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Carbohydrate Metabolism

Carbohydrate is complex structure that is broken down into simpler forms to aid digestion. This includes both mechanical and chemical mode of digestion. The mechanical form is that in the form mastication and churning that happens in the mouth and intestines, while the chemical means is with the help of salivary and pancreatic amylase.

During chewing and churning, larger food particles are broken down into smaller one, so that the enzymes could work effectively on them posing for the greater surface area present now. The larger polysaccharides are broken down further into disaccharides and monosaccharides.

The absorption of sugars is mainly in the duodenum and jejunum of pancreases.

Also, the monosaccharides formed via the processes till now, exist in two different forms mainly the hexoses and the pentoses. The primarily ones are absorbed more readily in the body than the later one. Some hexoses like glucose are absorbed via Na-glucose symport and some other like fructose via the process of facilitated diffusion, while the latter ones like pentoses are absorbed by simple diffusion. Insulin does not have any role to play in the absorption of the carbohydrates, rather it serves as a medium of carbohydrates as of now and to be released later when the body need is in need.

The major pathways of carbohydrate metabolism can be grouped into two, mainly oxidative and synthetic pathways. The oxidative pathways include glycolysis, HMP shunt and Uronic acid pathway, while the synthetic pathways are ones that include the oxidation of sugars other than glucose like galactose or fructose, glycogenesis, lipogenesis and synthesis of carbohydrates from non-essential fatty acids. For most of the pathways, glucose-6-phosphate works as the primarily substrate.

Glycolysis and TCA are the cycle that are used primarily for the oxidation process, while HMP shunt is alternate pathway. (chandel,2021)

Glycolysis is divided into 3 different stages, the primary energy investment phase, the secondary splitting phase and last energy generation phase. Initially enzymes like hexokinase and glucokinase kinase work on the hexose phosphates to split them into trioses. Here the glucose phosphate formed is isomerised into fructose-6-phosphate.The last one is the pay-off phase, addition of another phosphate molecule coverts the primary molecule to 1,3- biphosphoglycerate. Which is further converted to 3-phosphoglycerate, which is isomerised to 2-phosphoglycerate, which ends up as enolase. The NADH produced during this process passes through the electron transport chain, producing ATPs. The end products of glycolysis in aerobic conditions is pyruvate and those in the anaerobic condition is lactic acid, so for the former conditions 7 ATP are produced while for the latter one’s only 2 ATPs are obtained.

The pyruvate so produced is converted to Acetyl CoA which then enters the TCA cycle, here a total of 32 ATP +6 H2O+6 CO2 are produced. Oxygen does not play any significant part here. But oxaloacetic acid play the role of primary substrate here.

Hexose monophosphate shunt, it has two main phases the oxidative phase and the non- oxidative phases. This particular pathway is not dependant on oxygen and is considered to be more in role for producing pentoses. It take place in the cytosol.Here the main molecule involved is ribose-5- phosphate. The importance of pentoses lie in the production of nucleic acids and thus this cycle does not produce any ATP i.e. ATP is neither produced nor used in HMP pathway. The NADPH produced in this cycle has multiple uses, like biosynthesis of fatty acids and steroids, antioxidant reactions to produced In body, phagocytosis, and detoxification of drugs via.

Gluconeogenesis takes place in the cytosol only. And is the process in which glucose if formed from non-carbohydrate sources. Here more importantly, pyruvate carboxylase converts pyruvate to OAA wheres as PEP carboxylase kinase converts OAA to PEP in the cytosol, thus acting as a reversal reaction. This reaction produces utilises 2 pyruvate,2ATP, 2GTP,2H+,6 H2o to give one molecule of glucose,2NAD+,2ADP,2GDP and 6 molecules of phosphates and hydrogen ion.

Glycogenesis -It is the synthesis of glycogen from glucose ,glycogen being the main storage form in animals. It also takes place in cytosol. This reaction as uses glucose in it’s hexose form but glucose 1 –phosphate and requirement of primer to intiate glycogenesis.

