ch 9- Carbohydrate Metabolism I Flashcards
GLUT 2
a low affinity transporter in hepatocytes and pancreatic cells; after a meal, blood travelling through the hepatic portal vein from the intestine is rich in glucose which GLUT 2 the excess of for storage. K sub m of GLUT 2 is high - about 15mM
GLUT 4
in adipose tissue and muscles and responds to glucose conc in peripheral blood; K sub m is similar to normal glucose level in blood - about 5 mM
Glycolysis
a cytoplasmic pathway that converts glucose into two pyruvate molecules, releasing a modest amount of energy captured in 2 substrate-level phophorylations and one oxidation reaction; energy carriers produced are NADH and can feed aerobic respiration pathway to generate energy for cell; not carrying out is incompatible with life
Hexokinase
widely distributed enzyme in tissues used during glycolysis; phosphorylates glucose to form glucose 6-phosphate, trapping glucose in the cell, and is inhibited by its product. low K sub m - reaches max velocity at low glucose conc; irreversible
Glucokinase
Glycolysis - enzyme found only in liver cells and pancreatic beta-islet cells where it traps and phosphorylates glucose; in the liver it is induced by insulin. Acts as the glucose sensor along with GLUT 2; high K sub m; irreversible
Phosphofructokinase-1 (PFK-1)
rate-limiting enzyme for glycolysis and main control point in glycolysis. Fructose 6-phosphate is phophorylated to fructose 1,6-bisphosphate using ATP; inhibited by ATP and citrate and activated by AMP, fructose 2,6 bisphosphate and insulin. Insulin stimulates and glucagon inhibits in hepatocytes; irreversible
Phosphofructokinase-2 (PFK-2)
Glycolysis - activated by insulin, inhibited by glucagon. converts a tiny amount of fructose 6-phosphate to fructose 2,6 bisphosphate (F2,6-BP) which activates PFK-1. found mostly in the liver.
lactate dehydrogenase
rate limiting enzyme for fermentation; key fermentation enzyme in mammalian cells; oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phsphate dehydrogenase; prevents glycolysis from stopping when all available NAD+ is reduced to NADH.
glycogen synthase
rate limiting enzyme for glycogenesis
gylcogen phophorylase
rate limiting enzyme for glycogenolysis
fructose 1,6-bisphosphatase
rate limiting enzyme for gluconeogenesis
Glucose-6-phosphate dehydrogenase
rate limiting enzyme for pentose phosphate pathway
reduction and oxidation in biomolecules
oxidation is increasing bonds to oxygen or other heteroatoms (atoms besides C and H); and reduction is increasing bonds to hydrogen
Glyceraldehyde-3-Phosphate Dehydrogenase
enzyme during glycolysis that catalyzes an oxidation and addition of inorganic phosphate (P sub i) to its substrate, glyceraldehyde 3-phosphate resulting in production of high energy intermediate 1,3-bisphosphoglycerate and the reduction of NAD+ to NADH; reversible
3-Phosphoglycerate kinase
performs substrate level phosphorylations; enzyme during glycolysis that transfers high-energy phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate; reversible
substrate-level phosphorylations
reaction that directly phosphorylates ADP to ATP using high-energy intermediate; an example of an enzyme that causes this is 3-Phosphoglycerate kinase; not dependent on oxygen and are the only means of ATP generation in an anaerobic tissue
Pyruvate Kinase
last enzyme in aerobic glycolysis; catalyzes a substrate-level phosphorylation of ADP using the high energy substrate phosphoenolpyruvate (PEP); activated by fructose 1,6-bisphosphate from the PFK-1 reaction. Irreversible
feed-forward activation of pyruvate kinase
the product of an earlier reaction of glycolysis (fructose 1,6-bisphosphate) stimulates, or prepares a later reaction in glycolysis (by activating pyruvate kinase)
Dihydroxyacetone phosphate (DHAP)
intermediate of glycolysis - used in haptic and adipose tissue for triacylglycerol synthesis. formed from fructose 1,6-bisphosphate, can be isomerized to glycerol 3-phosphate which can then be converted to glycerol, the backbone of tracylglycerols
1,3-Bisphosphoglycerate (1,3 BPG) and phosphoenolpyruvate
other intermediates of glycolysis - high energy, used to generate ATP by substrate level phosphorylation. This is the only ATP gained in anaerobic respiration
Irreversible enzymes in glycolysis pathway
keeps pathway moving in one direction; Glucokinase or hexokinase, PFK-1, and pyruvate kinase catalyze reactions that are irreversible
glycolysis in erythrocytes
anaerobic glycolysis is only pathway for ATP production yielding a net 2 ATP per glucose
bisphosphoglycerate mutase
