Carb metabolism 1 Flashcards
Glucose transporters
- GLUT1
- low km; high enzyme affinity
- brain, red blood cells
- GLUT2
- high km; low enzyme affinity; no response at normal glucose conc.
- liver and pancreas cells
- GLUT4
- Insulin dependent for extra glucose entry
- low km
- muscles, adipose cells
enzymes of glycolysis
- Hexokinase/ GLucokinase
- Isomerase
- Phosphofructokinase
- Aldolase
- glycerolaldehyde-3-phosphate dehydrogenase
- 3 phosphoglycerate kinase
- Mutase
- Enolase
- Pyruvate Kinase
Hexokinase/ GLucokinase
- Phosphorylate glucose to prevent escape
- Glucokinase is only in liver and pancreas (high Km) (insulin induced)
- Hexokinase is in all cells (low Km) (G6P inhibited)
- Irreversible step
Phosphofructokinase
- Irreversible step
- rate limiting enzyme
- PFK-1 inhibited by citrate, ATP, lack of PFK-2
- Insulin activates PFK-2 but Glucagon inhibits thereby inhibiting PFK-1
Aldolase
- Triose isomerase q
- switches DHAP with GAP
- glycerolaldehyde-3-phosphate dehydrogenase
- produces 1,3-BPG and NADH
- 3 phosphoglycerate kinase
- produces 3-PG
- a type of substrate level phosphorylation where you don’t need oxygen to produce ATP
- Mutase
- Produces 2-PG
- Enolase
- Produces phosphoenolpyruvate and H2O
- Pyruvate Kinase
- Irreversible step
- another substrate level phosphorylation
- stimulated by F-1,6-BP
Fermentation
- produces NAD+ and lactic acid (lactate) or Ethanol
Important Intermediates of Glycolysis
- DHAP: In TAG synthesis, isomerized to glycerol-3-P and used as backbone
- 1,3-BPG and PEP: generates ATP by substrate level phosphorylation
Irreversible enzymes
- Glucokinase or Hexokinase
- Phosphofructokinase-1 (PFK-1)
- Pyruvate Kinase
Rate limiting enzymes
- Phosphofructokinase
- Glycogen synthase
- glycogen phosphorylase
- glucose -6-phosphate dehydrogenase
Substrate level phosphorylation intermediates
- 1,3 bisphosphoglycerate
- Phosphoenolpyruvate
Glycolysis in Erythrocytes
- Only anaerobic glycolysis occurs
production of 2,3-BPG by the enzyme bisphosphoglycerate mutase
↑ 2,3-BPG → decrease oxygen affinity in Hemoglobin A
Galactose Metabolism
- Sourced by Lactose
phosphorylated by Galactokinase
converted to glucose 1 phosphate by galactose-1-phosphate uridyltransferase and an epimerase
Fructose Metabolism
phosphorylated by Fructokinase
cleaved into DHAP and glyceraldehyde by aldolase B
- tHis occurs past the rate-limiting enzyme PFK-1 which means its unregulated
PYRUVATE DEHYDROGENASE
irreversible
converts pyruvate into acetyl-CoA
- Made of 3 enzymes and 5 coenzymes
- 1st enzyme has TPP (Thiamine pyrophosphate)
- 2nd enzyme has CoA and lipoic acid
- 3rd enzyme has NAD and FAD
Glycogen
- liver glycogen is for blood glucose levels
- muscle glycogen is for muscle activity
Glycogenesis
- Begins with the core, glycogenin
Glycogen synthase
- creates 1,4 glycosidic linkages
- stimulated by insulin and G6p
- inhibited by epinephrine and glucagon
Branching enzyme
- Glycosyl 4:6 Transferase
- creates 1,6 glycosidic bonds
- By hydrolyzing a 1,4 linkage
Glycogenolysis
- Glycogen Phosphorylase
- only breaks 1,4 glycosidic bonds
- activated by glucagon in liver
- activated by AMP in muscle- Debranching enzymes (4:4 transferase) then (1,6 Glucosidase)
- Also breaks 1,4 glycosidic bonds but only the ones close to branching point and puts it on the core polymer
- technically breaking a 1,4 bond and making another 1,4 bond
- 1,6 glucosidase breaks the branching point, releasing a free glucose with no phosphate
- Debranching enzymes (4:4 transferase) then (1,6 Glucosidase)
gluconeogenesis
- maintain blood glucose
- stimulated by glucagon and epinephrine
- substrates for this process are Glycerol (after phosphorylation), lactate (lactic acid), alanine
- pyruvate is also known as the ketoacid of alanine because when alanine gives off its amino group, it becomes pyruvate
Gluconeogenesis requires ATP provided from Beta oxidation of fatty acids
- pyruvate is also known as the ketoacid of alanine because when alanine gives off its amino group, it becomes pyruvate
Enzymes that are needed to be reverse gluconeogenesis
- Pyruvate Carboxylase
- Phosphoenolpyruvate carboxykinase
- Fructose-1,6-Bisphosphatase
- Glucose-6-phosphatase
Pyruvate Carboxylase
reversal of pyruvate into PEP
- product is Oxaloacetate
- OAA is metabolized to malate by malate dehydrogenase
- malate is exported from mitochondria
- Then converted back to OAA by malate dehydrogenase
- Stimulated by Acetyl-CoA (after Beta oxidation of fatty acids)
Phosphoenolpyruvate carboxykinase
reversal of pyruvate into PEP
- Product is PEP
- stimulated by glucagon
Fructose-1,6-Bisphosphatase
reversal of F-1,6-BP into F-6-P
- stimulated by ATP
- inhibited by PFK-2 and AMP
Glucose-6-phosphatase
only present in liver not muscle
part of ER membranefacing the lumen
removes phosphate
reversal of glucokinase
PENTOSE PHOSPHATE PATHWAY
produces NADPH
produces pentose sugar (R5P)
- Made of two phases/parts
- oxidative
- produces NADPH
- irreversible/ one way
- rate limiting step is the first enzyme glucose -6-phosphate dehydrogenase
- stimulated by insulin, and NADP+
- inhibited by NADPH
- Nonoxidative
- reversible/ two ways
- produces various sugars; glycolysis intermediates (GAP, F6P, etc)
- enzymes within this phase that allow for reversibility:
- transketolase- uses TPP as cofactor
- transaldolase
NADPH
for reducing detox enzymes( Glutathione (natural antioxidant) reduction),
biosynthesis of Nitric oxide, fatty acids, and cholesterol
R5P
for nucleotide biosynthesis
