Flashcards in Carbohydrate Metabolism Deck (74):
Ubiquitous, but high in RBCs and brain.
High affinity for Glc. (Unreg.)
Main transporter in liver.
Low affinity for Glc. (Unreg.)
Main transporter in neurons.
High affinity for Glc. (Unreg.)
Present in skeletal muscle, heart and adipose tissue.
More on GLUT 4:
Sequestered in vesicles.
Insulin signaling causes fusion of vesicle w/ PM.
Enables uptake of Glc.
3 Phases of Glycolysis
Net Yield of Glycolysis
2 ATP, 2 NADH, 2 pyruvate
Investment Phase (3)
1. Phosphorylation of Glc to G6P (use ATP)
2. Isomerization of G6P to F6P
3. Phosphorylation of F6P to F 1,6-BP (RLS and uses ATP)
Splitting Phase (2)
4. Cleavage of F 1,6-BP (now two 3C molecules)
Payoff Phase (3)
6. Phosphorylation of G3P (Reduces NAD+ to NADH x 2)
7. Conversion of 1,3-BPG to 3-PG (1 ATP)
8. Formation of pyruvate (1 ATP)
Enzymes Catalyzing ATP using/producing Reactions and Produce NADH
1. Hexokinase/glucokinase - Glc to G6P (1 ATP)
3. PFK-1 - F6P to F 1,6-BP (1 ATP)
6. Glyceraldehyde 3-P DH - G 3-P to 1,3-BPG (2 NADH)
7. Phosphoglycerate kinase - 1,3-BPG to 3-PG (1 ATP)
10. Pyruvate kinase - PEP to pyruvate (1 ATP)
Checkpoints of Glycolysis (3)
10. Pyruvate kinase
3 Checkpoint Enzymes Influenced by (4):
ATP, AMP, insulin, glucagon
Present in all cells.
High affinity (even when Glc is low).
Inhibited by G6P.
Present in liver and pancreatic beta cells.
Low affinity for Glc.
Not inhibited by G6P.
At low [Glc], translocates to nucleus.
+ AMP, F 2,6-BP
- ATP, citrate
Hormonal Regulation of PFK-1 (2)
+ Insulin, - Glucagon
1. When insulin is high: dephosphorylates FBPase-2 produces F 2,6-BP, which activated PFK-1.
2. When insulin is low (glucagon is high): Induces cAMP, phosphorylates PFK-2, reduces PFK-1 activity.
Catalyzes conversion of PEP to pyruvate and ATP.
Regulation of PK
+ by F 1,6-BP and insulin
- by ATP, Alanine, and Glucagon
High insulin: activates PK
Low insulin: deactivates PK
Fates of G6P (1) and conversion to G1P (3) in Other Pathways
G1P: Gal. metabolism, glycogen synthesis, uronic acid pathway
Fates of G6P in Essential Metabolism (4)
Glc, Pyruvate, Glycogen, Ribose/NADPH
Fates of Pyruvate (4)
1. Reduced to lactate (regen. NAD+)
2. Oxidized in TCA
3. Converted to Ala (GNG and PS)
4. Ethanol (anaerobic conditions)
Ineffective Glycolysis (3)
Impacts cells that do not have mitochondria mostly (RBCs)
Most defects cause hemolytic anemias
PK is mostly affected enzyme
The Brain and Glc (3)
Only Glc can cross BBB.
When starved, brain uses Glc from the liver via GNG.
Can also use ketone bodies (extreme starvation or ketogenic diet) to create b-hydroxybutyrate.
Type 1 Diabetes
Insulin deficiency due to loss of pancreatic beta cells.
Type 2 Diabetes
Insulin resistance that progresses to loss of beta cell function.
Tarui Disease (GSD VII) (6)
1. Deficient in PFK-1
2. Least common GSD
3. Exercised-induced muscle cramps/weakness
4. Hemolytic anemia
5. High bilirubin and jaundice
6. Sx are usually mild
Glucose Stats (1. whole body 2. brain daily 3. present in body fluid 3. from glycogen)
1. 160 g
2. 120 g
3. 20 g
4. 190 g
Direct Glc reserves sufficient for about 1 day.
Locations of Gluconeogenesis (GNG)
Liver, kidney, SI.
Major Precursors for GNG (aside from pyruvate)
Glycerol, Propionate, Alanine, AAs (minus Leu and Lys)
Unique Enzymes for GNG (4)
1. Pyruvate carboxykinase
2. PEP Carboxylase
3. F 1,6-BPhosphatase
4. G 6-Phosphatase
Enzymes from Glycolysis NOT found in GNG (3)
3. Pyruvate kinase
Negative Regulators for Glycolysis (6)
4. G 6-P
5. F 6-P
Positive Regulators for GNG (5)
5. Acetyl CoA
Negative Regulators for GNG (3)
3. F 2,6-BP
Pyruvate Carboxylase (PC)
Mitochondrial enzyme that converts pyruvate to OAA.