found in RBCs (erythrocytes) - produces 2,3-bisphosphoglycerate (2,3-BPG) from 1,3 BPG in glycolysis; mutases are enzymes that move a functional group from one place in a molecule to another. In this case phosphate is moved from 1 to 2 position
2,3 bisphosphoglycerate (2,3 BPG)
produced from 1,3 BPG; binds allosterically to the beta chains of hemoglobin A (HbA) and decreases its affinity for oxygen; abnormal increase in this may shift the curve far enough so that HbA is not fully saturated in the lungs; does not bind well to fetal Hemoglobin (HbF). therefore this has higher affinity for oxygen
physiological changes that promote a right shift of oxygen dissociation curve (Bohr effect)
high 2,3 BPG, low pH, High [H+], high pCO2. All occur during exercise (exercise is the RIGHT thing to do)
galactose
important monosaccharide; important source is disaccharide lactose which is hydrolyzed to galactose and glucose by lactase, a brush border enzyme of the duodenum; reaches liver through the hepatic portal vein
galactokinase
phosphorylates galactose in the liver, trapping it in the cell
galactose-1-phosphate uridyltransferase
works with an epimerase to convert galactose 1-phosphate from phosphorylated galactose into glucose 1-phosphate
epimerases
enzymes that catalyze the conversion of one sugar epimer to another (epimers are diastereomers that differ at exactly one chiral carbon)
Fructose and fructose metabolism pathway
important monosaccharide (not as important as glucose); found in honey and fruit and part of the disaccharide sucrose (table sugar). Sucrose is hydrolyzed by the duodenal brush border enzyme sucrase to glucose and fructose which are absorbed in hepatic portal vein. liver phosphorylates fructose using fructokinase and traps it. frutose 1-phosphate is then cleaved into glyceraldehyde and DHAP by aldolase B
pyruvate deydrogenase complex (PDH) reaction
pyruvate from aerobic glycolysis is converted to acetyl CoA in the mitochondria for entry into the citric acid cycle if ATP is needed or for fatty acid synthesis if ATP is not needed; irreversible; activated by insulin in the liver but is unresponsive to hormones in nervous system. pyruvate dehydrogenase is inhibited by its product, acetyl CoA and when there is enough acetyl CoA it is instead converted into oxaloacetate to enter gluconeogenesis
Glycogen
branched polymer of glucose; storage form of glucose. core protein of glycogenin with linear chains of glucose emanating out. Synthesis and degradation occur primarily in liver and skeletal muscle. Stored in cytoplasm as granules composed of polyglucose chains. if chains are branched, the glucose density is highest at the periphery allowing more rapid release of glucose on demand. in liver prevents low blood sugar between meals, in muscles energy reserve for muscle contraction
glycogenesis
synthesis of glycogen granules; begins with core protein called glycogenin. Glucose addition to granule through glucose 6-phosphate, then converted to glucose 1-phosphate, which is then activated by coupling to a molecule of uridine diphosphate (UDP), which them permits its integration into the glycogen chain by glycogen synthase. Activation occurs when glucose 1-phosphate interacts with uridine triphosphate (UTP), forming UDP-glucose and pyrophosphate (PP sub i)
glycogen synthase
rate limiting enzyme of glycogen synthesis; also forms the alpha-1,4 glycosidic bond found in linear glucose chains of the granule. Stimulated by glucose 6-phosphate and insulin, inhibited by epi and glucagon through a protein kinase cascade that phophorylates and inactivates the enzyme
Branching enzyme
glycogenesis - responsible for introducing alpha-1,6-linked branches into the granule as it grows; also hydrolyzes one of the alpha-1,4 bonds to release a block of oligoglucose which is then moved and added in a lightly different location; also forms an alpha-1,6 bond to create a branch.
alpha-1,4 keeps the same branch moving 4ward. alpha 1,6 puts a branch in the mix
Glycogenolysis
process of breaking down glycogen
glycogen phosphorylase
rate limiting enzyme of glycogenolysis; phosphorylases break bonds using an inorganic phosphate instead of water; breaks alpha-1,4 glycosidic bonds, releasing glucose 1-phosphate from the periphery of the grandule. cannot break alpha-1,6 bonds. Actived by glucagon in the liver and AMP and epi in skeletal muscle. Inhibited by ATP
Debranching Enzyme
in glycogenolysis - a two-enzyme complex that deconstructs the branches in glycogen that have been exposed by glycogen phosphorylase;
- It breaks an alpha-1,4 bond adjacent to the branch point and moves the small oligoglucose chain that is released to the exposed end of the other chain.
