Unit 10 - Metabolism & Energy Balance Flashcards
Once nutrients are ingested, digested and absorbed by the digestive system, they can…
be used for various metabolic processes.
Metabolism
Is the sum of all chemical reactions in the body
Metabolism
Includes:
- Anabolic pathways
2. Catabolic pathways
Anabolic pathways
that build larger molecules from smaller ones.
Catabolic pathways
that breakdown larger molecules into smaller ones.
There are two different metabolic states:
- Fed or absorptive state
2. Fasted or post-absorptive state
Fed or absorptive state:
overall ANABOLIC state following a meal when plasma levels of absorbed nutrients are high and are used to build high energy compounds (like ATP and phosphocreatine) or are converted into storage forms for later use.
(period of time following a meal, when the products of digestion are being absorbed, used, & stored)
Fasted or post-absorptive state:
overall CATABOLIC state occurring between meals when plasma levels of absorbed nutrients are low and the body breaks down stored nutrients (i.e. taps into its stored reserves) to obtain the molecules needed
(once nutrients from a recent meal are no longer in the bloodstream & avail. for use by the tissues, the body enters this state)
The fate of absorbed nutrients is one of the following:
- Energy production.
- Synthesis
- Storage.
Energy production.
Biomolecules are broken down, releasing energy that is stored in the bonds of high energy molecules like ATP, phosphocreatine
Synthesis
of biomolecules required for growth and maintenance of tissues (for example, synthesis of cell
membranes and membrane proteins, synthesis of actin and myosin in muscle cells, etc.)
Storage.
When plasma levels of an ingested nutrient exceeds the levels required for energy production and synthesis, the remainder is stored as either glycogen or fat (mostly the latter since glycogen stores in the liver and skeletal muscle tissue are limited).
Whether a nutrient is used for energy production, synthesis of biomolecules or is stored depends on…
whether the body is in the fed or fasted state.
Carbohydrate Metabolism
Fed (Absorptive) State Metabolism:
After absorption, almost all absorbed monosaccharides that are not glucose (i.e. fructose and galactose) are converted to glucose in the liver. As a result, 95% of all monosaccharides circulating in the blood plasma are glucose.
Circulating glucose enters tissue cells (e.g. skeletal muscle cells) by facilitated diffusion using GLUT (glucose transport) carrier proteins.
Once inside of cells, glucose is immediately phosphorylated into GLUCOSE-6-PHOSPHATE via the action of the enzyme GLUCOKINASE (in liver cells) or HEXOKINASE (all other cells). This helps to trap glucose inside of the cell and maintain concentration gradients of glucose that favour movement of glucose into the cells.
Carbohydrate Metabolism
Fed (Absorptive) State Metabolism:
The type of GLUT used is specific to the tissue:
a. GLUT2 in liver (similar to kidney).
b. GLUT3 in neurons.
c. GLUT4 in skeletal and cardiac muscle cells, and adipose cells. Insulin increases the number of GLUT4 proteins in cell membranes and therefore increases glucose transport into these cells.
Carbohydrate Metabolism
Fed (Absorptive) State Metabolism:
During the fed state, glucose-6-phosphate is:
a. Converted into ATP via glycolysis, the citric acid cycle, and the electron transport chain (aerobic pathways for ATP synthesis)
b. Stored as glycogen.
c. Stored as fat.
d. Used for lipoprotein synthesis.
Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:
During the fed state, glucose-6-phosphate is:
a. Converted into ATP via glycolysis, the citric acid cycle, and the electron transport chain (aerobic pathways for ATP synthesis)
i. GLYCOLYSIS = conversion of glucose-6-phostphate to 2 pyruvate, in the cytosol of the cell. Produces net 2 ATP.
ii. In mitochondria, pyruvate is converted to Acetyl Coenzyme A.
iii. Acetyl CoA enters the CITRIC ACID CYCLE (aka Krebs cycle), and under the effects of multiple enzymes is converted into a cascade of products, the end results of which produces net 2 ATP, along with carbon dioxide and hydrogen ions and high energy electrons.
iv. The flow of H+ down a gradient is involved in the oxidative phosphorylation of ADP to ATP in the ELECTRON TRANSPORT CHAIN (ETC) process. The ETC produces net 28 ATP.
v. Overall net ~32 ATP are produced by this process.
Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:
During the fed state, glucose-6-phosphate is:
b. Stored as glycogen.
- Glycogenesis = formation of glycogen (a polymer
of glucose) from glucose. - Glycogen stores are limited – they store enough glycogen to satisfy the body’s energy needs for 12-24 hours.
- Steps:
i. Glucose-6-phosphate is converted to
glucose-1-phosphate.
ii. glucose 1-phosphate is converted to uridine- diphosphate glucose
iii. Uridine diphosphate glucose is converted to glycogen.
Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:
During the fed state, glucose-6-phosphate is:
c. Stored as fat.
Any excess glucose is converted to triglycerides and stored in adipose tissue (LIPOGENESIS). Involves:
i. Conversion of glucose and/or glycolysis intermediates into glycerol.
ii. Conversion of acetyl CoA molecules (produced as a result of glucose catabolism) into fatty acids via the action of FATTY ACID SYNTHETASE.
iii. Inside of the smooth ER, the glycerol from (a) and the fatty acids from (b) are combined to form triglycerides.
