Question

Q4 What is the effect on the tca cycle when muscle mitochondria containing pyruvate dehydrogenase complex is treated with (a) fatty acids or (b) calcium Q5 Why are mutations in citrate synthase very rare?

Answer 1

In mammals, glucose in excess is stored as glycogen in liver. During nutrient deprivation and maintenance of internal body temperature also known as homeostasis, there are metabolic pathways which are tissue specific and ensure metabolism of glucose and lipids with rearrangement of glucose and fatty acid molecules in skeletal muscles and liver, glucogenic precursors are obtained from lactate and alanine, which are rendered by muscle to liver directing the synthesis of glucose. PDH is stimulated by catalyzing with the help of four different enzymes such as PDK1, PDK2, PDK3, PDK4. The increase in the cellular energy, there is enhancement of these four enzymes triggering the production of NADH and ATP which are reservoirs of energy.When the cellular energy is low, ADP , NAD+ and coASh levels increase.

As we age, cellular oxidation increases and as a result metabolic disorders start manifesting. The progressive degenerative disease of ageing results from the lack of antioxidants which decrease eventually. This may lead to various manifesting ailments such as hearing loss. However, mutations in the citrate synthase are rare because in a bacterial population which was grown in the laboratory adapts itself to the environment with genetic changes. They obtained source of food molecule from citrate, which paved the way for mutations by the gene gltA encoding the enzyme citrate synthase. The mutation occurred when bacteria was unable to use citrate as a food source, and the ability of the bacteria to use the citrate as a result of genetic mutation inhibited the transport of citrate. However, further mutations enabled bacteria consume food from citrate thus decreasing use of citrate synthase activity resulting in less mutations.