0218 - Carbohydrate Metabolism - RM Flashcards
What is a Carbohydrate
A macromolecule consisting of Carbon, Hydrogen, and Oxygen atoms. The ‘base’ carbohydrate in the body is the monosaccharide Glucose.
List 5 roles that Carbohydrates have in the cell
Many roles - Energy Storage (glycogen) Provision of energy (glycolysis->pyruvate->TCA cycle)Assist in regulating processes (glycoproteins and glycolipids)Provide body’s structure through the amino sugar glycosaminoglycan (GAG).Provide ribose for DNA and RNA.
Describe two ways in which carbohydrates can form structural molecules
Glycosylation - the attachment of carbohydrates to pre-existing proteins to form glycoproteins. This occurs in the Golgi Apparatus (‘putting on the jewellery’, and gives the protein structure and function that it did not previously have.Glycoseaminoglycans (GAGs) are the main form of structural carbohydrates and are linear, unbranched polymers of repeating disaccharide units with an amino sugar attached. They have a large negative charge (attract water). This gives them valuable qualities that makes them used throughout the body. When they are bonded to proteins as proteo-glycans, they form a mesh-like network providing strength, support and protection through the body.
What are the three functions that involve the storage/mobilisation of carbohydrates?
Glycogenolysis - The mobilisation of glucose from glycogen under conditions of low blood sugar (7mM). Accompanied by increased hepatic glucose uptake.Gluconeogenesis - Hepatic scavenging of precursors (incl lactate) to synthesise glucose to ensure sufficient supply to the brain.
Describe the process of glycogenesis
Glycogenesis is the storage of glucose as glycogen (anabolic process).GLUT-2 passively transports glucose across the cell wall (thus a key regulation), where it is quickly phosphorylated into Glucose-6-Pi by Glucokinase and ATP (hexokinase outside the liver in high blood sugar conditions). Glucose-6-Pi cannot be transported out of the liver and doesn’t affect glucose concentration gradient, allowing GLUT-2 to continue passive transport.From here, it is converted into glucose-1-Pi and glucose residue (UDP glucose).The glucose residues join glycogenin, and are formed into the glycogen polymer by GLYCOGEN SYNTHASE - a single, monosaccharide polymer with branch points every 8-10 residues. Glycogen synthase is stimulated by insulin.
Describe the catabolism of carbohydrates
The presence of adrenaline (in muscle) and glucagon (in liver) increases the amount of cyclic AMP. This activates protein kinase A, which indirectly activates GLYCOGEN PHOSPHORYLASE, and inhibits GLYCOGEN SYNTHASE. This starts the GLYCOLYTIC PATHWAY which takes place in the cytosol.Glycogen phosphorylase removes glucose molecules from glycogen. The glucose is catabolysed into 2 pyruvate, and providing 2 reduced cofactors NADH (link to TCA cycle) and 2 ATP. The committed step for this reaction is the conversion of fructose-6-Pi by PFK.Regulation takes place in a number of ways, with regulated steps between ‘pools’ of interconvertible intermediates. The activity of Pyruvate Kinase (PK) is highly regulated. The overall pathway is also regulated by the cell’s redox state (ATP/ADP and NADH/NAD levels).
How is carbohydrate metabolism maintained in cells?
Under aerobic conditions, carbohydrate metabolism in cells is maintained through the TCA cycle in the mitochondria. Oxygen is vital to continuing the electron transport chain, generating maximum energy and allowing NAD to be recycled.Under anaerobic conditions, carbohydrate metabolism proceeds to pyruvate, at which point it is shunted to lactate (to be recycled in the liver). However, this is not sustainable (does not provide sufficient energy) and the cell will ultimately shut down and die.
Catabolic Process as metabolic provider
Glycolysis is about more than providing energy. It also provides bases for nucleotides (ribose), higher order lipids, and substrate for the pentose-phosphate pathway. In addition to these key intermediates, pyruvate can be converted to acetyl-CoA, which is inter-convertible with effectively every metabolic pathway.Ultimately, glycolysis provides the building blocks for proteins, lipids, and nucleotides.
Where does Glycolysis take place?
In the cytosol. Once pyruvate has been formed it can move into the mitochondrial matrix for acetyl-CoA synthesis (very regulated step).
Briefly describe the regulation of glycolysis
Glycolysis is activated by the presence of adrenaline and glucagon (hormones), as well as by the redox state in the cell (relative [ATP]/[ADP], [NADH]/[NAD]).Glycolysis involves a committed step in the phosphorylation of Fructose-6-P by PFK.It also has branch points (glucose-6-P), a link to the TCA cycle (GA3PDH), co-regulation between glycogen phosphorylase and glycogen synthase, and compartmentalisation (between Pyruvate and Acetyl-CoA).