Lecture 1: Characteristics of Biomolecules in Health and Disease Flashcards
Major biomolecules that play important roles in cellular functions
Water Carbohydrates (glucose) Proteins (amino acids) Lipids (fatty acids, triglycerides) Sodium Potassium Calcium Bicarbonate Chloride Lactate Pyruvate Acetyl CoA (acetyl coenzyme A
Other major biomolecules
Calcium Bicarbonate Chloride Lactate Pyruvate Acetyl CoA Oxaloacetate
Functions of biomolecules
- Responsible for producing energy through catabolic reactions
- Involved in using up energy for the synthesis of macromolecules through anabolic pathways.
- Useful as micronutrients in the maintenance of health and management of
patients. - Important in cellular functions that maintain life.
- Important as structural components.
Biomolecules are vital constituents of the human body and are responsible for
- Supplying ATP/energy through catabolism of dietary nutrients.
- The synthesis of macromolecules through anabolic pathways (e.g. gluconeogenesis) in cells, using the energy derived from the catabolism of nutrients
- The metabolism of vitamins and micronutrients.
- Maintaining optimal and specific cellular environments
- Controlling specific homeostatic mechanisms in cells
Functions of carbohydrates
Immediate source of energy
Structural molecules
Interact with proteins (glycoproteins) and lipids (glycolipids)
What happens to excess glucose in hyperglycemic patients?
i.e.. diabetes
Excess glucose binds to proteins
Leads to microvascular diseases (atherosclerosis (narrowing and hardening of arteries), nephropathy (kidney disease) and neuropathy (loss of sensation))
= multi-organ failure
What happens when excess glucose binds to hemoglobin in hyperglycemic patients?
Affects Hb’s ability to carry oxygen.
Indicated by A1C value, which is a measure of hyperglycaemia
Three main effects of hyperglycemia
Osmotic effect
Protein glycosylation
Radical effect
What does osmotic effect cause?
Dehydration of cells
Result of movement of water from cells (low concentration, low osmotic pressure) into blood plasma (high concentration, high osmotic pressure)
What happens when there is dehydration of brain cells?
Coma
What is osmotic pressure?
The pressure that needs to be applied to a solvent to prevent is from moving to another compartment by osmosis
What does osmotic effect cause in diabetic patients with hyperglycaemia?
Polyuria (frequent urination)
Thirst
Glycosuria (excess glucose in urine, which leads to excess water excretion in urine as well)
What is the radical effect?
Outcome of hyperglycaemia
Excess glucose can produce reactive oxygen species, which damage cell membrane, DNA and other molecules
What can happen to excess glucose?
Can be converted to glycogen (glycogenesis) in liver and muscles
This serves as a reserve for when there is not enough glucose
What is glycogenolysis?
When the liver breaks down glycogen into glucose to supply extra hepatic tissues with glucose
Liver doesn’t use much glucose itself so that there is some for other organs
When is muscle glucose broken down?
During exertion, when energy production is needed
What lipids can glucose be converted into?
Triglycerides in liver
Fatty acids
Can fatty acids be converted to glucose?
NO (thermodynamic issue)
How does body maintain glucose levels (homeostasis)?
Synthesizes it from other molecules during gluconeogenesis
Where do erythrocytes get energy? And what happens if they do not have energy?
Depend entirely on glucose
Deficiency of energy = destruction/lysis/breakdown?
Where do brain cells get energy under normal conditions?
Entirely from glucose
Where do brain cells get energy during fasting and starvation?
Ketone bodies derived from oxidation of fatty acids
Lack of glucose = unconsciousness and eventually coma
What molecules can glucose be synthesized from during gluconeogenesis?
Glycerol
lactate
Amino acids
Where does gluconeogenesis occur?
Liver and Kidneys only
How are lactate and oxaloacetate produced from glucose?
Glucose -> pyruvate
pyruvate -> lactate and oxaloacetate
How is acetyl CoA produced from glucose?
Glucose -> pyruvate
pyruvate -> acetyl CoA
How is glucose produced from pyruvate?
Pyruvate -> oxaloacetate
Oxaloacetate -> glucose
What can disorders in glucose metabolism (breakdown) lead to?
