Carb Metabolism Flashcards
salivary amylase
breaks down 1,4 linkages in complex carbs
pancreatic amylase
breaks down 1,6 linkages in complex carbs
sodium-dependent glucose transporter (SGLT1)
uses secondary active transport to move one Na+ and one glucose from the intestinal lumen into enterocytes
glucose transporter (GLUT 2)
transports glucose from enterocyte into blood by facilitated diffusion down its concentration gradient
sodium-potassium ATPase
actively transports 3 Na+ out of the cell (into blood) and 2 K+ into the cell to establish low intracellular Na+ concentration using ATP
hexokinase/glucokinase
make glucose-6-phosphate (in glycolysis)
phosphofructokinase-1
the first rate-controlling enzyme of glycolysis; produces the first committed metabolite (FRU-1,6-BP)
fructose-1,6-bisphosphate
the first committed metabolite in glycolysis; gets split into G3P and DHAP
stage 2 of glycolysis
uses G3P to create high energy phosphates on 3-C intermediates; these phosphates are then transferred to ADP (substrate-level phosphorylation)
substrate level phosphorylation
phosphoglycerate kinase and pyruvate kinase transfer a high-energy phosphate directly from one compound to ATP
*during stage 2 of glycolysis
glyceraldehyde-3-phosphate
the “parent” for the 3-carbon phosphorylated compounds that will support substrate-level phosphorylation of ADP to ATP
net effect of glycolytic pathway
2 NADH molecules and 2 ATP (we used 2 and made four so net = 2)
pyruvate kinase
converts PEP to pyruvate, in the process making ATP via substrate-level phosphorylation
glucokinase
found mainly in the liver and pancreas
-high Vmax
-larger Km (lower affinity for substrate)
hexokinase
found in all cells
-low Vmax (slower)
-smaller Km (high affinity for substrate)
negative regulators of PFK-1
ATP
citrate
low pH (lactic acid)
positive regulators of PFK-1
AMP
ADP
Pi
fructose-2,6-bisphosphate
positive regulators of pyruvate kinase
fructose-1,6-bisphosphate
negative regulators of pyruvate kinase
alanine
acetyl-CoA
ATP
how does cAMP/PKA affect pyruvate kinase?
phosphorylates pyruvate kinase, which INACTIVATES the enzyme
fate of pyruvate - anaerobic glycolysis
lactate dehydrogenase (LDH) converts pyruvate to lactate, oxidizing NADH to NAD+, in the absence of O2
-occurs in cytosol
fate of pyruvate - aerobic glycolysis
pyruvate is shuttled into the mitochondria, interacting with pyruvate dehydrogenase and coenzyme A to form Acetyl-CoA and NADH; requires thiamine
pyruvate dehydrogenase
3 subunits (E1, E2, E3); requires thiamine and makes 1 NADH molecule in the process of converting pyruvate to acetyl-CoA
citrate synthase (TCA cycle)
combines oxaloacetate and acetyl-CoA to make citrate
isocitrate dehydrogenase (TCA cycle)
converts isocitrate to a-ketoglutarate
*requires thiamine (B1)
*loses a CO2
*makes NADH
a-ketoglutarate dehydrogenase (TCA cycle)
converts a-ketogluarate to succinyl-CoA
*requires thiamine (B1)
*makes NADH
TCA cycle overview
uses acetyl-CoA to make 3 NADH and 1 FADH2, which will be used in the ETC to make ATP
-also makes GTP
negative effectors of pyruvate dehydrogenase
-ATP
-acetyl-CoA
-NADH
positive effectors of pyruvate dehydrogenase
-calcium
-ADP
-substrate levels
TCA cycle is regulated by availability of
oxaloacetate and acetyl-CoA
negative regulator molecules of citrate synthase (TCA cycle)
ATP, NADH, succinyl-CoA, citrate
positive regulators of citrate synthase (TCA cycle)
ADP, oxaloacetate
negative regulators of isocitrate dehydrogenase (TCA cycle)
ATP, NADH
positive regulators of isocitrate dehydrogenase (TCA cycle)
Ca2+, ADP
negative regulators of a-ketoglutarate dehydrogenase (TCA cycle)
succinyl-CoA, NADH
positive regulators of a-ketoglutarate dehydrogenase (TCA cycle)
Ca2+
purposes of malate-aspartate shuttle
- keeps conversion of glucose to pyruvate going by maintaining NAD+ levels
- provides some ATP via NADH to ETC
glucose-6-phosphate dehydrogenase (G6PD)
rate-limiting enzyme for the pentose phosphate pathway
pentose phosphate pathway
*yields NADPH!!