Biotin is a cofactor.
Reduces OAA to malate so it can leave the mitochondria. Malate is reoxidized to OAA in cytosol by cytosolic malate DH.
Rate Limiting Step of GNG
Links lactate from anaerobic glycolysis in RBC and exercising muscle to GNG in the liver.
F 1,6-BP Deficiency
D/O of GNG.
Similar to Tarui disease.
Presents in infancy or early childhood.
Von Gierke Disease
Deficiency in G6P.
Unable to release Glc into blood by the liver in GNG and glycolysis.
Mutation in GLUT 2 transporter.
Unable to take up Glc, Fru, and Gal.
Unable to thrive, hepatomegaly, abdominal bloating, rickets.
Conversion of Glc to Fru-Polyol Pathway
Glc reduced to sorbitol by aldose reductase.
Sorbitol oxidized to Fru by Sorbitol DH.
Cells that do not have S DH can swell. Manifests as cataracts, mainly.
HFCS and Obesity
Fru has lower glycemic index than sucrose, BUT is converted easily to fat as it bypasses he rate limiting step of PFK-1.
Types of Galactosemia (2)
1. GALT Deficiency: leads to accumulation of galactitol.
2. Deficiency in Galactokinase: leads to accumulation of Gal and galactitol, causing cataracts early in life.
Overview of PPP
Occurs in cytosol.
Oxidizes G6P ro Ribulose 5-P.
Reduces NADP+ to NADPH (2x)
Produces 1 CO2
Oxidative Phase of PPP (2)
1. G6P DH: RLS. Creates 1 NADPH.
2. NADPH regenrates glutathione (important antioxidant that detoxifies H2O2)
Affects ability to produce NADPH.
Higher incidence in African descent pts.
Presents as hemolytic anemia.
Non-oxidative Phase of PPP
Regenerates Glyceraldehyde 3-P. Shunts product to other pathways (glycolysis, GNG or nucleotide synthesis).
Enzymes in Non-ox Phase of PPP (2)
Transketolase and Transaldolase
Which Cells Have a High Demand for Ribose 5P?
Rapidly dividing cells (needs 5Cs for DNA synthesis
Cells with High Activity of PPP (need NADPH)
Lung, liver, phagocytes.
Non-reducing end of Glycogen
Glc molecule with a free -OH at C4 (terminal Glc).
Protein within glycogen that is connected to the reducing end.
Stored in liver and muscle mostly as granules.
Granules contain all that is needed for glycogen metabolism.
Regulates blood Glc levels.
Reservoir for Glc for physical activity.
3 Key Steps of Glycogenesis
1. Trapping and Activation of Glc
2. Elongation of glycogen primer
3. Branching of gycogen
Trapping and Activation of Glc (3)
1. Hexo/gluco convert Glc to G6P which traps Glc in cell.
2. Phosphoglucomutase reversibly isomerizes G6P to G1P.
3. UDP-glucose pyrophosphorylase transfers G1P to UTP and creates UDP-glucose
Elongation of Glycogen Primer (1)
Glycogen synthase (RL enzyme) catalyzes transfer of UDP-glucose to non-reducing end.
Branching of Glycogen (1)
Glucosyl (4:6) transferase transfers glycogen chains (after about 11 residues (it takes about 7 residues and reattaches elsewhere).
2 Key Steps of Glycogenolysis
1. Chain shortening
2. Branch transfer and release of Glc
Chain Shortening (3)
1. Glycogen phoshorylase (RL enzyme) cleaves at non-reducing end.
2. Pyridoxal phosphate (Vit B6) is a cofactor.
3. Process continues until GP is within 4 residues of an a-1,6 branch point linkage.
Branch Transfer and Release of Glc (2)
1. Debranching enzyme transfers a block of 3 of the 4 remaining Glc to non-reducing end.
2. Enzymes then cleave the a-1,6 bond of the 1 remaining Glc residue.
Fate of Liver G1P
G1P converted to G6P and then to Glc by G6Phosphatase and released into blood.
Fate of Muscle G1P
G6P used to make energy in glycolysis and TCA cycle.
2 Key Enzymes for Glycogen Metabolism
Glycogen synthase: RLS of synthesis
Glycogen phosphorylase: RLS of degredation
BOTH regulated by phophorylation
When is Glycogen Synthase Active?
When is Glycogen Phosphorylase Active?
Defective enzyme: glycogen synthase
Pathway affected: chain elongation
GSD II (Pompe Disease)
Defective enzyme: Acid maltase
Pathway affected: Lysosomal glycogenolysis (release of Glc)
GSD IV (Andersen Disease)
Defective enzyme: Glucosyl (4:6) transferase
Pathway affected: chain branching
GSD V (McArdle Disease)
Defective enzyme: Muscle glycogen phosphorylase
Pathway affected: Glycogenolysis (G1P release)