Lipid metabolism (wk8) Flashcards
How does the human body process dietary fat?
-Triacylglycerol (digestion and absorption)
-Triacylglycerol (digestion and absorption) -> There are 3 fatty acids which combine to 1 glycerol. Majority of lipids from dietary fat of which around 90-95% are triacylglycerols. Serve as an energy store in adipose tissue and muscle. One glycerol unit and 3 fatty acids connected by ester bonds. Triacylglycerol cannot pass the membrane of gastrointestinal cells and must be broken down.
How does the human body process dietary fat?
-Triacylglycerol (digestion and absorption) - hydrophobic molecules are processed through (4 stage process)
- Ingestion: Large coarse lipids droplets are reduced in size to fine liquid droplets by bile acids, made in liver and released by gallbladder.
- Intestinal lumen: pancreatic lipase hydrolyses the ester bonds to yield 2 fatty acids and 2-monoacylglycerol
- Enterocytes: these products freely enter the intestinal cells where TAG is reformed
- Bloodstream: all lipids are packaged into chylomicrons and exported into lymph nodes and then the blood where the lipids can be distributed after each meal (several hours)
How does the human body process dietary fat (digestion, absorption and transport)
-Transport of insoluble triacylglycerol
-Transport of insoluble triacylglycerol -> Chylomicrons are a class of lipoproteins – HDL, LDL, vLDL are others. Single layer of phospholipids with a hydrophobic core. Once formed, Chylomicrons pass into extracellular space, then into lymphatic vessels and then into blood circulation. This process happens for a number of hours after a meal.
-‘Ase’= enzyme which can break down a fat
How fats are used to fuel exercise? (lipolysis, adipose tissue and muscle)
-Fat content of the human body
-Fat content of the human body -> Lipid is mainly stored in specialised tissue called adipose tissues, as well as muscle (0.2-0.8%). Adipose tissue is found both under the skin (subcutaneous fat) ad around our internal organs (visceral fat) ~15% in men and ~23% in women. The cytoplasm of adipocyte is dominated by a large lipid droplet filled with triacylglycerol (~80%). This serves as a huge energy reserve, which can be utilised by working muscles for fuel during exercise. Changes in Triacylglycerol breakdown (lipolysis) and synthesis occur in adipose tissue and muscle during exercise. Important to consume cholesterol in the diet to allow the body and brain to function.
How fats are used to fuel exercise? (lipolysis, adipose tissue and muscle)
-Lipolysis in skeletal muscle (the breakdown of fuel as fuel)
-Lipolysis in skeletal muscle (the breakdown of fuel as fuel) -> Triacylglycerol stores are contained in lipid droplets within adipocytes or muscle fibres (next to mitochondria). The proximity of lipid droplets to mitochondria minimises the distance fatty acids move for degradation and ATP production. 3 key enzymes are all located in type-1 muscle fibres, making lipolysis optimal during aerobic exercise. Exercise speeds up FFA degradation in adipose tissue and muscle by a process called b(beta)-oxidation. The product of b(beta)-oxidation (acetyl CoA) enters the TCA cycle.
Describe lipolysis (the breakdown of triacylglycerol)
-Breakdown and cytosol and fed state
-Lipolysis (the breakdown of triacylglycerol) -> Adipose tissue and muscle contain the necessary enzymes to drive lipolysis and synthesis of triacylglycerol.
* Triacylglycerol breakdown occurs in the cytosol via 3 enzymes:
1. Adipose TAG Lipase (AGTL)
2. Hormone sensitive lipase (HSL)
3. Monoacylglycerol acyltransferase (MGL)
* Triacylglycerol synthesis also occurs in the cytosol:
- Glycerol generated from dietary glucose forms the TAG glycerol backbone
- Three fatty acids are then added in 2 steps via the enzyme glycerol phosphate acyltransferase
-In a fed state: synthesis > breakdown. During exercise: breakdown > synthesis.
How does exercise impact lipolysis
-How does exercise impact lipolysis -> The rate of lipolysis in adipose tissue increases within 5-10 minutes of exercise onset. The rate of lipolysis in adipose tissue is influenced by:
1. Epinephrine: Increases lipolysis (b(beta)-adrenergic pathway)
2. Epinephrine also decreases lipolysis (a(alpha)-adrenergic pathway)
3. Insulin reduces lipolysis
* Low-moderate intensity exercise -> Increased epinephrine and decreased insulin drive the cAMP pathway favourably to activate AGTL, HSL and MGL
* High intensity exercise -> Increased epinephrine and stable or increased insulin supresses the cAMP pathway to inhibit AGTL, HSL and MGL.
What is the energy yield of fatty acid degradation and how does it compare to carbohydrate use
-Include: interconversion of carbs and lipids and conversion of fatty acids to glucose
-Interconversion of carbohydrate and lipids -> Carbohydrates are much more rapid at regenerating ATP, yet, Lipids are a much greater source or energy. There are several points at which carbohydrate and lipid metabolism connect:
* Glycerol – Can be converted to glucose in the liver, however, glycerol forms a minor part of triacylglycerol
* Fatty acids – Meet at AcetylCoA but cannot be converted back to pyruvate
* Oxyloacetate – No net conversation of AcetylCoA, carbons lots at CO2
We are unable to convert fatty acids into glucose. However, we are able to convert glucose into fatty acids through AcetylCoA and through L-glycerol-3-phosphate (intermediate of glycoloyis). Although, this is minimal under physiological conditions.
