Chapter 9 - Carbohydrate Metabolism 1 Flashcards
What is normal blood glucose concentration?
around 100 mg/dL (5.6 mM), and the normal range is 4-6 mM
GLUT 2
low-affinity transporter in hepatocytes and pancreatic cells
GLUT 4
in adipose tissue and muscle, responds to the glucose concentration in peripheral blood; rate of glucose transport in these two tissues is increased by insulin
What happens to GLUT 4 transporters when insulin levels are decreased?
the number of GLUT 4 transporters on the plasma membranes decreases
What is the rate-limiting enzyme of glycolysis?
phosphofructokinase-1
What is the rate-limiting enzyme of fermentation?
lactate dehydrogenase
What is the rate-limiting enzyme of glycogenesis?
glycogen synthase
What is the rate-limiting enzyme of glycogenolysis?
glycogen phosphorylase
What is the rate-limiting enzyme of gluconeogenesis?
fructose-1,6-bisphosphatase
What is the rate-limiting enzyme of pentose phosphate pathway?
glucose-6-phosphate dehydrogenase
What is the importance of hexokinase?
in most tissues, inhibited by its product glucose-6-phosphate, low Km (reaches max velocity at low [glc]
What is the importance of glucokinase?
in hepatocytes and pancreatic beta-islet cells (along with GLUT 2), high Km, induced by insulin in hepatocytes
Phosphofructokinase-1 (PFK-1)
PFK-1 is rate-limiting enzyme and main control point in glycolysis, it’s inhibited by ATP and citrate, activated by AMP; insulin stimulates and glucagon inhibits PFK-1 in hepatocytes by an indirect mechanism involving PFK-2 and fructose 2,6-bisphosphate,
Phosphofructokinase-2 (PFK-2)
glucagon inhibits PFK-2, which lowers F2,6-BP and inhibits PFK-1, PFK-2 is mostly in the liver
Glyceraldehyde-3-Phosphate Dehydrogenase
catalyzes an oxidation and addition of inorganic phosphate (Pi) to its substrate; creates a high-energy intermediate 1,3-bisphosphoglycerate + reduction of NAD+ to NADH
3-PG Kinase
transfers high-energy phosphate from 1,3-BPG to ADP to form ATP and 3-PG
Substrate-Level Phosphorylation
ADP is directly phosphorylated to ATP using a high-energy intermediate
Pyruvate Kinase
catalyzes a substrate-level phosphorylation of ADP using the high-energy substrate PEP
Fermentation
key enzyme is lactate dehydrogenase which oxidizes NADH to NAD+, replenishes oxidized coenzyme for G3P; main objective is to replenish NAD+
Dihydroxyacetone phosphate (DHAP)
used in hepatic and adipose tissue for triacylglycerol synthesis; DHAP is formed from F1,6-BP, can be isomerized to G3P which can convert to glycerol
How is ATP gained during anaerobic respiration?
1,3-BPG and PEP are high-energy intermediates used to generate ATP by substrate-level phosphorylation
How Glycolysis Pushes Forward the Process: Kinases
Hexokinase, Glucokinase, PFK-1, Pyruvate Kinase
How does adaptation to high altitudes (low pO2) work?
Increased respiration, increased O2 affinity for Hb (initial), increased rate of glycolysis, increased [2,3-BPG] in RBCs (12-24 hr period), normalized O2 affinity for Hb restored by the increased level of 2,3-BPG, increased Hb (over days to weeks)
Glycolysis in Erythrocytes
anaerobic glycolysis represents the only pathway for ATP production, yielding a net 2 ATP per glucose
Why do red blood cells have bisphophoglycerate mutase?
to produce 2,3-BPG from 1,3-BPG in glycolysis
2,3-BPG
binds allosterically to the beta-chains of hemoglobin A (HbA), decreases affinity for O2, goal is to unload O2 in tissues
What physiological changes promote a rightward shift of the oxygen dissociation curve (the Bohr effect)?
High 2,3-BPG, low pH, high [H+], high pCO2
The Bohr Effect
increases in CO2 partial pressure of blood or decreases in blood pH result in a lower affinity of Hb for O2
Galactose Metabolism
lactose is a disaccharide that is hydrolyzed to galactose and glucose by lactase
Pyruvate Dehydrogenase Complex (PDH)
irreversible, cannot be used to convert acetyl-CoA to pyruvate or glucose, activated by insulin in the liver, in the nervous system it is not responsive to hormones
Glycogenesis
synthesis of glycogen granules, begins with a core protein called glycogenin
Glycogen Synthase
rate-limiting enzyme of glycogen synthesis, and forms the alpha-1,4 glycosidic bond found in the linear glucose chains of the granule, stimulated by G6P and insulin, it is inhibited by epinephrine and glucagon through a protein kinase cascade that phosphorylates and inactivates the enzyme
Branching Enzyme (Glycosyl alpha-1,4:alpha-1,6 Transferase)
introduces alpha-1,6-linked branches into the granule; hydrolyze one of the alpha-1,4 bonds to release a block of oligoglucose, which is moved and added to a slightly different spot via an alpha-1,6 bond to make a branch
Glycogen Phosphorylase
breaks alpha-1,4 glycosidic bonds, releasing G1P from periphery of granule
Debranching Enzyme (Glucosyl alpha-1,4:alpha-1,4 Transferase and alpha-1,6 Glucosidase)
two-enzyme complex: one moves the terminal end of a glycogen chain to the branch point (alpha-1,4:alpha-1,4 transferase), and one removes glucose monomer at branch point (alpha-1,6)
What are important substrates of gluconeogenesis?
Glycerol-3-phosphate
Lactate (from anaerobic glycolysis)
Glucogenic amino acids (from muscle proteins)
What are glucogenic amino acids?
All AAs except leucine and lysine, can be converted to intermediates that feed into gluconeogenesis
What are ketogenic amino acids?
can be converted into ketone bodies, can be used as an alternative fuel mainly during prolonged starvation
Pentose Phosphate Pathway (PPP) or Hexose Monophosphate (HMP) Shunt
two major functions: production of NADPH and serve as a source of ribose 5-phosphate for nucleotide synthesis
Glucose-6-phosphate Dehydrogenase
rate-limiting enzyme of the PPP which is activated by NADP+ and insulin; inhibited by NADPH