-also forms glycolytic intermediates (2 fructose-6-phosphates and 1 glyceraldehyde-3-phosphate)
RATE-LIMITING ENZYME = glucose-6-phosphate dehydrogenase (G6PD)
NADPH is required for
*SYNTHESIS of fatty acids, cholesterol, neurotransmitters, and nucleotides
*DETOXIFICATION of oxidized glutathione and cytochrome P450 monooxygenases (protection against ROS)
how does G6PD deficiency cause anemia?
in G6PD deficiency, we cannot make enough NADPH, which is necessary for producing reduced glutathione (GSH), which is necessary for glutathione peroxidase to convert hydrogen peroxide to water; this causes accumulation of ROS and damages RBC membranes, leading to hemolytic anemia
stimulation of insulin secretion
increased levels of glucose, amino acids, and fatty acids (well-fed conditions) causes insulin release from beta cells in pancreas
stimulation of glucagon secretion
LOW INSULIN levels trigger glucagon secretion
-low insulin levels occur in under-fed conditions
disorders of glycogen metabolism
- Von Gierke (type I)
- Pompe (type II)
Von Gierke disease
defective glucose-6-phosphatase or transport system (can’t get glycogen OUT of liver) -> enlarged liver, severe hypoglycemia, ketosis, hyperuricemia
Pompe disease
defective 1,4-glucosidase (can’t BREAK glycosidic bonds) -> buildup of glycogen in lysosome -> cardiorespiratory failure causes death, usually before the age of 2
glycogen structure
highly branched, with 1,4 and 1,6 linkages
-tens of thousands of glucose residues incorporated into a single glycogen molecule
glycogen synthesis
1) glycogenin has built-in glycogen synthase, which makes the primer
2) glycogen synthase makes 1,4 glycosidic bonds and uses UDP-glucose; elongation of glycogen molecule
3) amylo-1,4-transglycosylase adds in the 1,6 branches
glycogenolysis (breakdown of glycogen)
1) glycogen phosphorylase breaks 1,4 glycosidic bonds, making GLU-6-P
2) in the liver, GLU-6-P is acted on by glucose-6-phosphatase, which removes the phosphate and forms free glucose
3) debranching enzymes break the 1,6 branches
4) free glucose is transported into the blood to maintain euglycemia
effect of glucagon on glycogen metabolism
glucagon turns on glycogen phosphorylase, causing BREAKDOWN of glycogen
effect of insulin on glycogen metabolism
insulin stimulates glycogen synthase, causing FORMATION of glycogen
what is the rate-limiting enzyme for gluconeogenesis
fructose-1,6-bisphosphate phosphatase (PEP-carboxykinase also important)
how is the pyruvate kinase step of gluconeogenesis reversed
1) amino acids and lactate are converted to pyruvate
2) pyruvate carboxylase adds 1 CO2 and consumes 1 ATP to form oxaloacetate
3) PEP-carboxykinase removes a CO2 and uses GTP to add a phosphate and make PEP
how is the phosphofructokinase 1 step reversed in gluconeogenesis
fructose-1,6-bisphosphate phosphatase converts FRU-1,6-BP to FRU-6-P
how is the hexokinase step reversed in gluconeogenesis
glucose-6-phosphatase removes the phosphate from GLU-6-P to produce free glucose
describe the structure of an N-linked glycoprotein
glucose linked to a protein by way of a nitrogen linkage (bound to asparagine)
inclusion cell disease
a defect in glycoprotein carbohydrate recognition signals that there is a failure to phosphorylate mannose residues; the lysosome can’t function so it gets a buildup of material
building N-linked glycoproteins
1) requires dolichol and adds monosaccharides to the dolichol carrier to create “high mannose content” chain
2) transfer high mannose oligosaccharide to a protein destined to be a mature N-linked glycoprotein
3) trim the oligosaccharide and add additional sugars to make a complex chain
4) completed N-linked protein
mucopolysaccharidoses
- lysosomal storage disorder
- deficiency in GAG degradative enzymes
- lysosomal accumulation of GAG products cause dysfunction
-s/s can include organomegaly, vision problems, etc
degradation of proteoglycans
- extracellular proteases fragment in the proteoglycan and the fragments are gathered in coated pits
- enzymes cleave internal glycosidic bonds of GAG, creating smaller fragments
- GAG fragments are degraded to individual monosaccharides in lysosome
