Tutorial 1 Alterations in digestion, metabolism and energy production Flashcards
Carbohydrates, Fats, and Proteins metabolic process:
These three nutrients are digested in the small intestine, in which:
- Carbohydrates are metabolised into glucose by amylase;
- Proteins are catabolized into amino acids by proteases;
- Fats are digested into fatty acids and glycerol by lipase;
Glucose will be broken down into pyruvate through the cytoplasmic pathway, namely glycolysis, while releasing energy.
The catabolism products of pyruvate, amino acids, and long-chain fatty acids enter the mitochondria, and degraded into Acetyl-CoA by oxidation, which later participates in ‘The Citric Acid Cycle’ (TCA) in energy generation (electron transport chain in producing ATP).
Write the chemical equation for energy production:
Glucose + Oxygen —(energy release)— carbon dioxide + water
Name the source of energy that fuels cellular functions:
ATP (Adenosine Triphosphate):
- The Citric Acid Cycle (TCA) generates energy through oxidisation of acetate derived from the byproducts of digestion (carbohydrates, fats, and proteins) into CO2;
- The cycle also provides precursors e.g. certain amino acids and the reducing agent NADH (Nicotinamide adenine dinucleotide), an important coenzyme facilitating anti-fatigue and bodily endurance.
Which vitamins are essential for mitochondrial function and aerobic respiration?
- Energy production requires the Vitamins B1, B2 & B3
- Vit B1, thiamine, enables the body to use carbohydrates as energy;
- Vit B2, riboflavin, forms FAD (flavin adenine dinucleotide) a redox cofactor - accepts and donates electrons;
- Vit B3, Niacin, forms part of NADH which is involved in redox reactions
Would the availability of oxygen impact on the amount of energy that is produced by the cell?
- During the aerobic respiration, the cell produces 36 ATP, whereas with anaerobic respiration generating 2 ATP
Explain why hypoxia may lead to multiple system failure:
- Although, molecular O2 does not participate directly in TCA cycle, it is essential as the cycle only operates under aerobic conditions as NAD+ and FAD (critical metabolic coenzyme) cannot be regenerated in the absence of O2;
- Oxygen is needed for the Electron Transport Chain in generating ATP
- No O2 means no regeneration of NAD+ and FAD (coenzyme, formed with Vit B2&B3), which ultimately leads to no ATP output, which leads to cellular failure and organ failure
What is glycogen synthesis and where does it take place?
- Glycogen synthesis is the process by which excess glucose is converted into glycogen for storage;
- Liver is the primary storage site of glycogen, although other organs such as the skeletal muscle, heart, kidney and brain can also synthesize glycogen while break it down
Describe the process of Gluconeogenesis:
- Gluconeogenesis is the process by which glucose is made from the biosynthesis of simpler non-carbohydrate precursors e.g. pyruvate
- Examples of non-carbohydrate substances include:
a. lactic acid
b. amino acids
c. glycerol
Jennifer is currently on the Atkins diet and is not consuming any carbohydrates. Would she still be able to make energy?
- YES
- Gluconeogenesis allows her to convert non-carbohydrate substances like pyruvate into glucose (reverse of glycolysis)
Many inborn errors of metabolism affect enzymes. What is an enzyme?
- Enzyme is a folded protein which can act on a substance and convert it into other products via catalytic activity
- e.g. Pepsin, which is an endopeptidase that breaks down proteins into smaller peptides.
List three factors that can influence enzyme function
- pH
Enzymes function within a narrow pH range. Changes in pH can make and break intra- and intermolecular bonds, leading to a change in shape of the enzymes, disrupting its bonding sites. - Temperature
Enzymes function best at their optimal temperature (37.5). If the temp. exceeds this, the enzyme structure will begin to denature (break down). This is due to the breakdown of the intra- and intermolecular bonds prompted by the increased kinetic energy. - Initial concentration of the substrate and enzyme
The reaction is dependant on the amount of substrate and enzyme. If the substrate concentration is high and that temp. and pH are kept constant, then the rate of reaction is proportional to the enzyme concentration (limited by the number of enzyme bonding sites).
How can a mutation in the DNA of an enzyme result in it becoming ineffective?
- When a gene mutation occurs, an amino acid may change in the sequence;
- Since protein folding (think tertiary structure) is highly dependent upon the amino acid sequence and composition, any tiny alteration could change the final structure, reaction or reaction sites.
- Thus the enzyme may lose its functionality.
Newborn screening programs are operated in each state to test for IEMs. They screen for variations in normal metabolites. Currently the NSW newborn screening tests screen for:
- PKU, phenylketonuria, which decreases metabolism of the amino acid phenylalanine, leading to intellectual disability;
- Congenital hypothyroidism, a thyroid hormone deficiency which leads to growth failure
- Cystic fibrosis, impacting the functions of lungs and digestive organs via impairing relevant secretion glands
- Galactosaemia, a condition in which the body is unable to use a sugar called galactose (monosaccharides of lactose)
- Aminoacidopathies, which is caused by the deficiency of an enzyme or transporter involved in amino acid metabolism
- Organic acidemias, an abnormal accumulation of (and usually toxic) organic acid metabolites
- Fatty acid oxidation defects
Two common IEM are phenylketonuria and cystinuria. Describe these disorders including the incidence rates:
- Phenylketonuria (PKU):
a. IEM which causes abnormal increase of phenylalanine in the blood
b. Phenylalanine is an essential amino acid (building block of proteins) that may be consumed by eating proteins and some artificial sweeteners
c. Phenylalanine in high concentration is harmful and may lead to intellectual disability etc. - Cystinuria:
a. autosomal recessive disease characterised by the formation of cystine (a type of amino acid) stones in the kidneys, bladder and ureters
b. Cystine usually enters the kidney and reabsorbed into the blood stream
c. However, people with Cystinuria have deficiency in absorption of cystine while letting it block the UT via forming cystine crystal and stones
Name and describe two examples of diseases, which can cause malabsorption and maldigestion. What are the metabolic implications of these GI tract disorders?
- Examples:
a. Coeliac disease - an autoimmune disease where the immune system reacts abnormally to gluten
b. Crohn’ disease - an inflammatory bowel syndrome, which causes abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition
c. Anorexia nervosa - If the patient is not absorbing the right nutrients or there’s an alteration in what can be absorbed in the GI tract, the patient may not be able to produce all of the substances and products required for metabolism
