The metabolism, glycolysis and gluconeogenesis (Other macros conversion to carbohydrates)

Macronutrients include protein, carbohydrates and fat, and they are the most important nutrients in the body, making up the bulk of calorie consumption. Protein and carbohydrates are typically 4 kcal per gram, while fat is typically 9 kcal per gram due to having more hydrocarbon bonds which store much more chemical energy. However, slight changes in the chemical structure of protein, carbohydrates and fat can make this figure not exact. 

1 kilocalorie is made up of 1000 calories, despite what the food labels say on the packaging they are almost always talking about kilocalories (kcal) and not calories. 1 kcal is enough to heat 1 kg of water from 0°C to 1°C, the thermal energy is created when the energy from food is converted to chemical energy in the form of ATP and the ATP is used in energy consuming processes forming thermal energy.

For macronutrients to be used for energy they must be first broken down to small molecules, this means polysaccharides into monosaccharides, protein into amino acids and fats into fatty acids and glycerol.

The monosaccharide glucose can undergo the process of glycolysis to form ATP. The equation for glycolysis is as follows:

Glucose + 2 NAD+ + ADP + 2 P > 2 pyruvate + 2 NADH +2 ATP

This process requires many steps and many enzymes. Many substances are created during this process but key substances in the process of glycolysis is:

Glucose >  Glucose-6-phosphatase > Fructose-1,6-bisphosphate > Pyruvate

I label these as key substances in the steps of glycolysis because these steps are not easily reversible, such as many other steps in the process of glycolysis.

In this process NAD+ is reduced to NADH which can be oxidised in the electron transport chain to form more ATP.

With the help of oxygen the pyruvate produced in glycolysis can enter the mitochondria in the cell and be used for oxidative metabolism. Pyruvate once it has entered the mitochondria will convert into Acetyl-CoA which can enter a series of reactions known as the krebs cycle with the help of oxaloacetate, at the end of this cycle oxaloacetate will be formed along with, 3 NADH, 1 FADH2, 2 CO2 and 2 ATP. The NADH and FADH2 produced in the krebs cycle, as well as the NADH produced in glycolysis can travel to the electron transport chain embedded in the intermitochondrial membrane where they donate an electron which travels along the chain and generates the ability to transport hydrogen ions from NADH and FADH2 across the intermitochondrial membrane and into the intermembrane space. The buildup of hydrogen ions in the intermembrane space will cause the hydrogen ions to diffuse back into the mitochondrial matrix through transporters known as ATP synthase which produces 34 ATP.

During the process of glycolysis of glucose metabolism 2 ATP is needed and 4 ATP is produced, leaving a net 2 ATP for the cell to use.

The monosaccharide fructose can also join the process of glycolysis at a later stage somewhere between fructose-1,6-bisphosphate and pyruvate, in this process 2 ATP is used in different processes to glucose glycolysis but 4 ATP is also produced in the same way as glucose glycolysis, leaving a net 2 ATP for the cell to use, primarily in the liver due to the types of enzymes contained in the liver.

The monosaccharide galactose can also join the process of glycolysis at a very early stage in the form of glucose-6-phosphate, in this process 2 ATP is used, 1 of which in a different process to glucose glycolysis but 4 ATP is also produced in the same way as glucose glycolysis, leaving a net 2 ATP for the cell to use, again galactose is primarily metabolised in the liver due to the more appropriate enzyme types.

Gluconeogenesis is the name given to the processes which cause the conversion of substances to glucose, primarily in the liver. 

The products of protein and triglycerides can undergo the process of gluconeogenesis. In fact this process is so important even the other monosaccharides fructose and galactose can undergo this process.

The process of gluconeogenesis is heavily linked to the process of glycolysis. To understand the process of gluconeogenesis it is important to recall the 4 key substances of glycolysis:

Glucose >  Glucose-6-phosphatase > Fructose-1,6-bisphosphate > Pyruvate

For a substance to form glucose it must jump into one of these key steps of glycolysis and move backwards to form glucose, where it can then leave the cell.

The monosaccharide galactose joins the process of glycolysis in the form of glucose-6-phosphatase, for glucose-6-phosphatase to form glucose it must enter the sarcoplasmic reticulum and convert into glucose.

The monosaccharide galactose joints the process of glycolysis somewhere between pyruvate and fructose-1,6-bisphosphate, here it is easy for the substance to convert to fructose-1,6-bisphosphate and from here an enzyme is required to convert the substance to glucose-6-phosphatase, and just like in the case of galactose this substance can enter the sarcoplasmic reticulum and convert to glucose.