Hypertriglyeridemia (accumulation of triglycerides)
Hepatomegaly (enlarged liver) due to accumulation of glycogen
Lactic acidosis (due to inhibition of oxidative phosphorylation)
What are triglycerides?
Glycerol + fatty acids
Where are triglycerides found?
Adipose tissues or chylomicrons
Functions of triglycerides
Most useful form of storage energy
Energy source in absence of glucose
Membrane structures in lipid bilayer
Interact with proteins and carbohydrates
What can the metabolization of fatty acids be used for?
To produce energy and ketones
When and why do certain organs use ketones for energy?
Muscles, brain, liver, kidney
Used during fasting
Fatty acids can be converted to…
Acetyl CoA (the reverse is true as well)
Triglycerides (interactions with glycerol)
What happens when there is a disorder in catabolism of fatty acids?
lack of energy
hypertriglyceridemia
fatty degeneration of the liver
during fasting can be fatal because of the lack of glucose.
Why is fatty acid oxidation important for glucose synthesis?
Oxidation of FAs produces ATP that is used in anabolic pathways for glucose synthesis (gluconeogenesis in liver) from glycerol, amino acids and lactate
If there is no FA oxidation during fasting, glucose cannot be produced and organs will fail
Functions of proteins
enzymes
hormones
other signaling molecules
Are proteins a storage form of energy?
NO
But, they can be broken down to amino acids, which can be converted to acetyl coA and metabolized to produce ATP
Proteins can be broken down to amino acids, which can be converted to glucose in the liver.
What happens to the blood when Red blood cells lyse?
High lactate in the blood
What are essential amino acids?
provided externally to the body
What are non essential amino acids?
produced in the body from essential amino acids.
Glucogenic amino acids
can be converted to glucose only via pyruvate
Other amino acids can be either glucogenic or ketogenic, depending on the physiological conditions.
Ketogenic amino acids
can be converted to ketones only via acetyl coA
Other amino acids can be either glucogenic or ketogenic, depending on the physiological conditions.
Breakdown of proteins
Proteins -> amino acids -> ammonia
Ammonia is neurotoxic, and is converted to urea in the liver
What excretes urea?
Kidneys
What happens when someone has a disorder in protein/amino acids metabolism?
Can lead to high levels of ammonia (hyperammonaemia), which can adversely affect the central nervous system and causes developmental delays.
What is calcium important for?
muscle contraction
What is calcium phosphate important for?
bone formation
What are sodium and potassium important for?
maintaining the sodium-potassium gradient to propagate action potentials/nerve impulses
What are bicarbonate ions important for?
act as buffer system to reduce acidity
What are Chloride ions important for?
allow for osmotic effect and hence flow of water.
What are trace elements important for?
functions of cellular proteins and processes.
vitamins and minerals are important as cofactors and coenzymes for enzymatic activities
What is the central molecule that connects the metabolic pathways of proteins, carbohydrates and lipids?
Acetyl CoA
Also, all dietary nutrients and proteins can be converted to acetyl coA
(see figure)
What does acetyl-CoA interact with in TCA?
Oxaloacetate
Forms carbon dioxide, water, energy and reduced coenzymes (NADH)
How is pyruvate linked to the TCA/Krebs cycle
Via acetyl CoA
How can triglycerides be converted to glucose?
Triglyceride is broken down into glycerol and fatty acids, then glycerol is converted to glucose in the liver
How does hyperglycemia leads to diabetic foot ulcer?
interaction of glucose with proteins leading to glycosylated proteins.
glycosylated proteins produce deleterious effects in different tissues leading to peripheral neuropathy, nephropathy, and optic neuropathy, and cardiovascular diseases.
What does fatty degeneration of muscles lead to?
Muscle damage
Myalgia (muscle pain)
Myoglobinuria (myoglobin in urine)
Respiratory distress (release of ion from Mb that can radicalize and oxidize proteins)
Kidney stones (precipitates formed by Mb)
What does abnormal lipid metabolism cause?
Fatty liver disease
Enlarged due to fat deposits
What does pyruvate link to gluconeogenesis?
Lactic acid
Oxaloacetate