Carbohydrate Metabolism Ch.9 Flashcards
GLUT 2
-low affinity transporter in hepatocytes and pancreatic cells (liver and pancreas)
-captures excess glucose after a meal for storage
-when [glucose] drops below the Km for transporter, much of the remainder bypasses the liver and enters peripheral circulation
Km for GLUT2 is high meaning the liver will pick up glucose in proportion to its concentration in the blood - liver will pick up excess glucose and store it after a meal when glucose is high
-GLUT 2 with glucokinase = glucose sensor for insulin release
GLUT 4
- in adipose tissue and muscle and respond to glucose concentration in peripheral blood
- rate of transport increased by insulin that stimulates movement of more GLUT 4 transporters
- Km close to normal glucose (5mM) meaning that the transporter is saturated when blood glucose levels are a bit higher than normal
- cells with GLUT 4 transporters can increase glucose intake by increasing number of GLUT 4 transporters
How does insulin promote glucose entry into the cell?
GlUT 4 levels are satuarated when glucose levels are only slightly above 5mV, so glucose entry can only be increased by increasing the number of transporters. Insulin promotes the fusion of vesicles containing performedGLUT 4 with the cell membrane
Hexokinase
- Function: Phosphorylates glucose to form glucose 6-phosphate, “trapping” glucose in the cell.
- Regulation: Inhibited by glucose-6-phosphate
- Reversible? irreversible
Glucokinase
- Function: Also Phosphorylates and traps glucose in liver and pancreatic cells, and works with GLUT-2 as part of the glucose sensor in beta cells.
- Regulation: In liver cells, it is induced by insulin
- Reversible? Irreversible
Phosphofructokinase (PFK-1)
- Function: Catalyzes the rate limiting step of glycolysis, phosphorylating fructose 6-phosphate to fructose 1,6-bisphosphate using ATP.
- Regulation:Inhibited by ATP, citrate and glucagon. It is activated by AMP, fructose 2,6-bisphosphate and insulin.
- Reversible: Irreversible
Glyceraldehyde-3-phosphate dehydrogenase
- Function: Generate NADH while phosphorylating glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate
- Reversible: Reversible
3-phosphoglycerate kinase
- Function: Performs a substrate-level phosphorylation, transferring a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
- Reversible: Reversible
Pyruvate kinase
- Function: Another substrate-level phosphorylation, transferring a phosphate from phosphoenolpyruvate (PEP) to ADP, forming ATP and pyruvate.
- Regulation:Activated by fructose 1,6- bisphosphate.
- Reversible: irreversible
Why much pyruvate undergo fermentation for glycolysis to continue
Fermentation must occur to regenerate NAD+, which is in limited supply in cells. Fermentation generates NO ATP or energy carriers; it merely regenerates the coenzymes needed for glycolysis
Why is it necessary that fetal hemoglobin does not bind to 2,3-BPG?
The binding og 2,3-BPG decreases hemoglobin’s affinity for oxygen. Fetal hemoglobin must be able to “steal” oxygen from maternal hemoglobin at the placental interference; therefore; it would be disadvantageous to lower its affinity for oxygen.
Fermentation
- lactate dehydrogenase - oxidizes NADH to NAD+ replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate -dehydrogenase (without mitochondria and oxygen, glycolysis would stop when all NAD+ available was reduced to NADH)
- reduces pyruvate to lactate and oxidizes NADH to NAD+ where there is no net loss of carbon because pyruvate and lactate are both 3 carbons
- in yeast cells - conversion of pyruvate (3 carbon) to ethanol (2 carbons) and CO2
- in both the goal is to replenish NAD+
Dihydroxyacetone Phosphate (DHAP)
- used in hepatic and adipose tissue for triacylglycerol synthesis
- formed from fructose 1,6-bisphosphate
- can be isomerized to glycerol 3-phosphate which can be converted to glycerol - backbone of triacylglycerols
1,3 BPG and PEP
high energy intermediates used to generate ATP from substrate level phosphorylation
Irreversible Enzymes in Glycolysis
glucokinase hexokinase PFK-1 pyruvate kinase *how glucose pushes forward the process kinases*
Glycolysis in Erythrocytes - bisphosphoglycerate mutase
- bisphosphoglycerate mutase produces 2,3-BPG from 1,3-BPG in glycolysis
- mutase - moves a functional group from one place to another (phosphate moved from 1 to 2 position)
- 2,3- BPG allosterically binds to β chains of HbA and decreases its affinity for oxygen still allowing 100% saturation in lungs but allows for oxygen unloading in tissues (shifts curve right)
- if too much - may affect saturation
- **2,3-BPG does NOT bind well to HbF so fetus has higher oxygen affinity
RLE (rate limiting enzyme) Glycolysis
phosphofructokinase-1
RLE (rate limiting enzyme) Fermentation
lactate dehydrogenase
RLE (rate limiting enzyme) Glycogenesis
glycogen synthase
RLE (rate limiting enzyme) glycogenolysis
glycogen phosphorylase
RLE (rate limiting enzyme) gluconeogenesis
fructose- 1,6- bisphosphatase
RLE (rate limiting enzyme) pentose phosphate pathway
glucose-6- phosphate dehydrogenase
Which enzymes are responsible for trapping galactose in the cell? What enzyme in galactose metabolism results in a product that can feed directly into glycolysis, linking the two pathways?