How is lipid metabolism used under different intensities of exercise
-What are lipids, how lipids differ from carbohydrates and phospholipids
-What are lipids? -> Diverse biological compounds, characterized by low solubility in water.
* Fatty acids and Triacylglycerols are 2 important energy sources with high ATP yield but a slow rate of oxidation.
* Steroid – Cell signalling and membrane function (sterols). Form hormones like cortisol.
* Phospholipids – Form membranes and are present at the interface between lipid and water. Important in creating the structure of the cell. There are aisles which allow movement and communication throughout the body.
-How do lipids differ from carbohydrates? -> Carbohydrates are hydrophilic, whereas lipids are largely hydrophobic (polar heads of phospholipids and cholesterol are hydrophilic). The longer the fatty acid chain and fewer the double bonds, the lower the solubility in water. The differences in structural properties between carbohydrates and lipids alter the manner by which lipids are digested, absorbed and metabolized for energy
-Phospholipids -> Major component of cell membranes that effect cell signalling. Consist of a glycerol unit connected by 2 fatty acids and a phosphoric group (attached to an alcohol) via ester bonds. Membrane lipids are amphipathic meaning one end is hydrophobic, the other hydrophilic.
Describe the fate of lipolytic products during exercise
-The fate of lipolytic products during exercise -> Exercise speeds up lipolysis of Triacylglycerol in both adipose tissue and skeletal muscle.
* Adipocytes – The glycerol and the FFA’s formed by lipolysis in adipocytes leave the tissue and enter the blood carried by Albumin.
* FFA’s from lipolysis in muscle remain and FFA’s from adipose tissue are imported into muscle via fatty acid binding protein at the plasma membrane (FABP-PM)
* Muscle – FFA are primarily used for b(beta)-oxidation and ATP provision
* Liver – glycerol is used for gluconeogenesis and some FFA may enter for Triacylglycerol synthesis
The fate of lipolytic products during exercise
-Fatty acids degradation through the pathway of beta-oxidation in the mitochondria
-The fate of lipolytic products during exercise -> Fatty acids are degraded through the pathway of b(beta)-oxidation in the mitochondria. Beta-oxidation: over a 3-step process, FFA’s (Acyls) are activated (acyl-CoA) and transported across 2 mitochondrial membranes for degradation via a cycle with carnitine:
1. Activation: FFA’s are activated by a reaction with CoA forming Acyl-CoA. This can then pass to the inter membrane space.
2. Carnitine binding: Carnitine takes the Acyl group (Acylcarnitine), allowing transport into the mitochondrial matrix
3. CoA restoration: The acyl chain is then taken from carnitine to reform Acyl-CoA inside the mitochondrial matrix.
Describe Acetyl-coA through the beta-oxidation pathway in the mitochondrial matrix
Acetyl-coA enters the b(beta)-oxidation pathway in the mitochondrial matrix. A single cycle of beta-oxidation (and the TCA cycle) involves 4 reactions that degrade acyl-coa: 1x acetyl coA, 1x FADH2, 1x NADH and Acyl-coA (minus 2 carbons). Acyl-coA then begins another cycle of beta-oxidation. Acyl denotes any fatty acid chain and therefore some fatty acids undergo more cycles of beta-oxidation e.g. palmitate (16 carbons) undergoes 7 cycles.
What is the energy yield of beta-oxidation and the energy yield of fatty acid oxidation
-Energy yield of b(beta)-oxidation -> This is not energetically favoured and produces no ATP, but 8 acetyl coA, 7 FADH2 and 7 NADH that enter TCA cycle and ETC
-Energy yield of fatty acid oxidation -> TCA and ETC ‘pull’ b(beta)-oxidation and yield a huge amount of energy from fatty acid oxidation, e.g. x1 palmitic acid molecule yields 106 ATP molecules.
Describe fatty acids with an odd number of carbons (beta-oxidation)
-Fatty acids with an odd number of carbons (beta-oxidation) -> A small fraction of fatty acids contain an odd number of carbons – this is a problem when beta oxidation removes 2 carbons at a time. Instead once a 5 carbon acylCoA molecule is reaches we get the breakdown into AcetylCoA as normal and a 3-carbon Propionyl CoA molecule. This undergoes a series of 3 reactions, forming Succinyl Coa which enters at reaction 5 of the TCA cycle. This can then be fully oxidised to generate ATP.
Describe how exercise can speed up fatty acid oxidation (4 steps)
-Exercise can speed up fatty acid oxidation -> Exercise can speed up fatty acid oxidation within muscle by:
1. Stimulating lipolysis in adipose tissue and muscle
2. Increasing blood flow to the working muscle, thus increasing FFA delivery
3. Enhancing translocation of fatty acid binding protein at the plasma membrane (FABP-PM) for FFA uptake into muscle
4. Increasing activity of AMP-activated protein kinase (AMPK), which deactivates acetyl coA carboxylase, thus reducing fatty acid synthesis (preventing acetyl CoA from becoming Malonyl CoA)
