10 BIOCHEMISTRY
CHAPTER
Glucose Transporters
SGLT GLUT
Sodium and Glucose co-transport Only Glucose transport
Secondary active transport Facilitated transport
Unilateral Bilateral
SGLT 1 : Intestines 1 intestine GLUT 1 and 3 : Basal uptake in crucial organs
SGLT 2 : Kidneys 2 kidneys (Brain, RBCs, Placenta)
GLUT 2 : Food related Max affinity for glucose : GLUT 3
SGLT 2 inhibitors
(Liver, Pancreas, Small intestine)
OHA : Flozins GLUT 4 : Insulin dependent uptake
Risk of UTI, Euglycemic DKA
(Skeletal muscle and adipose tissue)
Used now in heart failure
Substrates
FED STATE : Every organ uses Glucose
except Heart to prevent lactic acid build up, which can affect ion channels.
FASTING STATE (12-18hrs) : Every organ uses Fatty Acids
except RBCs (only glycolysis) and Brain (fatty acids can't cross BBB)
STARVATION (1-3 days) : Every organ uses Ketone bodies
except RBCs (only glycolysis), Liver (lacks Thiophorase, hence uses AMINO ACIDS).
Basics of Metabolism
Anabolic Pathways Catabolic Pathways Sensitive
Occurs in Cytoplasm Occurs in Mitochondria
Insulin mediated (LPL active) Glucagon mediated (HSL active)
Enzymes active in dephosphorylated phase Enzymes active in phosphorylated phase
( CAMP and Protein Kinase A) ( CAMP and Protein Kinase A)
1. All synthesis reactions except KB synthesis 1. Gluco-neo-genesis
2. Glycolysis 2. Glycogen-o-lysis HUG pathways
cytoplasm + mitochondria
3. FA oxidation
1. Heme synthesis
4. KB sythesis and breakdown
2. Urea Cycle
3. Gluconeogenesis
Glycogenolysis is an exception, occurs in cytopalsm
, Trans-Amination
One amino acid to another
Requires Vit B⁶ as cofactor for enzyme amino-transferase
Alanine is the most glucogenic amino acid and forms Cahill cycle
GOT or AST
Oxalo-acetate Aspartate (toAST in OT)
Aspartate transferase or
Glutamate-oxaloacetate transferase
GPT or AST
Pyruvate L-Alanine
Aspartate transferase or
Glutamate-oxaloacetate transferase
, Glycolysis vs Gluconeogenesis
Glucose
Hexokinase Glucose-6-phosphatase
Glucose-6-phosphate
Phosphohexose isomerase Phosphohexose isomerase
Supported by
PFK 2 Fructose-6-phosphate
Fructose 2,6 Phosphofructokinase-1 Fructose-1,6-bisphosphatase
bisphosphate Rate limiting Step
Fructose-1,6-bisphosphate
Inhibited by
Citrate Aldolase Aldolase
Dihydroxyacetone phosphate Dihydroxyacetone phosphate
Glyceraldehyde-3-phosphate (2)
Inhibited by
Arsenic Glyceraldehyde phosphate dehydrogenase Glyceraldehyde phosphate dehydrogenase
Iodoacetate Produces 2 NADH
1,3-bisphosphoglycerate (2)
Phosphoglycerate kinase Phosphoglycerate kinase
3-phosphoglycerate (2)
Phosphoglycerate mutase Phosphoglycerate mutase
2-phosphoglycerate (2)
Inhibited by
Enolase Enolase
NaF
PEP carboxykinase
Phosphoenolpyruvate (2)
Pyruvate kinase Oxaloacetate (2)
Pyruvate (2) Pyruvate carboxylase
Irreversible Steps Pyruvate carboxylase is present in mitochondria
Pyruvate to Oxalo-acetate reaction occurs in
Glycolysis Gluconeogenesis mitochondria and uses ATP
1. Hexokinase/glucokinase 1. Glucose-6-phosphatase Malate-Aspartate shuttle moves Oxalo-acetate from
2. PFK-1 (RLS) 2. Frucrose 1,6 - bisphosphatase inside mitochondria to cytosol for Gluconeogenesis
3. Pyruvate kinase 3. PEP carboxykinase Malate Aspartate shuttle also moves NADH produced
4. PEP carboxylase (in mitochondria) in cytosol to mitochondria
Gluco-kinase vs Hexokinase Substrates for Gluco-neogenesis
1. Hexokinase present in all tissues (low Km and Vmax, which 1. Alanine most glucogenic amino acid (cAhill cycle, alanine
means more affinity for glucose) to pyruvate)
2. Glucokinase present in Liver and B cells (High Km and Vmax 2. Lactate from muscles get converted to pyruvate
which means it has lesser affinity for glucose) (Cori cycle) core muscles training
High on Glucose 3. All TCA intermediate
4. Odd chain Fatty Acids : PMS FuMO
Energetics of Glycolysis Acetyl Co A the strongest initiator of Gluconeogenesis
but can't be a substrate (link reaction is not reversible)
Anaerobic : 4 - 2 = 2
Aerobic : (5 + 4) - 2 = 7
Glycolysis + link rn + TCA : 7 + 5 + 2(10) = 32 Fasting (0-16hrs) : Glycogenolysis
Fasting (16-48hrs) : Gluconeogenesis
Hexikinase and PFK1 consume 1 ATP each.
