus the amino group reaches the liver as alanine where it is transaminated to give pyruvate for gluconeogenesis. This glucose alanine cycle (Fig. 9.30) serves to transport the amino nitrogen of other amino acids to liver in a harmless form. Glutamic acid also serves as an important mode of transport of amino acids to liver.
The branched chain amino acids liberated by muscle protein catabolism especially leucine and isoleucine are utilized by the muscle to give energy. Brain can preferentially take up the glucogenic valine from the blood stream. The plasma level of branched
Chapter 8; Overview of Metabolism 89 chain amino acids reaches a peak by 5th day of
starvation.
Third Stage: Lipolysis
The prevailing state of high glucagon-insulin ratio stimulates cAMP mediated lipolysis by increasing the activity of hormone sensitive lipase. Then skeletal muscle, heart and kidney will shut down their glucose utilization; and will depend mainly on fatty acids for energy needs (glucose-fatty acid- cycle). Inactivation of pyruvate dehydrogenase by phosphorylation is the basis of this change. The stimulation of the activity of CAT by glucagon favors increased rate of beta oxidation. The increased rate of lipolysis and beta oxidation provides an alternate source of fuel as acetyl CoA and subsequently ketone bodies. Ketone bodies provide fuel for tissues like heart muscle, skeletal muscle and to some extent the brain. It is seen that brain starts utilizing ketone bodies from 3rd day of starvation. By 10th day of starvation about 60% of energy for brain is derived from ketone bodies.
Fourth Stage: Acidosis
However, this state cannot continue indefinitely since excessive production of ketone bodies leads to metabolic acidosis. When the bicarbonate buffering capacity is exceeded, the pH falls and hyperventilation occurs as a compensatory mechanism.
Fifth Stage: Death from Starvation
Metabolic acidosis and dehydration, unless corrected efficiently, will lead to death. A normal person has fuel reserves to live up to 45–60 days
Fifth Stage: Death from Starvation
Metabolic acidosis and dehydration, unless corrected efficiently, will lead to death. A normal person has fuel reserves to live up to 45–60 days.
Explain lactose intolerance?
Lactase hydrolyses lactose to glucose and galactose.
Lactase is present in the brush border of enterocytes.
Def. of lactase leads to lactose intolerance which causes irritant diarrhoea flatulence vomiting etc. on ingesting lactose.
Lactase is naturally produced in infants to digest milk. However as one gets older this production may be stopped.
It may also be stopped due to some disease or abnormality.
It can be congenital aka primary (rare and recessive gene), or acquired aka secondary.
If milk is withdrawn temporarily, the diarrhoea will be limited. Curd is also an effective treatment, because the lactobacilli present in curd contains the enzyme lactase. Lactase is abundantly seen in yeast, which could also be used in treatment.
Digestion of Carbohydrates
i. Inthedietcarbohydratesarepresentascomplex polysaccharides (starch, glycogen), and to a minor extent, as disaccharides (sucrose and lactose). They are hydrolysed to mono- saccharide units in the gastrointestinal tract. Cooking makes the digestion process easier.
ii. This process of digestion starts in mouth by the salivary alpha-amylase. However, the time available for digestion in the mouth is limited, because the gastric hydrochloric acid will inhibit the action of salivary amylase.
iii. Inthepancreaticjuiceanotheralpha-amylase is available which will hydrolyse the alpha-1,4 glycosidic linkages randomly, so as to produce smaller subunits like maltose, isomaltose, dextrins and branched or unbranched oligo- saccharides.
iv. The cells of brush border of intestine contain the enzymes, sucrase, maltase, isomaltase and lactase. They hydrolyse the corresponding disaccharides into component monosaccha- rides which are then absorbed.
HK vs GK
Glucokinase that is active mainly in liver has a high Km for glucose and low affinity. Hence, glucokinase can act only when there is adequate glucose supply so that excess can be stored. Hexokinase with low km and high affinity can phosphorylate glucose even at lower concentrations so that glucose is made available to brain, cardiac and skeletal muscle. Glucokinase can act only when there is plenty of glucose. Thus, when the supply of glucose is limited, glucose is made available to brain and muscles.
Occurrence Km value Specificity Function Hexokinase In all tissues 10-2 mmol/L Acts on glucose, fructose and mannose Even when blood sugar level is low, glucose is utilized by body cells Glucokinase Only in liver 20 mmol/L Acts only on glucose Acts only when blood glucose level is more than 100 mg/dl; then Glucose is taken up by liver cells for glycogen synthesis
Malate Aspartate Shuttle?
The carboxylation of pyruvate(first step in gluconeogenesis) to form oxaloacetate takes place in mitochondrion. The rest of the reaction takes place in cytosol hence oxaloacetate has to be transported from mitochondria to cytosol. Oxaloacetate is first converted to malate, which traverses the membrane and reaches cytoplasm. Malate is then re-converted to oxaloacetate. Malate dehydrogenase is present in both mitochondria and cytoplasm. Oxaloacetate may also be transported as aspartate formed by transamination of oxaloacetate.
