Intro to Metabolism, Regulation of Glucose Metabolism by insulin and glucose- Lecture 60 Flashcards
What is metabolism?
a sequence of enzyme-catalyzed reactions that brings about the transformation of substrate to products
What are the major functions of metabolism?
obtain and trap chemical energy from substrate, build precursors of macromolecules from the substrates, assemble the precursors into macromolecules, degrade macromolecules into simpler molecules
What is catabolism?
oxidative degradation of large nutrient macromolecules into smaller, simpler compounds
usually coupled with the release of energy
What is anabolism?
enzyme synthesis of larger molecular components of the cell from simpler precursors
usually requires input of energy
What are the means of regulation for metabolism?
Availability and concentration of substrates and cofactors
Availability/need for ATP
Enzyme characteristics
Regulatory enzymes-often allosteric
Genetic control of amount of enzyme in the cell
Hormone regulation (chemical messenger increase or decrease the rate of a metabolic rxn in another cell
What vitamins are fat soluble?
A (retinol), Provitamine A (beta-carotene), D, E, K
What vitamins are water soluble?
Thiamin, riboflavin, niacin, pantothenic acid, vitamin b, biotin, folate, vitamin b 12, vitamin c
Name the kinds of glucose transporters.
GLUT1 through GLUT5
Describe the high affinity glucose transporters.
GLUT 1 and 3 have a Km of 1 mM and are responsible for basal glucose uptake for almost all tissues (RBC, brain, heart, liver, etc.)
Describe the low affinity glucose transporter.
GLUT2 has a Km of 15-20 mM and senses high gluose levels; it is present only in the liver and the pancreas
Describe the intermediate affinity glucose transporter.
GLUT4 has a Km of 5 mM and is present in adipose and muscle, the amount of this is increased with insulin translocation from Golgi to plasma membrane
Describe the activity of GLUT5.
Mainly a fructose transporter; present primarily in GI tract and kidneys
What is passive carrier-medicated glucose transport?
ATP not required because glucose moves down its concentration gradient; blood glucose levels is maintained between 4-8 mM
What is active transport of glucose?
Moves molecules of glucose against their concentration gradient, so requires ATP or other energy source
What is insulin?
A peptide hormone released by the pancreatic beta cells in response to high glucose
What are the functions of insulin?
Increase glut4 in the membrane Increase glycolysis (decrease gluconeogenesis) Increase glycogen synthesis (decrease glycogen breakdown) Increase fatty acid synthesis and protein synthesis (decrease their breakdown)
How does insulin work?
Activates or inhibits rate-limiting enzymes in the pathways or increasing or decreasing synthesis of these enzymes at transcriptional or post-transcriptional levels
Glucagon is made by the _______ and works in the ______ by activating ______. Epinephrine is made by the _________ and works in ________ .
Alpha cells of the pancreas Liver and adipose g-protein coupled receptors Adrenals Most tissues (except RBCs)
Glucagon is released in response to _________ whereas epinephrine is released in response to _______.
Low blood glucose
Stress
What are the functions of glucagon and epinephrine?
Increase production of glucose, especially for use by brain, RBC, muscle/heart
How do glucagon and epinephrine function?
Increased gluconeogenesis and glycogen/fat/protein breakdown (opposite of insulin)
What is Type I DM?
Failure to produce insulin because of the destruction of pancreatic beta cells
What is Type II DM?
Failure to respond to the actions of insulin (insulin resistance)
What is the result of DM?
High blood glucose Impaired glucose utilization High glucose production Bioenergetic problems/failure to thrive Ketosis due to increased fatty acid metabolism Protein breakdown Increased glycosylation reactions (HbA1C) Osmotic pressure in eyes
______ pathways have both catabolic and anabolic components.
Amphibolic
Inhibitors of _______ will inhibit the enzyme but not likely the overall pathway.
non-rate-limiting enzymes
How much energy is release in the hydrolysis of one ATP?
7-8 Kcal/mol
As a general ‘rule’, glucagon and epi promote ________, whereas insulin promotes _______.
the phosphorylation of enzymes by activating cAMP-dependent PKA
the dephosphorylation of enzymes by activating certain phosphatases