Glycolysis And PPP Flashcards
What is the fate of absorbed glucose?
GLUT (facilitated diffusion)
– GLUT 2 – liver
– GLUT 1 and 3 – neurons and brain – GLUT 1 - erythrocytes
– GLUT 4 - adipose tissue and muscle (Insulin- responsive)
How is glucose 6 phosphate formed?
• Glucokinase: liver and pancreatic -cells of pancreas (high Km)
– More active when blood glucose is elevated; ‘Glucose sensor’ • Othertissues–hexokinase(lowKm)
• Glucokinase mutations: Hyperglycemia and MODY-2
– -cells of pancreas cannot respond to high blood glucose levels!!!
What are the fates of glucose 6 phosphate in the liver?
Glycolysis
Glycogenesis
Ribulose 5-P NADPH (PPP)
Give an overview of the pentose phosphate pathway
CYTOSOL
• Glucose 6-phosphate dehydrogenase (key enzyme)
– Does NOT form ATP (energy) • Forms NADPH
– Fatty acid biosynthesis, cholesterol biosynthesis and steroid hormone synthesis in liver, adipocytes and endocrine glands
- Malic enzyme also forms NADPH in these tissues
- Forms Ribose phosphate – purine and pyrimidine synthesis
• Transketolase requires TPP (vitamin B1)
– Thiamine deficiency: Low transketolase activity
What are the functions of glycolysis ?
Generate ATP (energy) in presence or absence of O2 (aerobic and anaerobic) and in presence or absence of mitochondria
• Generates ATP (energy)
• Glycolytic enzymes are present in cytosol
– In brain (fed and fasted state), liver (fed state)
– Tissues that lack mitochondria or hypoxic (Only pathway for energy generation)
– Actively contracting skeletal muscle (Glucose obtained from glycogen or plasma glucose)
Give an overview of the glycolysis phases
Stage 1: energy investment phase( glucose to fructose 1,6-bisphosphate)
Stage 2: cleavage of 6C sugar into 3C intermediates (fructose 1,6 biphosphate splits to glyceraldehyde 3 phosphate and dihydroxyacetoje phosphate
Stage 3 energy generation phase
Each glyceraldehyde 3 phosphate and DHA phosphate is used to form pyruvate
2 ATP formed and NADH formed
How does Acetyl CoA enters the mitochondria?
Via shuttle systems
Describe the ATP formed substrate level phosphorylation
• Directly form ATP from ADP
• DO NOT require Electron Transportchainor
mitochondria or Oxygen
- ONLY reactions that form ATP in cells that lack mitochondria and in hypoxic conditions
- High energy compounds – 1,3-Bisphosphoglycerate – Phosphoenolpyruvate
What are the fates of Pyruvate ?
Aerobic- forms Acetyl CoA (Pyruvate dehydrogenase complex-requires TPP and is a mitochondrial enzyme)—> enters TCA cycle
Anaerobic- Anaerobjc-lactate (lactate dehydrogenase and is a cytosolic enzyme)—> goes to liver via Cori cycle
What situations call for anaerobic use of Pyruvate?
Absence of mitochondria (red blood cells, lens, cornea, leukocytes)
Poorly vascularized tissues or hypoxia (contracting skeletal muscle, cardiac muscle hypoxia)
Pyruvate dehydrogenase deficiency or thiamine deficiency
Explain the anaerobic fate of Pyruvate
• NADHformedbyglyceraldehyde3-phosphate dehydrogenase is reoxidized to form NAD+
– Allows glycolysis to proceed in absence of mitochondria
• LDH is cytosolic enzyme
• Direction of reaction: NADH/NAD+ ratio
– Higher NADH, increases lactate
- Identify states of high NADH/NAD+ ratio
- Contrast between muscle (fast-twitch) and liver
Describe the energetics of aerobic glycolysis
- Overall reaction: Glucose→2 Pyruvate
- 2 NADH+ H+ (glyceraldehyde 3-phosphate dehydrogenase) = 2x3 = 6ATP
- (1 NADH=2.5 ATP and 1 FADH2=1.5 ATP; Approximate 1 NADH = 3 ATP and 1 FADH2 = 2 ATP)
- NADH in cytosol by glycolysis transported into mitochondria by shuttle systems (malate-aspartate or glycerol-phosphate shuttle) – Refer Shuttles and OxPhos
- 4 ATP (substrate level phosphorylation) (2ATP from a glyceraldehyde 3-phosphate)
- -2ATP used
- Total = 8 ATP
Describe the energetics of glycolysis under anaerobic conditions
- OverallreactionGlucose→2 Lactate
- 2 NADH+ H+ (glyceraldehyde 3- phosphate dehydrogenase) used in lactate dehydrogenase
- 4ATP(substratelevel phosphorylation) (2ATP from a glyceraldehyde 3-phosphate)
- -2ATPused
- Total = 2 ATP
Describe lactate formation during anaerobic exercise in muscle
• Lactate threshold and endurance training:
Weight loss advice
– 60-70% of maximum heart rate: Fat oxidation by
muscle
– 80-85% of MHR: Anaerobic oxidation forms
lactate
• Anaerobic (strenuous) activity, blood lactate
levels increase
– Lactate in muscle → pH drops and cramps
What are the major comparisons of aerobic exercise?
• Oxygen present
• Glycogenolysis is active and may last
hours
• Glycolysis is active
• Kreb’s cycle and electron transport
chain are both active, producing ample ATP; Oxygen is the final electron acceptor.
- Fatty acid oxidation
- ATP production is maximal