Cholesterol is synthesized in the body and obtained through diet. It has important functions but excess can promote atherosclerosis. Cholesterol synthesis occurs mainly in the liver and involves four stages. The rate-limiting enzyme HMG-CoA reductase is regulated by phosphorylation/dephosphorylation and repression/derepression. Cholesterol levels in cells are regulated by LDL receptor uptake and catabolism to bile acids. High LDL and triglycerides increase atherosclerosis risk while high HDL is protective. Risk factors like these are addressed through dietary and drug measures like statins that lower cholesterol synthesis.
Glycogenolysis, process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. These slides will provide you detail explanation of Glycogenolysis.
Lipid metabolism is the synthesis and degradation of lipids in cells.
It involves the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes.
In animals, these fats are obtained from food or synthesized by the liver.
Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids.
Glycogenolysis, process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. These slides will provide you detail explanation of Glycogenolysis.
Lipid metabolism is the synthesis and degradation of lipids in cells.
It involves the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes.
In animals, these fats are obtained from food or synthesized by the liver.
Lipid metabolism entails the oxidation of fatty acids to either generate energy or synthesize new lipids from smaller constituent molecules. Lipid metabolism is associated with carbohydrate metabolism, as products of glucose (such as acetyl CoA) can be converted into lipids.
Cholesterol is the major sterol in the animal tissues.
Cholesterol is present in tissues and in plasma either as free cholesterol or as a storage form, combined with a long-chain fatty acid as cholesteryl ester.
In plasma, both forms are transported in lipoproteins
removed from tissues by plasma high-density lipoprotein (HDL) and transported to the liver, where it is eliminated from the body either unchanged or after conversion to bile acids in the process known as reverse cholesterol transport
lipoproteins transfer lipids such as triacylglycerol, cholestryl ester, fat soluble vitamins in the body. there are 5 categories of lipoproteins which includes chylomicrone, VLDL, IDL, LDL and HDL. LDL-cholesterol is called bad cholestrol while HDL-cholesterol is called good cholesterol.
Multiple Choice Questions with Explanatory Answers on Chemistry of Carbohydrates for Medical, Biochemistry and Biology students - Chapter 1 of Multiple Choice Questions in Biochemistry by RC Gupta
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
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The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Metabolism of cholesterol
1. Metabolism of Cholesterol
R. C. Gupta
Professor and Head
Department of Biochemistry
National Institute of Medical Sciences
Jaipur, India
2. Cholesterol can be synthesized only by
animals
It is present in all animal cells
It circulates in blood as a component of
various lipoproteins
3. Cholesterol serves many important functions
It is required for the formation of membranes,
steroid hormones, vitamin D3, bile salts etc
An excess of cholesterol in the body can be
harmful as it promotes atherosclerosis
4. Cholesterol is both taken in diet and is
synthesized in the body
Endogenous synthesis is inversely
related to the dietary intake
A high intake decreases the endogenous
synthesis
5. The major sites for cholesterol synthesis
in human beings are liver, skin and
intestinal mucosa
All the reactions occur in cytosol except
for a hydroxylation reaction which occurs
in endoplasmic reticulum
6. Acetyl CoA provides all the carbon atoms
for cholesterol synthesis
ATP is required as a source of energy
NADPH, molecular oxygen and micro-
somal hydroxylase system are required
for a hydroxylation reaction
7. A carrier protein is required to bind some
of the intermediates
The carrier protein is ‘squalene and sterol
carrier protein’
8. The reactions of cholesterol synthesis
can be divided into four stages:
• Conversion of acetyl CoA into six-
carbon compound, mevalonate
• Conversion of mevalonate into five-
carbon isoprenoid units
• Conversion of six isoprenoid units into a
30-carbon compound, squalene
• Conversion of squalene into cholesterol
9. Two molecules of acetyl CoA react to form
acetoacetyl CoA
Another acetyl group is added to form b-
hydroxy-b-methylglutaryl CoA (HMG CoA)
HMG CoA is reduced to mevalonate
Reactions of the first stage
10.
