Metabolism Flashcards
Glucose utilization
(1) Storage: glycogen, starch, sucrose
(2) Oxidation: by glycolysis into pyruvate, by pentose phosphate pathway into ribose-5-P
(3) Structural polymers: can be used to make ECM and cell wall polysaccharides
Glucose source
- 1 hr after meal
- 4 h after meal
- 2 days after meal
- Dietary glucose
- Glycogenolysis (glycogen runs out 12-14h after meal)
- Gluconeogensis
Important enzymes for regulation of blood glucose after meal
In glycolysis:
Glucokinase (Glucose –> Glucose-6-P)
PFK1 (Fructose-6-P to Fructose-1,6-BP)
Pyruvate kinase (PEP –> Pyruvate)
Glycolysis nets:
2ATP, 2NADH, 2 Pyruvate
How does glucose get into cells?
Sodium independent transporters: GLUT1-GLUT14
Sodium cotransporter system (SGLT)
Hexokinase is found? Km/Vmax?
Glucokinase is found? Km/Vmax? Regulated by?
Hexokinase found in most cells. Low Km/Vmax
Glucokinase found in pancreatic beta cells. High Km/Vmax (allows pancreas to sense high levels of glucose). Regulated by glucokinase regulatory protein found in liver.
MODY Type 2
Maturity onset diabetes of young. Mutations of glucokinase causes it.
All carboxylases uses ___ as cofactor
Biotin
Fates of pyruvate
(1) Turned into OAA by pyruvate carboxylase
(2) Turned into lactate by lactate dehydrogenase (anaerobic)
(3) Turned into AcetylCoA by pyruvate dehydrogenase complex
Cori Cycle
Cycling of glucose and lactate between muscle and liver. In working muscle, Glucose –> pyruvate –> lactate; Lactate taken to liver and converted back to pyruvate before being transported back to muscle.
Pyruvate dehydrogenase
- Does
- Uses what as cofactor?
- Active in what form?
- Turns pyruvate into Acetyl CoA, release CO2.
- Uses thiamine as cofactor. Thiamine deficiency increases lactate bc pyruvate DH can’t make acetyl CoA
- Active when deppylated by PDH phosphatase (PDH kinase ppylates). PDH phophatase up-regulated by insulin and ADH.
- Pyruvate and Ca2+ upregulate. ATP, acetyl CoA, NADH inhibit.
Glucose-6-phosphatase
- Is expressed where?
- Does what?
- Defect leads to what?
- Only expressed in liver and kidney ER.
- Turns Glucose-6-P back into free glucose.
- Von Gierke Disease –> can’t convert/generate free glucose. Large liver, short stature, low blood sugar. Increase gluconeogenesis, elevated lactate/acetyl CoA and alanine
What transports glucose out of cell
GLUT2
What regulates glucokinase?
Glucose +
Insulin +
Glucagon -
Fructose-6-P -
What regulates PFK-1?
Fructose-2,6-BP + Insulin + Glucagon - ATP - Citrate -
What regulates pyruvate kinase?
F-1,6,-BP +
ATP - (by Mg2+ sequestration)
Glucagon - (by protein kinase A activation)
Alanine -
Glycolysis mainly occurs in?
Muscles and brain
Pentose phosphate shunt
Anaerobic non-ATP-production path that produces NADPH (useful for anabolism and resisting oxidative stress) and ribulose-5-phosphate (useful precursor for anabolic pathways).
Uses Glucose-6-P dehydrogenase (G6PD). NADPH downregulates G6PD, directing G6P to glycolysis if NADPH is too high.
TCA Cycle produces?
3 NADH, 1 FADH2, 1 GTP (or ATP)
Each glucose runs TCA twice.
ATP yield of breakdown of one glucose
Glycolysis: 2 ATP, 2 NADH = 5 or 7 ATP
Pyruvate oxidation: 1 NADH x 2 = 2 NADH = 5 ATP
TCA: (3 NADH, 1 FADH2, 1 GTP/ATP) x 2 = 6 NADH, 2 FADH2, 2 ATP = 15ATP + 3 ATP + 2 ATP = 20 ATP
Total = 30-32 ATP
VDAC
Voltage dependent anionic channel (porin). Imports large anionic molecules into intermembrane space of mitochondria (but need a transporter to get into matrix)
Mitochondria is divided into
(1) Outermembrane: protein transport
(2) Intermembrane space: electron transport chain; lower pH and more oxidizing than cytosol
(3) Inner membrane: oxidative ppylation
(4) Matrix: Krebs cycle
Mitochondrial genome
Own circular genome, but only has 37 genes. Most mt genes are in the nuclear genome
Cardiolipins
Embedded in inner mt membrane and stabilizes Complex IV of ETC