Carbohydrate Metabolism
1. Fed (Absorptive) State Metabolism:
During the fed state, glucose-6-phosphate is:
d. Used for lipoprotein synthesis.
Acetyl CoA from glucose metabolism can be used for production of lipoproteins (e.g. LDL and HDL). Lipoproteins are responsible for carrying insoluble fat and cholesterol in the plasma.
LDL =
low density lipoproteins
HDL =
high density lipoproteins
Carbohydrate Metabolism
- Fasted (Post-Absorptive) State Metabolism:
During the fasted state, stored carbohydrates are converted back into glucose to be used for ATP production (meets energy demands between meals).
a. Glycogenolysis: Glycogen is converted to glucose-6- phosphate and glucose. Involves:
i. Conversion of glycogen into Glucose-1-phosphate, through the action of the enzyme phosphorylase.
ii. Conversion of Glucose-1-phosphate to glucose-6- phosphate.
iii. Glucose-6-phosphate can then enter glycolysis in the cell or be converted to glucose (via the enzyme
glucose phosphatase) and released into the blood).
b. Gluconeogenesis: production of glucose from substrates other than glycogen, including amino acids and triglycerides.
Glycogenolysis:
Glycogen is converted to glucose-6- phosphate and glucose.
Gluconeogenesis:
production of glucose from substrates other than glycogen, including amino acids and triglycerides.
Glycogen can be converted directly to glucose 6-phosphate by the addition of phosphate. Glycogen that is broken down first to glucose & then phosphorylated…
“costs” the cell an extra ATP
Lipid Metabolism
1. Fed (Absorptive) State Metabolism:
Recall from Unit 9 – most lipids are packaged into lipoproteins/lipid complexes called CHYLOMICRONS, which exit enterocytes via exocytosis and are absorbed by the lymph lacteals. Some short chain fatty acids (less than 12 carbons long) are absorbed into the blood by simple diffusion.
Chylomicrons contain
triglycerides (87%), phospholipids (9%), cholesterol (3%) and apolipoprotein (1%).
Lipid Metabolism
1. Fed (Absorptive) State Metabolism:
During the fed state:
a. The enzyme LIPOPROTEIN LIPASE (found on the capillary endothelium in adipose, liver and muscle tissues) breaks down the triglycerides of the chylomicron into monoglycerides and fatty acids that can diffuse into tissue cells.
b. Adipose and liver cells convert monoglycerides and fatty acids into triglycerides (LIPOGENESIS), and store them until needed. High insulin levels during the fed state suppress fatty acid oxidation in other tissues (e.g. skeletal muscle) and increase oxidation of glucose.
c. The leftover parts of the chylomicron (namely the apolipoprotein and cholesterol) are taken to the liver.
d. LDL-C is transported to cells that will use the cholesterol for synthesis (e.g. building cell membranes, steroid hormone synthesis, etc).
e. Excess glucose and protein are converted to triglycerides
- LIPOGENESIS – glucose or amino acids are converted to pyruvate and then to Acetyl CoA. Acetyl CoA is used to produce fatty acids, which can then be incorporated into triglycerides in adipose tissue cells (or liver cells) for storage.
Cholesterol can be used…
to form bile acids/salts, or can be repackaged into lipoproteins formed in the liver.
(the body can make cholesterol from acetyl CoA through a series of rxns)
Cholesterol can be used to form bile acids/salts, or can be repackaged into lipoproteins formed in the liver. The most important are the
LOW DENSITY LIPOPROTEINS (including LDL cholesterol, LDL-C) and HIGH DENSITY LIPOPROTEINS (like HDL cholesterol, HDL-C).
Lipoproteins that have a high concentration of protein are
high density
LDL cholesterol (LDL-C)
is known to cause atherosclerosis (build up of lipid plaques inside blood vessels), leading to arteriosclerosis (stiffening of blood vessels) that can cause high blood pressure, cardiovascular disease, stroke, etc.
(“lethal cholesterol”)
HDL-C
is “healthy” cholesterol as it carries cholesterol back to the liver where it can be eliminated in bile.
Lipid Metabolism
- Fasted (Post-Absorptive) State Metabolism:
Most of the body’s energy reserves are stored as lipids. During the fasted state (in between meals), stored triglycerides are broken down and the components used in various pathways to meet energy demands between meals.
Involves:
a. Lipolysis
Lipid Metabolism
- Fasted (Post-Absorptive) State Metabolism:
Involves:
a. Lipolysis – breakdown of triglycerides into fatty acids and glycerol for ATP production.
i. Triglycerides in adipose tissue are hydrolyzed into glycerol and fatty acids by the intracellular enzyme HORMONE SENSITIVE-LIPASE (HSL).
ii. Glycerol is transported to the liver where it undergoes GLUCONEOGENESIS to become glucose, which can then be used as a substrate for glycolysis and ATP production in various tissues (skeletal muscle, brain, etc).
iii. Fatty acids are transported in the blood bound to albumins:
• At target tissues they enter the mitochondria and undergo BETA-OXIDATION which removes 2-carbon acyl units from the fatty acid. These acyl units are then converted into acetyl CoA which is used in the citric acid cycle to produce ATP.