Triglycerides get broken down into glycerol and fatty acids in the body. Glycerol can jump into the process of glycolysis and be reversed into glucose in the form of fructose-1,6-bisphosphate. Fatty acids jump into a later stage of the metabolism after glycolysis in the form of Acetyl-CoA. 

Protein gets broken down into amino acids in the body. Amino acids can jump into the process of the metabolism through converting into pyruvate, Acetyl-CoA or as a substance which is part of the krebs cycle. Pyruvate in the process of gluconeogenesis can form oxaloacetate, which is then converted into malate. Malate can jump into the processes of glycolysis between fructose-1,6-bisphosphate and pyruvate where it can go back to form fructose-1,6-bisphosphate. Interestingly oxaloacetate can convert into pyruvate, often during low energy periods where it can then form Acetyl-CoA. 

It is important to note that glycolysis is the name given to the process of glucose breakdown and I have only used the term glycolysis when referring to the breakdown of triglycerides or protein to form ATP to make the processes and the relationship more easily understandable.

Lipogenesis (Other macros conversion to fat)

Once the liver has converted enough substances into glucose the liver will begin to store this glucose in the form glycogen in a process known as glycogenesis. If the livers glycogen stores are full it can begin the process of lipogenesis.

For the purpose of lipogenesis it is important to note the first 3 substances of the krebs cycle. First oxaloacetate and Acetyl-CoA forms citrate, this can be converted into isocitrate, this can be converted into Alpha-ketoglutarate. The enzyme responsible for the conversion of isocitrate into Alpha-ketoglutarate is inhibited by ATP, Isocitrate can then convert back into citrate. Citrate can pass through the mitochondrial membrane where it is converted into oxaloacetate and Acetyl-CoA. The oxaloacetate produced is then converted into malate, this also stimulates the conversion of NADP+ into NADPH, The NADPH produced here, and NADPH produced in the pentose phosphate pathway can be used to form fatty acids. The Acetyl-CoA produced is then converted with CO2 into Malonyl-CoA, the enzyme responsible for this process is regulated via hormonal or allosteric factors. Insulin is a hormonal factors which helps stimulate this process. Cortisol, glucagon, epinephrine and norepinephrine are all hormonal factors which helps inhibit this process. Citrate is an allosteric factor which help stimulate this process. Long chain fatty acid coenzyme A is an allosteric factor which helps inhibit this process, this means that when fatty acids are abundant in the liver this process is not as stimulated.  Malonyl-CoA can travel to and inhibit the CPT-1 protein embedded in the mitochondrial membrane, this stops the translocation of fatty acids into the mitochondria in order to inhibit the breakdown of fatty acids and therefore increase their accumulation through the process of lipogenesis.

NADPH and Malonyl-CoA undergo a very long process through the fatty acid synthase type 1 enzyme in order to form a 16 carbon fatty acid chain, in this process 1 acetyl-coa, 8 malonyl-coa and 2 NADPH will go into this process, and 1 H2O and 8 CO2 will be lost.

Glycerol-3-phosphate is needed for the purpose of lipogenesis. Glycerol-3-phosphate can be converted from glycerol or it can be synthesised by the enzyme DHAP when combined with NADH. DHAP is an enzyme formed during the breakdown of fructose-1,6-bisphosphate during the process of glycolysis. Glycerol and 3 fatty acid tails can combine to form a triglyceride, also known as triacylglycerol (TAG) or a glycerol and 2 fatty acid tails can form a phospholipid.

Triglycerides, phospholipids and apoproteins can combine in the Golgi apparatus of liver cells to form very low-density lipoprotein (VLDL). VLDL travels in the bloodstream where it can encounter lipase which will release the triglycerides where they can enter cells for storage or to be used for energy. VLDL is broken down to IDL, LDL then finally HDL as the ratio of fat to lipoproteins decrease.

Notes on other macros conversion to protein

Proteins and fats can form glucose, and carbohydrates and proteins can form triglycerides, however carbohydrates and fats can not form protein, they can only simply supply the energy to conduct protein synthesis in the form of ATP. Protein is therefore often considered the most important macronutrient as it is essential to consume a large quantity of protein in the diet. Although fat is also essential due to the essential fatty acids, Omega-3 and Omega-6, and fat soluble vitamins.