11. Mevalonate undergoes three successive
phosphorylations to form mevalonate-3-
phospho-5-pyrophosphate
The latter is converted into two types of
isoprenoid units
The units are isopentenyl pyrophosphate
and 3,3-dimethyl allyl pyrophosphate
Reactions of the second stage
12.
13. Two isoprenoid units form geranyl pyro-
phosphate, a 10-carbon compound
Geranyl pyrophosphate and one isoprenoid
unit form15-carbon farnesyl pyrophosphate
Two molecules of farnesyl pyrophosphate
form 30-carbon squalene
Reactions of the third stage
14.
15. Squalene is oxidized to squalene oxide
Squalene oxide is cyclized to lanosterol
By a series of reactions, lanosterol is
converted into cholesterol
Reactions of the fourth stage
16.
17. HMG CoA reductase (HMGR) is the
regulatory enzyme
It is regulated by multiple mechanisms
Both the activity and the amount of the
enzyme can be regulated
Regulation
18. HMG CoA reductase exists in a:
▪ Dephosphorylated form (active)
▪ Phosphorylated form (inactive)
AMP-activated protein kinase (AMPK)
phosphorylates the enzyme
Protein phosphatase 1 (HMGR phos-
phatase) dephosphorylates the enzyme
19. Activity of protein phosphatase 1 (PP1) is
regulated by protein kinase A
Protein kinase A (PKA) is activated by
cAMP
Thus, hormones that affect cAMP concen-
tration regulate cholesterol synthesis
20. Glucagon increases cAMP concentration,
and activates PKA
PKA phosphorylates a regulatory subunit of
protein phosphatase 1
This results in inhibition of protein
phosphatase 1
HMGR remains inactive and cholesterol
synthesis is decreased
21. Insulin causes a decrease in cAMP
concentration
As a result, PKA remains inactive; protein
phosphatase 1 is not inhibited
Protein phosphatase 1 dephosphorylates
inactive HMGR to its active form
Cholesterol synthesis is increased
22.
23. Cholesterol synthesis is also regulated by
repression and derepression
Excess of cholesterol represses the
synthesis of HMG CoA reductase
This decreases cholesterol synthesis
Decreased cholesterol level derepresses
the synthesis of HMG CoA reductase
24. HMGR contains a sterol-sensing domain
(SSD) which monitors sterol level in the cell
Increased sterol levels cause ubiquitination
of HMGR
Ubiquitinated HMGR is rapidly degraded by
proteasome
This decreases cholesterol synthesis
25. The entry of cholesterol into cells is also
precisely regulated
LDL is the major carrier of cholesterol
to extra-hepatic tissues
LDL is taken up by the cells with the help
of LDL receptors
26. LDL receptors are present on the cell
membrane
Binding of LDL to its receptor is followed
by receptor-mediated endocytosis
Both LDL and its receptor enter the
cell
27. As LDL enters the cell, the number of LDL
receptors on the cell decreases
Thus, the receptor is down-regulated
Downregulation of the receptor decreases
further entry of LDL in the cell
28. The major pathway for catabolism of
cholesterol is its conversion into bile acids
and bile salts in liver
Cholesterol is first converted into 7-a-
hydroxycholesterol by 7-a-hydroxylase
7-a-Hydroxylase is a part of microsomal
hydroxylase system
Catabolism of cholesterol
29.
30. Most of the 7-a-hydroxycholesterol
is converted into cholic acid
Cholic acid can combine with:
Glycine to form glycocholic acid
Taurine to form taurocholic acid
31. Some of the 7-a-hydroxycholesterol is
converted into chenodeoxycholic acid
This can combine with glycine to form
glycochenodeoxycholic acid
It can combine with taurine to form tauro-
chenodeoxycholic acid
32.
