Overview of Carbohydrate Metabolism and its Regulation Flashcards
What happens during the fed state?
Think insulin! Glu inside cell, gets phosprolyated. Glu goes to pyruvate. Pyruvate sometimes is parked as lactate.
Pyv to Acetyl-CoA in mitochondria through Krebs Cycle. We dont get much atp out of Krebs but many electrons from NAD and FAD. Inside of mitochondria electrons are stuck on O2 to make water. In liver and muscle excess glu is stored as glycogen. All tissues use Hexose phosphate shunt to make as much NADPH as they need. In fed state when there is lots of acoa and ATP, excess ACoA is made into fa and this happens in adipose tissue and liver.
What is happening in the fasting state?
Think glucagon! No glu is coming in. Liover breaks down gly to glu-6-P goes into bld to maintain blodd glucose levels. OAA comes out of the Krebs Cycle to make glu-6-p to supplement depleting gly stores. Triglycerides to FA are beta oxidized to ACoA to give you energy in Krebs Cycle. Urea cycle takes waste amino groups for secretion.
Describe glycolysis
Fundamental energy-producing pathway common to all cells
- Occurs in cytosol
- Partial [ox] of glucose
- Immediate energy source - but limited amounts
- Source of reducing equivalents (NADH:)
- Lowers pH of cell
2 fates:
- Krebs Cycle (aerobic- O2 and mitochondria present)
- lactate (anaerobic-no O2 and no mitochondria)
Describe the Krebs Cycle
occurs only in mitochondria - powerhouses of cells
converts 3C pyruvate to CO2 & H2O
forms 1 GTP = ATP
forms energy-rich reducing equivalents
Pyr dH makes 1 NADH:
Krebs Cycle makes 3 NADH: + 1 FADH2:
(used to make lots of ATP)
Central pathway of metabolism
- CH2O arrow energy, fat, protein
- protein arrow energy, CH2O, fat
- fat arrow energy
THE Major source of energy (ATP) for most cells
Describe oxidative phosphorylation and ETC
Occurs inside mitochondria & requires O2 (aerobic)
ATP production from energetic electrons on NADH: & FADH2:
Because NADH: & FADH2: come from Krebs Cycle, it also requires O2
Key Corollaries
- CH2O can generate energy (ATP) in absence of mitochondria &/or O2 because glycolysis generates (a little) ATP in cytosol
- Protein & fat require mitochondria and O2 for energy production
Describe PPP (HMS)
- Occurs in cytosol of all cells
- Branches off from glycolysis
- Produces nadph: for biosynthetic rx
- fatty acid synthesis
- cholesterol synthesis
- reduced glutathione (GSH) (protects RBC membranes
produces ribose-P for nucleotide biosynthesis
Unneeded Ribose-P re-enters glycolysis to make ATP & pyruvate. That’s why we call it a shunt!
Describe gluconeogensis
Liver makes new glucose to maintain blood glucose levels during fasting & exercise. Kidney helps eventually.
Adequate blood [glucose] critical for brain & RBC (limited liver glycogen)
Both lactate and amino acids can beconverted to glucose
Pyruvate arrow OAA takes place in mitochondria
Anabolic process – requires 6 ~P and NADH:
What is glycogenesis and what is glycogenolysis?
Glycogenesis: Synthesis of glycogen
Glycogenolysis: Breakdown of glycogen
What is glycogen?
Glycogen is a storage form of glucose (large branched-chain glucose polymer)
Where does glycogen metabolism take place?
Primarily in the liver, muscle and kidney
What happens to glycogen in the fed and fasting state in the liver and kidney?
Fed state: Glycogen is formed
Fasting state AND during exercise: Glycogen is broken down to maintain blood glucose levels
What happens to glycogen in the fed and fasting state in the muscle?
Fed state: Glycogen is formed
During exercise: Glycogen is utilized by the muscle during exercise (So the glycogen stays inside of the muscle and has no effect on blood [glucose]
Describe erythrocytes
-Bags of hemoglobin with no nucleus
-Carries O2 to peripheral tissues
-No mitochondria
- use (anaerobic) glycolysis to make ATP
- depend on glucose for energy - cannot metabolize fats or protein
- no glycogen stores; need constant supply of
glucose
-Most pyruvate converted to lactate (lactate dehydrogenase rx)
- Lactate transported out of cell - converted back to pyruvate in liver (Cori Cycle)
-PPP arrow NADPH: to maintain high levels of reduced glutathione (good for getting rid of toxic reactive O2 species, Hydrogen peroxide species, free radical, ; little ribose-5-P needed (protects RBC membranes)
PPP very robust in rbcs and thats why they make pyruvate
How does the brain relate to glycogen and glucose?
It is a critical organ with very high energy demands.
It has lots of mitochondria. Needs & gets lots of O2 (2% body mass uses 20% O2)Needs & gets lots of glucose. Makes and uses lots of ATP (aerobic metabolism)
No significant glycogen stores
Cannot use fat - fatty acids do NOT cross the “blood-brain barrier”
Thus, requires constant glucose supply (~120 g/day)
Can slowly adapt to ketone bodies as energy sources during prolonged fasting & starvation
(important survival mechanism)
What do you know about adipose tissue?
- major synthesis site for triglycerides (fat) (liver is the other)
- major storage site for triglycerides (fat)
- insulin-sensitive glucose uptake (fed state) - lots of glucose uptake (GLUT4)
- lots of FA synthesis
insulin-sensitive glucose uptake (fed state)
- lots of glucose uptake (GLUT4)
- lots of FA synthesis
both glycolysis & PPP active
some acetyl~CoA (from glucose) used for energy production
- Citric acid cycle arrow ATP
excess acetyl~CoA converted to fat
PPP arrow NADPH: for fatty acid biosynthesis (ATP needed too!)
minimal glycogen stores for energy; not dependent on glucose for energy (can use its own fat)
FA from TG released into blood during fasting; major energy source