- It forms a new alpha-1,4 bond
- It hydrolyzes the alpha-1,6-bond, releasing the single residue at the branch point as free glucose which represents only free glucose produced directly in glycogenolysis
Isoforms
slightly different versions of the same protein
gluconeogenesis
liver carries out and kidneys on a smaller level; produces acetyl-CoA from beta oxidation of fatty acids; starts with glucose; most steps represent a reversal of glycolysis. stimulated by glucagon lowering F2,6-BP and inhibited by insulin increasing F2,6-BP
Important substrates for gluconeogenesis
glycerol 3-phosphate (from stored fats, or triacylglycerols, in adipose tissue); lactate (from anaerobic glycolysis); and glucogenic amino acids (from muscle proteins)
glucogenic amino acids
all except leucine and lysine - can be converted into intermediates that feed into gluconeogenesis
ketogenic amino acids
can be converted into ketone bodies, which can be used as alternative fuel
pyruvate carboxylase
gluconeogenesis - one of the important enzymes required to catalyze rxns that circumvent irreversible steps of glycolysis. a mitochondrial enzyme that is activated by acetyl-CoA (from beta-oxidation). Product is oxaloacetate (OAA) - citric acid cycle intermediate which cannot leave the mitochondrion so it is reduced to malate which can which is then reoxidized back to OAA. replaces pyruvate kinase
Phosphoenolpyruvate Carboxykinase (PEPCK)
important enzyme in gluconeogenesis. induced by glucagon and cortisol which generally act to raise blood sugar levels; converts OAA to PEP in a rxn that requires GTP. Combination of this and pyruvate carboxylase is used to circumvent the action of pyruvate kinase by converting pyruvate back into PEP
Fructose-1,6-Bisphosphatase
important enzyme in gluconeogenesis. in cytoplasm, key control point of gluconeogenesis, represents rate-limiting step of the process. Reverses action of phosphofructokinase-1 (rate limiting step of glycolysis) by removing phosphate from fructose 1,6-bisphosphate to produce fructose 6-phosphate. activated ATP and inhibited by AMP and fructose 2,6-bisphosphate.
What opposes kinases
phosphatases
Glucose-6-phosphatase
important enzyme in gluconeogenesis; found only in the lumen of the ER in liver cells; used to circumvent glucokinase and hexokinase which convert glucose to glucose-6-phosphate
four important enzymes for gluconeogenesis and what irreversible glycolytic enzymes they replace
pyruvate carboxylase replaces pyruvate kinase; phosphoenolpyruvate carboxykinase (PEPCK) replaces pyruvate kinase; Fructose-1,6-bisphosphatase replaces phosphofructokinase-1, glucose-6-phosphatase replaces glucokinase
pentose phosphate pathway (PPP)
also called hexose monophosphate (HMP) shunt; occurs in cytoplasm of all cells. Two functions: production of NADPH and serving as a source of ribose 5-phosphate for nucleotide synthesis; first part begins with glucose 6-phosphate, ends with ribulose 5-phosphate and is irreversible; produces ribulose 5-phosphate which is isomerized to ribose 5-phosphate, the backbone of nucleic acids
glucose-6-phosphate dehydrogenase (G6PD)
important rate-limiting enzyme of PPP
functions of NADPH
primarily e- donor in many biochemical reactions; reducing agent which is oxidized in the process; cells require it for biosynthesis, mainly of fatty acids and cholesterol, assisting in cellular bleach production in certain WBCs which contributes to bactericidal activity, maintenance of a supply of reduced glutathione to protect against reactive oxygen species (acting as the body’s natural antioxidant)
Glutathione
reducing agent that can help reverse radical formation before damage is done to the cell