Glycogenolysis skips hexokinase (6 ATP from aerobic)
Occurs majorly in Liver and Kidney
Phosphoglycero kinase and Pyruvate kinase produce 2 ATP each
In Prolonged fasting : Kidney
CHAPTER
Glucose Transporters
SGLT GLUT
Sodium and Glucose co-transport Only Glucose transport
Secondary active transport Facilitated transport
Unilateral Bilateral
SGLT 1 : Intestines 1 intestine GLUT 1 and 3 : Basal uptake in crucial organs
SGLT 2 : Kidneys 2 kidneys (Brain, RBCs, Placenta)
GLUT 2 : Food related Max affinity for glucose : GLUT 3
SGLT 2 inhibitors
(Liver, Pancreas, Small intestine)
OHA : Flozins GLUT 4 : Insulin dependent uptake
Risk of UTI, Euglycemic DKA
(Skeletal muscle and adipose tissue)
Used now in heart failure
Substrates
FED STATE : Every organ uses Glucose
except Heart to prevent lactic acid build up, which can affect ion channels.
FASTING STATE (12-18hrs) : Every organ uses Fatty Acids
except RBCs (only glycolysis) and Brain (fatty acids can't cross BBB)
STARVATION (1-3 days) : Every organ uses Ketone bodies
except RBCs (only glycolysis), Liver (lacks Thiophorase, hence uses AMINO ACIDS).
Basics of Metabolism
Anabolic Pathways Catabolic Pathways Sensitive
Occurs in Cytoplasm Occurs in Mitochondria
Insulin mediated (LPL active) Glucagon mediated (HSL active)
Enzymes active in dephosphorylated phase Enzymes active in phosphorylated phase
( CAMP and Protein Kinase A) ( CAMP and Protein Kinase A)
1. All synthesis reactions except KB synthesis 1. Gluco-neo-genesis
2. Glycolysis 2. Glycogen-o-lysis HUG pathways
cytoplasm + mitochondria
3. FA oxidation
1. Heme synthesis
4. KB sythesis and breakdown
2. Urea Cycle
3. Gluconeogenesis
Glycogenolysis is an exception, occurs in cytopalsm
, Trans-Amination
One amino acid to another
Requires Vit B⁶ as cofactor for enzyme amino-transferase
Alanine is the most glucogenic amino acid and forms Cahill cycle
GOT or AST
Oxalo-acetate Aspartate (toAST in OT)
Aspartate transferase or
Glutamate-oxaloacetate transferase
GPT or AST
Pyruvate L-Alanine
Aspartate transferase or
Glutamate-oxaloacetate transferase
, Glycolysis vs Gluconeogenesis
Glucose
Hexokinase Glucose-6-phosphatase
Glucose-6-phosphate
Phosphohexose isomerase Phosphohexose isomerase
Supported by
PFK 2 Fructose-6-phosphate
Fructose 2,6 Phosphofructokinase-1 Fructose-1,6-bisphosphatase
bisphosphate Rate limiting Step
Fructose-1,6-bisphosphate
Inhibited by
Citrate Aldolase Aldolase
Dihydroxyacetone phosphate Dihydroxyacetone phosphate
Glyceraldehyde-3-phosphate (2)
Inhibited by
Arsenic Glyceraldehyde phosphate dehydrogenase Glyceraldehyde phosphate dehydrogenase
Iodoacetate Produces 2 NADH
1,3-bisphosphoglycerate (2)
Phosphoglycerate kinase Phosphoglycerate kinase
3-phosphoglycerate (2)
Phosphoglycerate mutase Phosphoglycerate mutase
2-phosphoglycerate (2)
Inhibited by
Enolase Enolase
NaF
PEP carboxykinase
Phosphoenolpyruvate (2)
Pyruvate kinase Oxaloacetate (2)
Pyruvate (2) Pyruvate carboxylase
Irreversible Steps Pyruvate carboxylase is present in mitochondria
Pyruvate to Oxalo-acetate reaction occurs in
Glycolysis Gluconeogenesis mitochondria and uses ATP
1. Hexokinase/glucokinase 1. Glucose-6-phosphatase Malate-Aspartate shuttle moves Oxalo-acetate from
2. PFK-1 (RLS) 2. Frucrose 1,6 - bisphosphatase inside mitochondria to cytosol for Gluconeogenesis
3. Pyruvate kinase 3. PEP carboxykinase Malate Aspartate shuttle also moves NADH produced
4. PEP carboxylase (in mitochondria) in cytosol to mitochondria
Gluco-kinase vs Hexokinase Substrates for Gluco-neogenesis
1. Hexokinase present in all tissues (low Km and Vmax, which 1. Alanine most glucogenic amino acid (cAhill cycle, alanine
means more affinity for glucose) to pyruvate)
2. Glucokinase present in Liver and B cells (High Km and Vmax 2. Lactate from muscles get converted to pyruvate
which means it has lesser affinity for glucose) (Cori cycle) core muscles training
High on Glucose 3. All TCA intermediate
4. Odd chain Fatty Acids : PMS FuMO
Energetics of Glycolysis Acetyl Co A the strongest initiator of Gluconeogenesis
but can't be a substrate (link reaction is not reversible)
Anaerobic : 4 - 2 = 2
Aerobic : (5 + 4) - 2 = 7
Glycolysis + link rn + TCA : 7 + 5 + 2(10) = 32 Fasting (0-16hrs) : Glycogenolysis
Fasting (16-48hrs) : Gluconeogenesis
Hexikinase and PFK1 consume 1 ATP each.
Glycogenolysis skips hexokinase (6 ATP from aerobic)
Occurs majorly in Liver and Kidney
Phosphoglycero kinase and Pyruvate kinase produce 2 ATP each
In Prolonged fasting : Kidney