Galactose is phosphorylated by galactokinase, trapping it in the cell.
Galactose-1-phosphate uridyltransferase produces glucose 1- phosphate, a glycolytic intermediate, thus linking the pathways.
Which enzymes are responsible for trapping Fructose in the cell? What enzyme in Fructose metabolism results in a product that can feed directly into glycolysis, linking the two pathways?
Fructose is phosphorylated by fructokinase, trapping it in the cell.
Aldolase B produces dihydroxyacetone phosphate (DHAP) and glyceraldehyde (which can be phosphoralated to form glyceraldehyde - 3- hosphate), which are glycolytic intermediates, thus linking the two pathways.
What are the reactants and the products of the pyruvate dehydrogenase complex?
This is an irreversible complex
Reactants:NAD+, CoA, Pyruvate
Products:Acetyl-CoA, NADH+, CO2
How does acetyl-CoA affect PHD complex activity? Why?
Acetyl-CoA inhibits the PHDcomplex. As a product of the enzymes complex, a build up of Acetyl-CoA from either the ccitric acid cycle or fatty acid oxidationsignals that the cell is energetically satisfied and that the production of acetyl-CoA should be slowed or stopped. Pyruvate can then be used to form other products such as, oxaloacetate for use in gluconeogenesis.
What are the 3 fates of pyruvate?
- Conversion to acetyl-CoA by PDH
- Convert to lactate by lactate dehydrogenase
- Convert to oxaloacetate by pyruvate carboxylase
What is the structure of glycogen? What types of glycosidic links exist in a glycogen granule?
Glycogen is made up of a core protein of glycogenin with linear chains of glucose emanating out from the center, connected by alpha-1,4 glycosidic links. Some of these chains are branched, which requires alpha- 1,6 glycosidic links
What are the two main enzymes of glycogenesis, and what does each accomplish?
Glycogen synthase attaches the glucose molecule from UDP-glucose to the growing glycogen chain, forming an alpha-1,4 link in the process. Branching enzyme creates a branch by breaking alpha-1,4 link in the growing chain and moving a block of oligoglucose to another location in the glycogen granule. The oligoglucose is then attached with an alpha-1,6 link.
What are the two main enzymes of glycogenolysis, and what does each accomplish?
Glycogen phosphorylase removes a glucose molecule from glycogen using a phosphate, breaking the alpha 1,4 link and creating glucose 1-phosphate. Debranching enzyme moves all of the glucose from a branch to a longer glycogen chain by breaking an alpha-1,4 link and forming a new alpha-1,4 link to the longer chain. The branch point is left behind; this is removed by breaking the alpha-1,6 link to form a free molecule of glucose.
Under what physiological conditions should the body carry out glucaneogenesis?
Glucaneogenesis occurs when an individual has been fasting for more than 12 hours. To carry out glucaneogenesis, hepatic (and renal) cells must have enough energy to drive the process of glucose creation, which requires sufficient fat stores to undergo beta-oxidation
What are the 4 enzymes unique to glucaneogenesis? Which irreversible glycotic enzymes do they replace?
- Pyruvate carboxylase > pyruvate kinase
- Phosphoenolpyruvate carboxykinase (PEPCK) > Pyruvate kinase
- Fructose - 1,6- bisphosphate > Phosphofructokinase - 1
- Glucose- 6- phosphatase > Glucokinase
How does acetyl-CoA shift metabolism of pyruvate?
Acetyl-CoA inhibits pyruvate dehydrogenase complex while activating pyruvate carboxylase. The net effect is to shift from burning pyruvate in the citric acid cycle to creating a new glucose molecules for the rest of the body. The acetyl-CoA for this regulation comes predominantly from beta-oxidation, not glycolysis.
Phosphatase
Opposite of kinases
-take off phosphate from group
Kinases
Put on a phosphate on a group
Where is glycogen stored?
In liver and muscle
Mutases
Moves a group on a molecule on some other location on that same molecule
Aldolase
Catalyzes aldol clevage
Dehydrogenages
Transfers a hydride (H) group
What are the two major metabolic products of pentose phosphate pathway? (PPP)
- Ribose 5-phosphate
2. NADPH
What are three primary functions of NADPH?
- Lipid biosynthesis
- Bactericidal bleach formation in certain white blood cells
- Maintenance of glutathionine stores to protect against reactive oxygen species
Glutathionine
It is a reducing agent that can help reverse radical formation before damage is done to the cell
