WEEK 1 (Glycolysis) Flashcards
What is Glucose converted into via Anaerobic Metabolism?
Lactate
What is Glucose converted into via the TCA cycle?
H2O and CO2
What is Glucose converted into via the HMP Shunt?
Ribose and NADPH
What is Glucose converted into via Fatty Acid synthesis pathway?
Fatty Acids
What is Glucose converted into via Glycogenesis?
Glycogen
What are the two types of Glucose entry into cells?
Na+ independent entry and Na+ dependent entry
What is the difference between Na+ independent entry and Na+ dependent entry?
Na+ independent entry:
- 14 different transporters
- Varies by tissue
Na+ dependent entry:
- Glucose is absorbed from low to high concentration
- Occurs in Intestinal epithelium in Renal tubules
What are Sodium-dependent glucose cotransporters?
A family of glucose transporters found in the INTESTINAL MUCOSA of the SMALL INTESTINE and the PROXIMAL TUBULE of the NEPHRON
Describe how Sodium-dependent glucose co-transporters work
An Na+/K+ ATPase pump pumps 3 sodium ions OUTWARD into the blood while BRINGING IN 2 potassium ions which creates a downhill SODIUM ION GRADIENT from the outside to the inside of the proximal tubule cell. The SGLT proteins use the energy from the sodium ion gradient created by ATPase pump to transport glucose across the APICAL MEMBRANE, against an uphill glucose gradient.
What are GLUT 1, GLUT 2, GLUT 3 & GLUT 4?
Na+ independent transporters
Describe GLUT 1
- Found in most tissues (brain, red blood cells)
- 1mM (low Km suggests high affinity so glucose uptake from bloodstream is constant)
- MAIN FUNCTION: Basal uptake of glucose
What does Km mean?
The Km value is an indicator of the affinity of the transporter protein for glucose molecules so a low Km suggests a high affinity
(therefore GLUT1 and GLUT3 have a high affinity for glucose and uptake from the bloodstream is constant)
Describe GLUT 2
- Found in Liver and Pancreatic B-cells
- 15 mM (high Km allows for glucose sensing)
- MAIN FUNCTION: Uptake and release of glucose by the liver B-cell glucose sensor
Describe GLUT 3
- Found in most tissues
- 1 mM (low Km suggests high affinity so glucose uptake from bloodstream is constant)
- MAIN FUNCTION: Basal uptake of glucose
GLUT 4
- Found in skeletal muscle and adipose tissue
- 5mM
- MAIN FUNCTION: Insulin-stimulated glucose uptake and stimulated by exercise in skeletal muscle
What is Glycolysis also called?
Embden-Meyerhof Pathway (EMP)
What happens in Glycolysis?
One molecule of glucose (6 carbon molecule) is degraded into two molecules of pyruvate (3 carbon molecule) & Free energy is released and is stored as 2 molecules of ATP and 2 molecules of NADH
How many enzyme-catalysed reactions occur in glycolysis?
10
Describe the 2 stages of enzyme-catalysed glycolysis
STAGE 1
- A PREPARATORY STAGE
- Glucose is PHOSPHORYLATED, converted to FRUCTOSE which is PHOSPHORYLATED and CLEAVED into two molecules of GLYCERALDEHYDE-3-PHOSPHATE
- 2 molecules of ATP used
STAGE 2
- 2 molecules of GLYCERALDEHYDE-3-PHOSPHATE are converted to PYRUVATE with the formation of 4 ATP molecules and 2 molecules of NADH
What is the net gain of ATP molecules per molecule of Glucose in glycolysis?
There is a net gain of two ATP molecules per molecule of Glucose
Why is 2,3BPG present in erythrocytes in significant amounts?
It regulates oxygen affinity to haemoglobin
What are the properties of Hexokinase?
- Found in most tissues (except liver and pancreatic cells)
- Strongly inhibited by G6P
- Blocks cells from hording glucose
- Insulin = no effect
- Low Km (high affinity for glucose so uptake from bloodstream in constant)
- Low Vm (decreased capacity)
- Gene mutation NOT associated with maturity-onset diabetes of the young
What are the properties of Glucokinase?
- Found in liver and pancreas
- NOT inhibited by G6P
- Induced by insulin
- Insulin = promotes transcription
- Inhibited by F6P
- High Km (decreased affinity for glucose)
- High Vm (increased capacity)
- Gene mutation IS associated with maturity-onset diabetes of the young
What is the function of Glucokinase regulatory protein (GKRP)?