• In the liver, fatty acids undergo beta-oxidation to form ketone bodies. Ketones can then be used as an energy source to produce ATP (particularly by the brain during starvation).
Protein Metabolism
- Fed (Absorptive) State Metabolism:
- Recall from Unit 9 – most proteins are absorbed as amino acids.
- After absorption into the blood, they are first delivered to the liver, which uses them to synthesize plasma proteins like albumins and lipoprotein (such as LDL-C and HDL-C) that will transport lipids in the blood. Amino acids are then circulated to the rest of the tissues in the body and used by cells for protein synthesis (via transcription and translation of DNA and mRNA).
Protein Metabolism
- Fed (Absorptive) State Metabolism:
- Recall from Unit 9 – most proteins are absorbed as amino acids.
- After absorption into the blood, they are first delivered to the liver, which uses them to synthesize plasma proteins like albumins and lipoprotein (such as LDL-C and HDL-C) that will transport lipids in the blood. Amino acids are then circulated to the rest of the tissues in the body and used by cells for protein synthesis (via transcription and translation of DNA and mRNA).
Protein Metabolism
- Fed (Absorptive) State Metabolism:
Unlike for carbohydrates and lipids, there is no…
storage form of amino acids in the body. Excess amino acids in the blood can be converted to pyruvate (through the process of deamination – removal of an amino group – NH2). Pyruvate is then converted to Acetyl CoA in the mitochondria, and can be used for:
- Lipogenesis – by converting Acetyl CoA into fatty acids.
- Aerobic production of ATP (enters citric acid cycle).
If glucose intake is LOW…
AA’s can be used for energy (in fasted-state)
If more protein is ingested than is needed for syn. & energy expenditures…
excess AA’s are converted to fat
When AA intake exceeds the body’s need for protein syn…
excess AA’s are burned for energy or stored as fat
Protein Metabolism
- Fasted (Post-Absorptive) State Metabolism:
- Free amino acids in the blood are be used to make ATP. If the fasted state lasts a particularly long time (e.g. starvation), then the body will actively breakdown muscle tissue to supply amino acids for protein synthesis and for ATP production.
- Like the fed state, amino acids undergo deamination – removal of an amino group (NH2), which forms ammonia (NH3) and and an organic acid.
- Organic acid can enter the citric acid cycle to produce ATP.
- NH3 is toxic, and so is converted to ammonium (also toxic) and then into urea in the liver. Urea can then be filtered by the kidneys and excreted in the urine (it also contributes to vertical osmotic gradient in the kidney – see unit 8).
Amino acids can also be used to produce glucose via
gluconeogenesis (the reverse of glycolysis).
a. Amino acids are deaminated and their organic acids can either directly undergo gluconeogenesis or they can be converted to pyruvate which will undergo gluconeogenesis.
b. Product of gluconeogenesis is glucose-6-phosphate.
c. Glucose -6-phosphate is converted to glucose (by phosphatase in the liver).
Extrinsic Control of Metabolism
As we have seen in the previous sections, metabolic processes in both the fed and fasted states are mediated by enzymes. Often the forward and reverse reactions are mediated by separate enzymes, which allows for “push-pull” control of a metabolic process by upregulating the activity of one enzyme and downregulating the activity of the other.
Modulation of metabolic enzyme activity occurs as a result of hormonal stimuli, however neural stimuli can also be involved.
Extrinsic Control of Metabolism
Modulation of metabolic enzyme activity occurs as a result of hormonal stimuli, however neural stimuli can also be involved.
- For example: in carbohydrate metabolism, insulin promotes the activity of enzymes that cause glycogen formation (glycogenesis) during the fed state and inhibits enzymes that promote glycogen break down (glycogenolysis).
- In contrast, glucagon promotes the activity of the enzymes that cause glycogenolysis during the fasted state, and inhibits the activity of the enzymes that cause glycogenesis.
Extrinsic Control of Metabolism
An important step in making the transition between fed state and fasted state metabolism is…
the behavioural regulation of food intake and satiety.
Food intake is thought to be controlled by ____ ____ and ____ ____ in the hypothalamus.
feeding centre
satiety centres
Food intake is thought to be controlled by feeding centres and satiety centres in the hypothalamus. Two theories exist as to how these centres are controlled:
- Glucostatic theory
2. Lipostatic theory
Glucostatic theory
suggests that food intake is controlled by blood glucose levels. When blood glucose levels are low the satiety centre is suppressed and the activity of the tonically active feeding centre dominates, causing food intake.
Lipostatic theory
suggests that food intake is controlled by signals from the body’s adipose tissues (fat stores), and that when fat stores are increased, the activity of the feeding centres is inhibited and food intake decreases.
Extrinsic Control of Metabolism
Some peptide hormones and neurotransmitters released by the gut and hypothalamus are known to stimulate the feeding centres of the brain and increase food intake. These include:
- neuropeptide Y (NPY)
2. ghrelin
