Biosynthesis of Protein : Translation Process Video

The translation process is divided into three steps:

Initiation: When a small subunit of a ribosome charged with a tRNA+the amino acid methionine encounters an mRNA, it attaches and starts to scan for a start signal. When it finds the start sequence AUG, the codon (triplet) for the amino acid methionine, the large subunit joins the small one to form a complete ribosome and the protein synthesis is initiated.

Elongation: A new tRNA+amino acid enters the ribosome, at the next codon downstream of the AUG codon. If its anticodon matches the mRNA codon it basepairs and the ribosome can link the two aminoacids together.(If a tRNA with the wrong anticodon and therefore the wrong amino acid enters the ribosome, it can not basepair with the mRNA and is rejected.) The ribosome then moves one triplet forward and a new tRNA+amino acid can enter the ribosome and the procedure is repeated. 

Termination: When the ribosome reaches one of three stop codons, for example UGA, there are no corresponding tRNAs to that sequence. Instead termination proteins bind to the ribosome and stimulate the release of the polypeptide chain (the protein), and the ribosome dissociates from the mRNA. When the ribosome is released from the mRNA, its large and small subunit dissociate. The small subunit can now be loaded with a new tRNA+methionine and start translation once again. Some cells need large quantities of a particular protein. To meet this requirement they make many mRNA copies of the corresponding gene and have many ribosomes working on each mRNA. After translation the protein will usually undergo some further modifications before it becomes fully active.

Lipoprotein Metabolism : Animation video

Composition of Lipoproteins:

1. Consists of non-polar core (Mainly Triglycerides and cholesteryl esters)
2. A single surface layer of amphipathic phospholipids and cholesterol
3. Protein moiety are known as Apoprotein or Apolipoprotein
4. Protein and lipid contents vary

Synthesis of Chylomicrons and VLDL: 

Metabolism of Chylomicrons:

• Synthesised in intestine
• Transport TAG (Triacylglycerol) to tissues and deliver remaining cholesterol & cholesterol ester to the liver.

Metabolism of VLDL, LDL and IDL:

• VLDL is synthesised in liver and converted to LDL which contain an increased proportion of cholesterol & cholesteryl ester (due to loss of TAG).
• Transport TAG and cholesterol from liver to tissues.
• Cholesterol in LDL referred to as “bad cholesterol” since LDLs are implicated in atherosclerosis

Metabolism of HDL (High Density Lipoprotein):

• HDL carries “used” cholesterol (as CE) back to the liver. Also donate some CE to circulating VLDL for redistribution to tissues.
• HDL taken up by liver and degraded. The cholesterol is excreted as bile salts or repackaged in VLDL for distribution to tissues.
• Cholesterol synthesis in the liver is regulated by the cholesterol arriving through HDL (and dietary cholesterol returned by chylomicron remnants).
• Cholesterol (CE) in HDL is referred to as “good cholesterol”.

Pathophysiology of Diabetic Ketoacidosis : Animation

When the rate of synthesis of ketone bodies exceeds the rate of utilization, their concentration in blood increases, this is known as ketonemia. This is followed by ketonuria – excretion of ketone bodies in urine. The overall picture of ketonemia and ketonuria is commonly referred to as ketosis.

Mechanism: 

1. Hyperglycaemia occurs due to decreased glucose uptake in fat and muscle cells due to insulin deficiency Lipolysis in fat cells now occurs promoted by the insulin deficiency releasing 
2. Free fatty acids (FFA) into the blood which provide substrate to the liver 
3. A switch in hepatic lipid metabolism occurs due to the insulin deficiency and the glucagon excess, so the excess FFA is metabolised resulting in excess production of acetyl CoA 
4. The excess hepatic acetyl CoA (remaining after saturation of TCA cycle) is converted to ketone bodies which are released into the blood 
5. Ketoacidosis and hyperglycaemia both occur due to the lack of insulin and the increase in glucagon and most of the clinical effects follow from these two factors 

Summary:

1.    ↓ Insulin, ↑Glucogon (glycogen à glucose) -  Glucose 500-700 mg/dl 2.    Glucose-derived osmotic diuresis 3.    ↑ Glucagon -  ↑ FFA esterfied à ketone bodies à acidosis

Diagnostic tests:

1. Blood glucose greater than 250 mg/dL 
2. Blood pH less than 7.3 
3. Blood bicarbonate less than 15 mEq/L 
4. Ketones present in blood (exceeds 90 mg/dl) 
5. Ketones excreted in urine exceeds 5000 mg/24 hrs 

Signs and Symptoms:

1. Kussmal's respiration 
2. Fruity odor of breath 
3. Nausea and abdominal pain 
4. Dehydration 
5. Lethargy 
6. Coma 
7. Polydipsia, polyuria, polyphagia