Energy Metabolism Flashcards
What is the difference between oxidation and reduction reactions?
Oxidation = The loss of electrons. Occurs if a compound gains O or loses H Reduction = the gain of electrons. Occurs if a compound loses O or gains H
Describe the roles of niacin and riboflavin in energy metabolism
They function in their coenzyme forms to shuttle H+ ions from energy-yielding compounds to O. This helps produce ATP
Describe the 4 steps in ATP production from carbohydrates
Glycolysis:
Glucose oxidised to 2 pyruvate in 8 steps, producing NADH, H+ and ATP
In RBCs this is the only pathway for energy production
At Fructose 1,6-biphosphate the molecule splits, allowing the glycolytic process to form 2 pyruvate
Glycogen –> glucose costs 1 ATP
Transition reaction:
Pyruvate is metabolised to acetyl coenzyme A (CoA) by pyruvate dehydrogenase, producing NADH, H+ and CO2
One-way pathway
Citric acid cycle:
Acetyl CoA enters the CAC and produces NADH, H+, FADH2, ATP and CO2 in 8 steps
This is not a “closed” cycle
First step: Acetyl CoA combines with Oxaloacetate (4-carbon) to form Citrate (6-carbon)
Electron transport chain (oxidative phosphorylation):
NADH, H+ and FADH2 supply electrons and H ions to the electron transport chain (ETC) and are oxidised to NAD+ and FAD
Electrons are passed along a series of electron carrier membrane proteins, releasing energy to pump H ions into the inter-membranous space of the mitochondria
H+ ions travel down their concentration gradient from the inter-membrane space back into the mitochondrial matrix though ATP synthase, powering the formation of ATP from ADP + Pi
Once inside the mitochondrial matrix, these H+ ions combine with electrons from the ETC and O to form water
What occurs in cells when oxygen is not available?
Anaerobic metabolism occurs in cells with no mitochondria (e.g. RBC) or in any cells when there is no O available
Pyruvate is converted to lactate: Pyruvate + HADH + H+ –>. Lactate + NAD+
NAD+ is then regenerated to fuel glycolysis
The liver cant convert lactate to pyruvate or glucose (CORI cycle) and other intermediates of aerobic respiration
What are ketone bodies (KB)?
There are 3 ketone bodies (KB): acetone, aceto-acetate and beta-hydroxybutyrate
How/where are KB formed and used?
KB are formed in the liver primarily from the breakdown of FA. A small amount are produced from the carbon skeleton of ketogenic amino acids, in the adequate metabolic conditions (low insulin)
What is the difference between ketogenesis, ketosis, ketonemia and ketoacidosis?
Ketogenesis = production of ketone bodies Ketosis = state of ketone bodies rising in blood Ketonemia = more significant rise than above Ketoacidosis = when the blood pH is lowered due to concentration of ketone bodies (bad)
Can typical FAs be used as substrate for gluconeogenesis?
No. The CAC is not a closed cycle and conversion of pyruvate to acetyl CoA is irreversible
What is the starting molecule in lipogenesis?
Acetyl CoA
What happens if there is an excess of acetyl CoA?
Ketogenesis
Caused by beta-oxidation of FA and low energy demands. This occurs in the fasted state in the presence of glucagon. As such, acetyl CoA will likely not undergo lipogenesis.
Ketogenesis occurs when the oxidation rate of fat exceeds ATP demand –> excess acetyl CoA diverted to ketone body formation. This occurs when fat is the primary source of energy
- Untreated type 1 diabetes (cellular glucose uptake is limited)
- Low CHO/high fat diets (!50-100g CHO/day, or 8-10% of EER)
- Fasting or severe restriction --> endogenous fat stores are used for energy
What is the first step involved in ATP production from protein
Deamination
Describe the 5 key factors which regulate energy metabolism
The liver:
First organ to receive most nutrients from the GIT via portal vein
Major site of nutrient conversion and metabolism; also site of ketone body production
Storage of glycogen (~100g) and some triglycerides: <5% of SA in the healthy status, more in obesity and related disease (fatty liver, type 2 diabetes etc.)
When there is poor liver health, energy metabolism is impaired
Substrate availability:
Abundance of dietary substrates = anabolism
Scarcity of dietary substrate = catabolism
The type of substrate, and how much is available determines the kind of metabolism that takes place. Hormones, minerals, vitamins etc.
ATP availability and AMPK (AMP-activated protein kinase):
~100g of ATP is available in the body at any one time, and is constantly being recycled between ATP, ADP and AMP
AMPK responds to high ratio of AMP to ATP in the cell. When activated, it promotes nutrient catabolism to increase ATP production
Functioning enzymes and availability of vitamins and minerals as co-factors:
Required for the pathways to occur adequately, and are rate limiting
Hormones in dominant activity:
Hormones activate transcription factors that up-regulate the expression of genes, coding for enzymes in anabolism or catabolism pathways –> drives the activity of the pathways. Insulin and glucagon
What are the stages in fasting energy metabolism?
- Hepatic glycogen breakdown: to maintain blood glucose level (BGL) and generation of ATP until stores last
- Muscle glycogen provides energy source to muscle until stores last, but does contribute to BGL
- Muscle protein breakdown: AA (carbon skeletons) are used as substrate for gluconeogenesis once glycogen runs out. Also used for ATP production
- Fat breakdown- becomes the main source of energy during extended fasting, glycerol used for glucogenesis, FA undergo beta-oxidation for ATP production
- Ketogenesis and the “metabolic switch”: ketone bodies are produced and brain, heart, muscles, kidneys switch to this alternate fuel. KB are produced as body fat stores become the main source of substrate in prolonged fasting, in order to preserve muscle mass
How is an individuals energy requirements determined?
ER = BMR x PAL
BMR is the amount of energy (ATP) required to keep the body alive (active transport, active metabolic processes to product ATP, and to maintain organ function etc.)
- Measured by direct or indirect calorimetry (measuring O2 and CO2 gas exchange as a measure of how much substrate is oxidised to derive a total amount of kJ/min/kg of body weight), or by the "doubly labelled water" method (gold standard - Estimated by equations derived from population studies (e.g. Harris-Benedict equation or Schofield equation) using the doubly labelled water, standardising per weight, physical activity level, age, sex. When BMR is estimated, the calculation for ER is EER (estimated energy requirement)
PAL is a factor to account for the level of physical activity (PA), be it structured, or any PA performed upon rising
Can use EER to calculate macronutrient distribution ranges
