Flashcards in Carbohydrate Metabolism Deck (45):
Ubiquitous but high in RBCs and Brain, Km 1mM
Liver and Pancreas, Km 10mM
Neurons, Km 1mM
INSULIN DEPENDENT, skeletal muscle, adipose tissue, and heart, Km 5mM. Insulin signaling causes fusion of vesicles with plasma membrane and enables glucose uptake.
Net Yield of Glycolysis
2 ATP, 2 NADH, and 2 pyruvate
Irreversible Steps of Glycolysis
Hexokinase/Glucokinase, Phosphofructokinase 1, Pyruvate Kinase
Steps that require ATP for Glycolysis
Glucose -> Glucose-6-Phosphate
Fructose-6-Phosphate -> Fructose-1,6-bisphosphate
Steps that generate NADH for glycolysis
Glyceraldehyde 3-phosphate + NAD+ -> 1,3-bisphosphoglycerate + NADH X 2 via G3P dehydrogenase
Steps that generate ATP for Glycolysis
1,3 bisphosphoglycerate -> 3 phosphoglycerate + ATP X 2
Phosphoenolpyruvate -> Pyruvate X 2
Rate Limiting Enzyme of Glycolysis and explain
Phosphofructose Kinase 1, Insulin activates Protein phosphatase to dephosphorylate PFK-2. Activated PFK-2 can then convert F6P to F-2,6-BP, which can then activate PFK1 to convert F6P to F-1,6-BP.
Regulation of Pyruvate Kinase
Insulin activates protein phosphatases that dephosphorylates PK to activate it. Also activated by F-1,6-BP and insulin and is inhibited by ATP, Alanine, and glucagon. High glucagon and high cAMP activate protein kinase A, that phosphorylated PK to inactivate it.
RBCs and Glycolysis disorders
Since RBCs lack mitochondria, glycolysis is only mechanism for producing ATP. Failure of glycolysis results in ATP deficiency and leads to destruction of RBCs aka hemolytic anemia.
Brain and Glucose relationship
Glucose is one of the only fuel molecule that can cross blood brain barrier. During starvation, brain cells obtain glucose from liver via gluconeogenesis. The brain can also utilize ketone bodies for fuel during excessive starvation.
Carbohydrate metabolism in fed vs fasting state
Fed state: abundant glucose, release of insulin causes glucose uptake by hexokinase/glucokinase and prodction of glycogen and decreased gluconeogenesis. Fasting state: low glucose, release of glucagon and epinephrine. increase on gluconeogenesis and glyocogenolysis.
Characterized by hyperglycemia. Type 1: severe insulin deficiency due to loss of pancreatic beta cells from autoimmune destruction.
Type 2: insulin resistance that progresses to loss of beta cells function
Results from premature destruction of RBCs from causes such as defects in glycolytic enzymes such as phosphoglucose isomerase, triosephosphate isomerase, and pyruvate kinase (most common).
Tarui disease, deficiency in PFK-1 results in exercise-induced muscle cramps, hemolytic anemia, etc.
Whole body needs of glucose daily?
Daily glucose requirement for brain?
Glucose present in bodily fluids?
Glucose readily available from glycogen?
Where does gluconeogenesis occur?
Liver, kidney, and small intestine
Irreversible steps of gluconeogenesis? Activators and inhibitors of each enzyme
Pyruvate -> OAA (Malate OAA shuttle) via pyruvate carboxylase (in mitochondria). Acetyl CoA activates and ADP inhibits.
OAA -> PEP via PEP carboxykinase. Activated by cortisol, glucagon, and thyroxine.
F-1,6,BP -> F6P via F-1,6-bisphosphatase (rate limiting step). Glucagon activates PKA, which phosphorylates PFK2 to inhibit it and stimulates FBPase2 to convert F26BP back to F6P.
Glucose 6P -> Glucose 6 phosphatase.
Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver
Precursors of Gluconeogenesis, sources, and point of entry for each
Glycerol, lipid degradation, and DHAP
Propionate, degradation of odd-numbered FA, TCA cycle
Alanine, protein degradation, pyruvate
AA, protein degradation, TCA cycle intermediates
Disorders of Gluconeogenesis
F1,6BP deficiency developed from mutation in this enzyme. Presents in infancy or early childhood
Von Gierke Disease (autosomal recessive): Deficiency in G6P, patients exhibit marked fasting hypoglycemis, lactic acid
Fructose uptake is via what transporter?
Galactose/Glucose uptake via what?
Inherited deficiency of GLUT2 in the liver, pancreatic beta cells, and PCT. Unable to take up glucose, fructose, and galactose.
Sorbitol accumulation defect
Glucose is reduced to sorbitol by aldose reductase.
Sorbitol oxidized to fructose by sorbitol dehydrogenase
Cells that lack sorbitol dehydrogenase can accumulate sorbitol, which triggers water influx and cause swelling. Manifests as retinopathy and cataracts.
Fructose entry points into glycolysis
Fructose can be converted to F6P and enter straight away of it can be converted to F1P and then glyceraldehyde, which can go to G3P and DHAP. High fructose corn syrup is bad because fructose can bypass PFK1
Deficiency in glucose 1P uridyltransferase (GALT), leads to accumulation of galactitol.
Deficiency in galactokinase, can lead to cataracts in early infancy.
Oxidative steps of PPP
G6P -> Ribulose 5 P and creates 2 NADPH molecules. Rate limiting step is G6P dehydrogenase. G6PD deficiency can cause hemolytic anemia and NADPH is important for phagocytic cells for antioxidant power of glutathione reductase.
Non oxidative Phase of PPP
Generates Ribose-5P , G3P, and fructose 6P
Which cells require a high demand of ribose 5P?
Which cells require a high demand for NADH?
Rapidly dividing cells need ribulose 5P for RNA synthesis
Phagocytic cells require PPP due to NADPH for antioxidants.
Structure of glycogen
Glucose molecules linked together via a(1,4)-glycosidic bond and branch points formed via a-1,6 glycosidic bonds. Non reducing ends have free OH group at C4 and reducing ends are connected to glycogenin.
Where is glycogen stored?
Difference between liver and muscle glycogen?
Glycogen stored in liver, muscle, and other tissues and stored as granules.
Liver Glycogen - regulates blood glucose levels
Muscle glycogen - provides reservoir of fuel for physical activity.
Rate limiting step for Glycogenesis?
Glycogen synthase, which catalyzes the transfer of glucose from UDP-glucose to non-reducing end via a-1,4 glycosidic bond.
Branching enzyme of Glycogenesis?
When glycogen reaches around 11 residues, glucosyl (4:6) transferase reaches monomers a-1,6 bond.
Rate limiting step for Glycogenolysis?
Chain shortening done by glycogen phosphorylase (GP), which reduces glucose-1-P from the non-reducing ends of glycogen. Uses pyridoxal phosphate (Vitamin B6) as cofactor.
Debranching transfer enzyme for glycogenolysis?
transferase (4:4) activity to transfer a block of 3 of the remaining 4 glucose to the non reducing end forming an a-1,4-bond. Then it cleaves the a-1,6 bond of the single remaining glucose.
Pompe disease, deficiency in enzyme a-1,6 glucosidase (acid maltase) -> won't be able to release terminal glucose and break down of glycogen would not be possible.
Activated forms of Glycogen synthase and Glycogen phosphorylase? Inactive form?
When both are P = GS is inactive and GP is active
When both are deP = GS is active and GP is inactive
Glucagon does NOT act on what?
4 key proteins involved in regulation of insulin?
GLUT4, PKB, PP1, and GSK3
Type 2 Diabetes
reduced sensitivity to insulin
Blood glucose criteria : >126 mg/dl fasting or >199 mg/dl fed
Keys enzymes and second messengers affected by glucagon?
G Protein, AC and cAMP, PKA, PP1, PK