33. Glycocholic acid, taurocholic acid, glyco-
chenodeoxycholic acid and taurocheno-
deoxycholic acid are primary bile acids
Their Na+ and K+ salts are known as bile
salts
Bile salts are formed in liver, and are
excreted through bile into the intestine
34. Most of the bile salts entering the
intestine are reabsorbed into portal blood
These are brought to liver, and are re-
excreted into the intestine by the liver
This is known as enterohepatic circulation
of bile salts
35. Intestinal bacteria convert unabsorbed bile
salts into secondary bile acids and sterols
Deoxycholic acid and lithocholic acid are the
main secondary bile acids
Coprostanol is the main sterol formed from
bile salts
These are excreted in the faeces
36.
37. Atherosclerosis is a condition in which
cholesterol and some other substances are
deposited in the walls of blood vessels
Lumen of the affected vessel is narrowed
This impedes blood flow and decreases the
supply of blood to the affected organ
Serum lipids and atherosclerosis
39. Coronary arteries are affected most
commonly leading to coronary artery
disease (CAD)
Involvement of cerebral arteries causes
cerebral thrombosis
Arteries supplying blood to lower limbs
may be affected resulting in peripheral
vascular disease
40. Risk of CAD is increased by a number of
conditions and habits
These conditions and habits are known
as coronary risk factors
Some of the coronary risk factors are
modifiable but others are not
41. The modifiable coronary risk factors
include:
• Dyslipidaemia
• High blood pressure
• Diabetes mellitus
• Obesity
• Smoking
• Lack of physical activity
• Unhealthy diet
• Stress
42. The association between dyslipidaemia
and CAD has been proved in many studies
There is a positive correlation between
high serum cholesterol and CAD
The risk is modestly increased by elevated
serum triglycerides
43. Cholesterol is present in plasma mainly in
LDL and HDL
It is elevated LDL-cholesterol which
increases the risk of CAD
High HDL-cholesterol has a protective
effect
45. Measurements of apo A-I and apo B in
plasma may also be informative
A rise in apo B level indicates an
increased risk of CAD
A rise in apo A-I indicates a decreased
risk
46. Lp (a) is another risk factor for CAD
It is an abnormal variant of LDL
Lp (a) is formed when apo (a) forms a
disulfide bond with apo B-100 of LDL
Apo (a) is an apolipoprotein having a
structural resemblance with plasminogen
47. Apo (a) competes with plasminogen for
binding to fibrin
It decreases fibrinolysis
Some people have an elevated level of
plasma Lp (a)
Levels above 30 mg/dl increase the risk
of premature CAD
48. Control of coronary risk factors requires:
Dietary
measures
Pharmacological
measures
49. The dietary measures to control
coronary risk factors include:
Reduction in fat intake
Reduction in cholesterol intake
Replacement of SFA with PUFA
Dietary measures
50. Pharmacological measures include use of
drugs that decrease serum cholesterol
Common hypocholesterolaemic drugs are:
(i) bile acid-binding resins, (ii) nicotinic acid
and (iii) inhibitors of HMG CoA reductase
A fourth class, fibric acid derivatives, is more
effective in reducing serum triglycerides
Pharmacological measures
51. Bile acid-binding resins include colestipol
and cholestyramine
They bind bile acids in the intestine
preventing their reabsorption
Enterohepatic circulation of bile acids is
interrupted
52. Decreased reabsorption necessitates
increased synthesis of bile acids from
cholesterol in the liver
Thus, more cholesterol is diverted to bile
acid synthesis resulting in a decrease in
serum cholesterol level
53. Nicotinic acid (niacin) in large doses
decreases the level of serum cholesterol
Mechanism of action of nicotinic acid is
unclear
It decreases the secretion of lipoproteins
containing apo B-100 from liver
54. Statin family of drugs competitively
inhibits HMG CoA reductase
This decreases endogenous synthesis of
cholesterol
Statins are the most effective hypo-
cholesterolaemic drugs
They also cause a modest decrease in
serum triglycerides
55. Lovastatin and mevastatin are the oldest
members of the statin family
The newer members include atorvastatin,
fluvastatin, simvastatin etc
56. Fibric acid derivatives include clofibrate,
fenofibrate, gemfibrozil etc
They activate lipoprotein lipase which
hydrolyses the triglycerides present in the
lipoproteins
VLDL and triglyceride concentrations are
decreased
Cholesterol is modestly decreased