User:Jakedennis/LHF-II

Overview

Bushmaster snake

LHF-II, short for Lachesis muta Hemorrhagic Factor II, is a prominent enzyme found in the venom of the Southern American bushmaster snake, scientifically known as lachesis muta. This snake is indigenous to the tropical rainforests of Central and South America and is one of the largest venomous snakes in the Western Hemisphere. LHF-II is one of two hemorrhagic metalloproteinases, the other being LHF-I, isolated from the venom of this snake species. Its primary functions include proteolytic degradation of extracellular matrix components, induction of edema, and, to a lesser extent, localized hemorrhage. While it may not be the sole contributor to the toxic effects of bushmaster snake venom, LHF-II plays a significant role in the local tissue damage observed in snakebite envenomations, which can have serious consequences for both prey and potential predators. Further research continues to shed light on the complex mechanisms underlying the action of LHF-II and its interactions within the venom's toxic arsenal.

Classification:

LHF-II, also known as mutalysin II, has the following Enzyme Commission (EC) number: 3.4.24.B37. This is a preliminary number supplied by the BRENDA enzyme database, a site run by the Leibniz Institute DSMZ in Germany. The EC number can be broken down as such:

The first number, 3, indicates that LHF-II is a hydrolase, meaning it uses water to cleave bonds in substrates in a process called hydrolysis. The second number, 4, indicates that LHF-II is a hydrolase that acts on peptide bonds specifically, in this case usually degrading peptide bonds of molecules in the cellular matrix of an organism that has been envenomated. The third number, 24, indicates that LHF-II is a matrix metalloprotease (MMP). This means it is a molecule that degrades proteins (hence "-protease") in the cellular matrix (hence "matrix") and whose catalytic mechanism involves a metal (hence "metallo-"). The last number, B37, distinguishes LHF-II specifically as a compound. As this EC number is only preliminary, it is not found in all works that reference the compound.

LHF-II has also been referred to as an SVMP, or snake venom metalloprotease. SVMPs encompass a wide range of multi-domain proteins that possess various biological functions, including the capacity to trigger hemorrhage, break down fibrinogen and fibrin through proteolysis, induce apoptosis, and hinder platelet aggregation. As a result of these functions, SVMPs are accountable for numerous recognizable pathological manifestations in cases of snakebite envenomations.

Hemorrhagic Activity:

Despite its robust proteolytic activity, LHF-II is categorized as a hemorrhagic metalloproteinase with relatively low hemorrhagic potency compared to some other snake venom enzymes. Hemorrhage refers to the escape of blood from the circulatory system into surrounding tissues, resulting in bleeding. When LHF-II is introduced into the body, it can cause localized hemorrhage, but it generally requires higher doses of the enzyme to induce significant bleeding compared to other snake venom components. Intriguingly, this hemorrhage is typically characterized by microhemorrhages in capillary vessels and small venules rather than larger blood vessels.

Chemical Structure:

LHF-II is a complex enzyme, with its sequence consisting of over 200 amino acids. Its full sequence can be found in a paper written by Sanchez, Diniz, and Richardson in 1991 titled "The complete amino acid sequence of the haemorrhagic factor LHFII, a metalloproteinase isolated from the venom of the bushmaster snake (Lachesis muta muta)."

Proteolytic Activity:

Insulin structure modeling amino acids

LHF-II is primarily recognized for its potent proteolytic or protein-breaking capabilities. It possesses an ability to cleave specific peptide bonds within proteins, particularly those found in extracellular matrix components. These include proteins like type IV collagen, laminin, and fibronectin. By cleaving the bonds in these essential structural proteins, LHF-II contributes to the degradation of the extracellular matrix, which forms the structural framework of tissues. This matrix degradation is associated with local tissue damage, including hemorrhage, edema (swelling), and mild myonecrosis (muscle cell death). This enzymatic activity makes it a key player in the venom's ability to disrupt and damage the tissues of its prey or potential threats, such as small mammals and other animals.

As an example, one such cleavage reaction occurs with insulin molecules, wherein LHF-II cleaves the Ala14-/-Leu15 bond of insulin B-chain very rapidly and the Phe24-/-Phe25, His10-/-Leu11 and His5-/-Leu6 bonds more slowly. This catabolism of insulin molecules can result in insulin deficiency, which leads to further complications such as hyperglycemia and subsequently weight loss, tiredness, impaired consciousness level, hyperventilation due to ketoacidosis, and even coma. Although this may not be the most detrimental effect induced by envenomation by a Southern American bushmaster, it does directly exhibit one of the ways in which LHF-II acts to impair victims of the deadly snake.