Input- if n molecules of glucose are used along with 2 ATP

Output- n+1 glucose molecules with ADP and phosphates

Oxidative phosphorylation-is the process of generating ATP from ADP and Pi molecules coupled with the steps of ETC. this process takes place in the inner membrane of the mitochondria, where the last complex, complex V is located.

ETC- takes place in the mitochondria and here carbohydrates, fats and proteins are oxidised to produce NADH and FADH2 . Here mitochondrial complex generate ATP based on the difference in redox potential.

Lipogenesis- It is the process of conversion of Acetyl CoA to the form of triglyceride for the purpose of storage. Acetyl CoA is formed from the end product of glycolysis. Conversion of Acetyl-CoA to Malonyl CoA and it’s conversion to palmitate are the main reactions of the process. (Sanders,2016)

TASK B

Diabetes Mellitus is a lifestyle disease. The only method of glucose uptake in the body is not through carbohydrates that we eat in daily diet, but also pathways like gluconeogenesis and glycogenolysis that play a significant role in in producing glucose as substate for the oxidative processes to produce energy. The excess amount of glucose thus present is our body is regulated by insulin, that converts it into storage form, which is later converted back glucose by glucagon as per the body requirements.

Diabetes mellitus is two types mainly, in which the type 1 denotes the due to autoimmune activity , pancreas cells are destroyed, thus rendering them incapable of producing insulin, while in type 2, due to certain factors like genetics, obesity, pregnancy etc. the body cells develop a weak affinity for insulin or that ample amount of insulin is present in the body but, the body tissues cannot utilise, leading to increased blood sugar levels and other complications.

A diet that is high in carbohydrates, usually results in steep peak in the blood sugar levels in the post prandial time period, but due to lowered insulin sensitivity, organs cannot utilise the insulin, neither is stored. Once it crosses 200 mg/dl it is excreted out in the urine, also causing loss of large amount of water with it. Since glucose and Na works via a symport, electrolytes are also lost, which may cause dehydration. (Ojo,2019)

On the other hand the body cells are still starving, since there energy demands are not being met, so the body choses other pathways, that uses fats and proteins (amino acids) or breaks the already preserved body mass(glycogen) to generate glucose-6 phosphate as the substrate. The main area for gluconeogenesis is liver. In the process the muscle mass is broken down (protein and adipose tissue) but lot of glycogen stored is converted into fat, but still the glucose so produced will not be utilised by the body due to lower insulin sensitivity and the patient will experience fatigue on a more prominent basis.

A carbohydrate rich puts more pressure on the endocrine system to meet up with the needs of the high sugar levels. On the other hand, taking meals that have sustained released carbohydrates and protein and fats, maintains a sustained release of glucose rather than a sharp peak, and no sudden complications develop. Also, processes like exercises or taking insulin along with diet modification, increases the cellular sensitivity to insulin, and though there is no permanent solution to this, but these steps drastically increase the longevity of the patient. (Rivellese,2012)

There are a lot of complications related to diabetes type 2, most common one is hyperosmolar hyperglycaemic state, which is due to relative deficiency of insulin.

References

Chandel N. S. (2021). Carbohydrate Metabolism. Cold Spring Harbor perspectives in biology, 13(1), a040568. https://doi.org/10.1101/cshperspect.a040568

Ojo O. (2019). Dietary Intake and Type 2 Diabetes. Nutrients, 11(9), 2177. https://doi.org/10.3390/nu11092177

Rivellese, A. A., Giacco, R., & Costabile, G. (2012). Dietary carbohydrates for diabetics. Current atherosclerosis reports, 14(6), 563–569. https://doi.org/10.1007/s11883-012-0278-4

Sanders, F. W., & Griffin, J. L. (2016). De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biological Reviews of the Cambridge Philosophical Society, 91(2), 452–468. https://doi.org/10.1111/brv.12178, F. W., & Griffin, J. L. (2016).

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