carbohydrate metabolism 2 Flashcards
Pentose Phosphate Pathway
Thepentose phosphate pathwayis a metabolicpathwayparallel to glycolysis.
It generates NADPH andpentoses(5-carbon sugars) as well asribose 5-phosphate, a precursor for the synthesis of Nucleotides.
There are two distinct phases in the pathway. The first is theoxidativephase, in which NADPH is generated, and the second is the non-oxidativesynthesisof 5-carbon sugars.
For most organisms, the pentose phosphate pathway takes place in thecytosol.
The primary results of the pathway are:
The generation of reducing equivalents, in the form of NADPH, used in reductive biosynthesis reactions within cells (e.g.fatty acid synthesis).
Production ofribose 5-phosphate(R5P), used in the synthesis ofnucleotidesand nucleic acids.
Production oferythrose 4-phosphate(E4P) used in the synthesis ofaromatic amino acids.
Gluconeogenesis
Conversion of pyruvate to glucose from non-carbohydrate precursors
Important for the maintenance of blood glucose levels during starvation or vigorous exercise
Occurs mainly in the liver and to a lesser extent in the kidney
Some enzymes of this pathway are present in mitochondria, most are found in the cytosol
Precursors for Gluconeogenesis
Lactate
Glycolysis generates lactate in active muscle; RBCs steadily produce lactate
In liver, converted to pyruvate (substrate for gluconeogenesis) by the action of lactate dehydrogenase.
Glucose produced by liver enters the bloodstream for delivery to peripheral tissues
-> Cori Cycle
Conversion of lactate to glucose requires energy which is derived from the oxidation of fatty acids in the liver.
Cori Cycle
Metabolism under conditions of vigorous exercise (limited oxygen)
Represents the transfer of chemical potential energy in the form of glucose from the liver to peripheral tissues
Maintaining blood glucose within strict limits
Glucose is the major metabolic fuel
Brain almost entirely relies on glucose for energy and if blood glucose falls, glucose uptake into the brain is compromised.
Liver is involved in the inter-conversions of metabolic fuels – CHO, AAs and FAs.
When dietary glucose is consumed by tissues, liver glycogen and gluconeogenesis (from lactate, glycerol and alanine) become the sources of glucose.
Other tissues generate ATP by oxidising FAs mobilised from adipose tissue.
Glycogenolysis: Glycogen Degradation
Glycogenolysisis the breakdown ofglycogen toglucose-6-phosphateandglycogen. Glycogen branches are catabolizedby the sequential removal of glucose monomers viaphosphorolysis, by the enzymeglycogen phosphorylase.
Function of Glycogenolysis
Glycogenolysis takes place in the cells of themuscleandlivertissues in response to hormonal and neural signals.
In particular, glycogenolysis plays an important role in thefight-or-flight responseand the regulation of glucose levels in the blood.
Inmyocytes(muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for glycolysis, to provide energy for muscle contraction.
Inhepatocytes(liver cells), the main purpose of the breakdown of glycogen is for the release of glucose into the bloodstream for uptake by other cells.
Regulation and Clinical Significance: of glycogenolysis
Glycogenolysis is regulated hormonally in response to blood sugar levels byglucagonandinsulin, and stimulated byepinephrineduring thefight-or-flight response.
In myocytes (muscle cells), glycogen degradation may also be stimulated by neural signals.
Parenteral (intravenous) administration ofglucagonis a common human medical intervention indiabeticemergencies when sugar cannot be given orally.
It can also be administeredintramuscularly.
Glycogenesis: Glycogen Synthesis
Glycogenesisis the process ofglycogensynthesis, in whichglucosemolecules are added to chains of glycogen for storage.
This process is activated during rest periods following theCori Cycle, in theliver, and also activated byinsulinin response to high glucose levels, for example after acarbohydrate-containing meal.
Glycogenesis,the formation ofglycogen, the primarycarbohydratestored in theliverandmuscle cells of animals, fromglucose.
Glycogenesis takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells.
Glycogenesis is stimulated by thehormoneinsulin.
Insulinfacilitates the uptake of glucose into muscle cells, though it is not required for the transport of glucose into liver cells.
However, insulin has profound effects on glucosemetabolismin liver cells, stimulating glycogenesis andinhibiting glycogenolysis, the breakdown of glycogen into glucose.
Compatibility of Glycogenesis and Glycogenolysis
As is the case with glycolysis and gluconeogenesis, it would be futile for the cell to carry out glycogen synthesis and degradation simultaneously.
The results achieved by the action of one pathway would be undone by the other.
This problem is avoided by a series of hormonal controls that activate the enzymes of one pathway while inactivating the enzymes of the other pathway.
Hyperglycemia
While the blood glucose level is too high, a condition known as hyperglycemia, insulin stimulates the uptake of glucose via a transport mechanism.
It further stimulates the trapping of the glucose by the elevated activity of glucokinase.
Hypoglycemia
While the blood glucose level is too low, a condition known as hypoglycemia, and has an effect opposite to that of insulin.
It stimulates glycogen phosphorylase, which catalyses the first stage of glycogen degradation.
This accelerates glycogenolysis and release of glucose into the bloodstream.
The effect is further enhanced because glucagon inhibits glycogen synthase.
Causes of Hyperglycemia
Diabetes mellitus
Chronic hyperglycemia that persists even in fasting states is most commonly caused bydiabetes mellitus.
Drugs
Certain medications increase the risk of hyperglycemia includingcorticosteroids,betablockers,epinephrine,thiazidediuretics,niacin, pentamidine,protease inhibitorsand someantipsychoticagents.
Critical illness
A high proportion of patients suffering an acute stress such asstrokeormyocardial infarctionmay develop hyperglycemia, even in the absence of a diagnosis of diabetes. Stress-induced hyperglycemia is associated with a high risk of mortality after both stroke and myocardial infarction.
Stress
Treatment of Hyperglycemia
Treatment of hyperglycemia requires elimination of the underlying cause, such as diabetes.
Acute hyperglycemia can be treated by direct administration of insulin in most cases.
Severe hyperglycemia can be treated withoral hypoglycemic therapyand lifestyle modification.
Causes of Hypoglycemia
Medications used to treatdiabetes mellitussuch asinsulin,sulfonylureas, andbiguanides. Risk is greater in diabetics who have eaten less than usual, exercised more than usual, or drunkalcohol.
Other causes of hypoglycemia includekidney failure, certaintumors,liver disease,hypothyroidism,starvation,inborn errors of metabolism,severe infections,reactive hypoglycemia, and a number of drugs including alcohol.
Inborn errors of metabolism may include the lack of an enzyme to make glycogen (glycogen storage type 0).
Serious illness Serious illness may result in low blood sugar. Severe disease of nearly all major organ systems can cause hypoglycemia as a secondary problem.Hospitalizedpersons, especially inintensive care unitsor those prevented from eating.
Hormone deficiency Not enough cortisol, such as inAddison’s disease, not enough glucagon, or not enough epinephrine can result in low blood sugar.This is a more common cause in children.
