Glycolysis, Gluconeogenesis B&B Flashcards
what is dietary “fiber” made of?
cellulose - plant polysaccharide of glucose molecules that cannot be broken down by animals
adds bulk to improve bowel function
how do the following tissues differ in their use of glucose?
a. liver
b. brain
c. muscle/heart
d. RBC
e. adipose
a. liver - TCA for ATP, glycogen synthesis
b. brain - TCA for ATP, very little glycogen storage
c. muscle/heart - TCA for ATP, glucose uptake heavily influenced by insulin, stores glucose as glycogen but cannot release it into bloodstream (“selfish tissue”)
d. RBC - generates lactate (anaerobic metabolism for ATP, no mitochondria), HMP shunt for NADPH
e. adipose - converts glucose to fatty acids, uptake heavily influenced by insulin
where are GLUT-1 vs GLUT-2 vs GLUT-4 transporters found? how do they differ?
GLUT transporters: Na+ independent, following concentration gradient
GLUT1: brain, RBC - insulin independent (uptake when glucose is abundant)
GLUT2: liver, kidney, intestine, pancreas - insulin independent, bidirectional for gluconeogenesis
GLUT4: adipose, muscle - insulin dependent
Hexokinase vs glucokinase
hexokinase (most tissues): low Km + low Vm (hits max velocity quickly but max isn’t that fast); strongly inhibited by G6P but unaffected by insulin
glucokinase (liver, pancreas): high Km + high Vm + cooperativity (sigmoidal curve); induced by insulin, unaffected by G6P but inhibited by F6P (overcome by high [glucose])
under what 2 conditions is glucokinase inactive? explain why this makes sense
glucokinase (liver, pancreas): induced by insulin
inactive when there is 1. low glucose + 2. high F6P —> gluconeogenesis is favored
recall F6P (fructose-6-phosphate) is reversibly formed from glucose-6-phosphate
how do glucose and F6P both interact with glucokinase regulatory protein (GKRP)?
glucokinase regulatory protein (GKRP): translocates glucokinase into nucleus to inactive it
F6P (fructose-6-phosphate) - causes GKRP to bind glucokinase
glucose competes with GKRP for glucokinase binding —> keeps GK in cytosol (active)
how do the activity levels of hexokinase vs glucokinase differ in low and high blood sugar states?
what is the outcome of these differences?
low blood sugar: hexokinase is active, glucokinase inactive (low insulin) —> glucose enters tissues, not liver
high blood sugar: hexokinase inactive (inhibited by G6P), glucokinase active (high insulin) —> liver stores glucose as glycogen
what is the rate-limiting/committed step of glycolysis?
phosphofructokinase-1 converts fructose-6-phosphate to fructose-1,6-bisphosphate
requires ATP
(it’s a kinase - just adds another phosphate)
how does fructose-2,6-bisphosphate regulate glycolysis? where does it come from?
F-2,6-BP = on/off switch for glycolysis, high levels turn glycolysis ON / low levels promote gluconeogenesis
fructose-6-phosphate (substrate of PFK1, rate-limiting step) can be diverted to become fructose-2,6-bisphosphate by PFK2
F-2,6-BP can be converted back into F-6-P by F-1,6-BP2 … so when there is a lot of F-2,6-BP, it produces a substrate of glycolysis, thereby turning glycolysis ON
what effect does alanine have on glycolysis? explain why
alanine inhibits pyruvate kinase (3rd irreversible step)
skeletal muscle degrades protein, producing alanine, which travels to the liver… liver converts alanine to glucose via alanine transaminase (ALT), but in order to do so, must turn down glycolysis so that the newly produced glucose is not immediately broken down!
what is the function of ALT enzyme? what do high levels of this enzyme indicate?
ALT = alanine transaminase, converts alanine (amino acid) to glucose in the liver
high levels of ALT indicate liver damage
what effect do glucagon and epinephrine have on pyruvate kinase?
remember that
1. glucagon and epinephrine inhibit glycolysis and promote gluconeogenesis and
2. glucagon and epinephrine cause phosphorylation (via adenylyl cyclase —> cAMP —> PKA)
so (cheat code).. things that promote glycolysis will be inactivated by phosphorylation, and things that promote gluconeogenesis will be ACTIVATED by phosphorylation
so….. glucagon and epinephrine phosphorylate pyruvate kinase (irreversible enzyme of glycolysis), turning it OFF
how is pyruvate kinase deficiency inherited and how does it present?
autosomal recessive, presents as newborn —> extravascular hemolysis and splenomegaly
RBCs most effected because they do not have mitochondria - require pyruvate kinase for anaerobic metabolism… loss of ATP causes membrane failure —> phagocytosis in spleen
from what molecular pathway does 2,3 bisphosphoglycerate come from?
2,3 BPG diverted from 1,3 BPG in glycolysis
causes RBC to sacrifice ATP, but worth it because 2,3 BPG causes right shift to induce more O2 unloading in tissues
what enzymes catalyze the irreversible steps of glycolysis?
- hexokinase/glucokinase (glucose —> G6P) - ATP consumed
- PFK1 (F6P —> F1,6BP) - ATP consumed
- pyruvate kinase (PEP —> pyruvate) - ATP generated