Translocates glucokinase to nucleus which inactivates the enzyme
What is the role of Fructose 6 Phosphate in GKRP?
GKRP binds glucokinase which inactivates the nucleus
What is the role of Glucose in GKRP?
- Competes with GKRP for GK binding
- Glucokinase activates the cytosol
What are the symptoms of Maturity-onset diabetes of the young (MODY)?
- Mild to severe hyperglycaemia
- Impaired glucose-induced secretion of insulin release
What are the properties of Maturity-onset diabetes of the young (MODY)?
- Found in patients <25 years old and are not obese
- May progress into type 2 DM
- Treatment varies with regards to oral hypoglycaemic agents or insulin
What is the function of Glycolysis in Aerobic and Anaerobic respiration?
AEROBIC = To convert glucose to pyruvate and ATP. Pyruvate can be burned for energy (TCA) or converted to fat (Fatty acid synthesis)
ANAEROBIC = ATP production & recycle NADH by making lactate
What is the equation for Glycolysis?
Glucose + 2 ATP = 2 NADH + 4 ATP + 2 Pyruvate
Which enzymes convert Glucose into Glucose-6-Phosphate?
Hexokinase & Glucokinase
How can skeletal muscles degrade protein for energy?
Skeletal muscles produce alanine which is transferred from the blood to the liver. The liver converts alanine to glucose.
What is the function of Alanine Transaminase (ALT)?
Catalyses the reversible transamination between alanine and pyruvate
Which enzymes regulate Glycolysis?
- Hexokinase
- Glucokinase
- Phosphofructokinase-1
- Pyruvate kinase
Describe Pyruvate Kinase Deficiency
Pyruvate Kinase deficiency is the second most common genetic deficiency that causes HAEMOLYTIC ANAEMIA (occurs when you have a low number of red blood cells due to too much hemolysis in the body)
The red blood cell has NO MITOCHONDRIA and is totally dependent on anaerobic glycolysis for ATP. The decrease in ATP causes the ERYTHROCYTE to lose its BICONCAVE SHAPE & decreased ion pumping via Na+/K+ATPase results in loss of ION BALANCE and causes OSMOTIC FRAGILITY leading to SWELLING and LYSIS
SYMPTOMS:
- Chronic haemolysis
- Increased 2,3-BPG resulting in lower-than-normal oxygen affinity of HbA
- Absence of Heinz bodies
What are the properties of 2,3 Biphosphoglycerate?
- Created from diverted 1,3 BPG
- Used by RBCs with no mitochondria or TCA cycle
- Sacrifices ATP from glycolysis
- 2,3 BPG alters Hgb binding
What is the role of Arsenate in Glycolysis?
- Arsenate is chemically similar to phosphate
- Creates 1-arseno-3-phosphoglycerate instead of 1,3-biphosphoglycerate (1,3 BPG)
- 1-arseno-phosphoglycerate is hydrolysed by water to create 3-phosphoglycerate and glycolysis can proceed
- 1 ATP molecule is lost so no net ATP is produced
What is Lactate?
Lactate is formed from pyruvate by Lactate dehydrogenase & is the final product of anaerobic glycolysis in eukaryotic cells
Reduction to lactate is the major fate for pyruvate in which tissues?
Tissues that are poorly vascularised or in RBC that lack mitochondria
What does the direction of the Lactate dehydrogenase reaction depend on?
- Relative intracellular concentrations of pyruvate and lactate
- Ratio of NADH/NAD+
Describe how NADH production results in cramps
1) In exercising skeletal muscle, NADH production exceeds the oxidative capacity of the Electron transport chain which results in an elevated NADH/NAD+ ratio
2) This favours reduction of pyruvate to lactate by LACTATE DEHYDROGENASE
3) Therefore, during intense exercise, lactate accumulates in muscle causing a drop in the INTRACELLULAR pH resulting in CRAMPS
What is Lactic acidosis?
Elevated concentrations of lactate in the plasma (a type of metabolic acidosis)
How does Lactic acidosis occur?
Occurs when there is a collapse of the circulatory system such as MYOCARDIAL INFARCTION, PULMONARY EMBOLISM, UNCONTROLLED HAEMORRHAGE or when an individual is in SHOCK
What happens during Lactic acidosis?
The failure to bring adequate amounts of O2 to the tissues results in IMPAIRED OXIDATIVE PHOSPHORYLATION and DECREASED ATP SYNTHESIS. To survive, the cells rely on anaerobic glycolysis for generating ATP producing LACTIC ACID as the end product
