DEPARTME

NT OF BIOCHEMISTRY

Nutrition, Metabolism & Gastro-Intestinal System

Name: John.M.Mwale

Student ID: 190102482

Programme: Bachelors of Medicine and Bachelors Surgery (MBChB)

Course/Code: GIT 301- Biochemistry

Lecturer: Mr Shandele Ginnethon

Group number: One (1)

Assignment Number: One (1) Due date: 13.04.2022

QUESTION ONE: [50 marks]

The human body naturally regulates blood glucose levels as a part of metabolic homeostasis in order to
maintain blood sugar levels between 70 -100 mg/dL approximately. However, this tight regulation of
blood sugar levels is usually met with several metabolic and hormonal setbacks.

(a) Elucidate the mechanisms of hormonal control that the body uses to maintain stable blood glucose
levels. [10]

(b) Discuss the role of carbohydrate metabolic pathways in regulation of blood sugar levels. [15]

(c) Describe the relationship between hyperglycemia and hyperlipidemia. How does hyperlipidemia lead
to hyperglycemia? Explain the role of HMG-CoA reductase lipid metabolism disorders. [15]

(d) Diabetic ketoacidosis (DKA) is an acute and dangerous complication of Diabetes Mellitus. Using your
knowledge on metabolic pathways, explain how DKA is brought about and suggest the possible
management of the same. [10]
a) Mechanisms of hormonal control that the body uses to maintain stable blood glucose levels.

The plasma glucose level at an instant depends on the balance between glucose entering and leaving
the extracellular fluid. Hormones will make this balance possible. Insulin and Glucagon are the major
hormornes responsible for maintaining blood glucose levels. There are other minor hormones which
help to maintain blood glucose levels and these are growth hormornes, adrenocorticotropic, cortisol,
glucocorticoids, epinephrine and thyroxine hormones .All these hormornes are divided into either
Hyperglycemic or hypoglycemic hormones.

Hypoglycemic Hormones

1)Insulin

The rise in the blood glucose level stimulates the secretion of insulin by beta cells of islets of Langerhans
of pancreas.Its action is initiated by binding to a glycoprotein receptor on the surface of the cells.This
receptor has a beta subunit which is an insulin-stimulated ,tyrosine-specific protein kinase.Stimulation
of this signal results in insulin’s action glucose,lipid and protein metabolism . Insulin lowers the blood
glucose level by promoting utilization and storage

Glycogen synthase enzyme is activated, and so insulin favors glucose storage as glycogen

Insulin favors synthesis of fatty acid from glucose and so glucose utilization is increased

Gluconeogenesis is inhibited by insulin by repressing the key enzymes, pyruvate carboxylase (PC)
phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6- phosphatase

Gluconeogenesis is inhibited by insulin by repressing the key enzymes, pyruvate carboxylase (PC)
phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6- phosphatase (Chapter 9).

Glycolysis is stimulated by insulin. The activity and amount of key glycolytic enzymes (glucokinase,
phosphofructokinase and pyruvate kinase) are increased.

. Insulin depresses HMG CoA synthase and so ketogenesis is decreased

. Insulin increases the activity of acetyl CoA carboxylase and provides glycerol for esterification of fatty
acids to TAG

Hyperglycemic Hormornes
1)Glucagon

Glucagon release is stimulated by low blood sugars.Its secrete d by the alpha cells of pancreatic islets of
Langerhans .Glucagon binds to high affinity hepatic glucagon receptors and its binding leads to the
activation of adenylate cyclase.Adenylate cyclase converts ATP to cAMP(second messanger).CcAMP
activates cAMP dependent protein kinase and this results in phosphorylation and activation
phosphorylase a and inhibition of glycogen synthase.plasma glucose is thus elevated by activation of
hepatic glycogenolysis,ketogenesis,lipolysis, and gluconeogenesis.Glucagon also inhibit the process of
glycogen synthesis which lower glucose levels.

Epinephrine is Secreted by adrenal medulla and enhances release of glucose from glycogen and also the
release of fatty acids from adipose tissue.
Glucorcoticoids is Secreted by the adrenal cortex and increases gluconeogenesis

Adrenocorticotropic hormorne enhances release of cortisol which enhance gluconeogenesis and

antagonizes insulin

Growth hormorne suppresses the abilities of insulin to stimulste uptake of glucose to peripheral tissue
and enhance glucose synthesis in the liver

B Role of carbohydrate metabolic pathways in regulation of blood sugar levels.

Glucose is the center of carbohydrate metabolism and is the major dietary sugar.Other sugars are
converted to the intermediates of of glucose metabolism.After a carbohydrate intake there is high
amount of glucose in the blood and this spike stimulates to liver to converts excess glucose to glycogen
for storage mainly in the liver and muscles.The liver also uses the pathway of glycolysis to convert
glucose to pyruvate which provides carbon for the synthesis of fatty acids.Glycerol 3 phosphate
produced from glycolytic intermediate,combines with fatty acid to form triacyglycerols.These
triacyglycerols are packaged in Very Low Density Lipi protein(VLDL) and transported to adipose tissue
where the fatty acids are stored in adipose tissue.The body also stimulate the transportation of excess
glucose to peripheral tissues such as the brain and also in the pentose phosphate pathway to produce
NADPH for reductive biosynthesis.Blood glucose will eventually be brought to normal due to the above
regulatory carbohydrate pathways.After some hours plasma glucose levels becomes and the body will
use some of the reversal carbohydrate pathways to elevate the blood glucose levels .Low glucose levels
in the blood srtimulates gluconeogenesis and glycogenolysis pathways.Through glycogenolysis adipose
triaglycerols are degraded providing fatty acids as an alternative fuel for glucose supply by
gluconeogenesis.amini acids in muscles are also released to serve as gluconeogenic precursors.stored
fats in adipose tissue produce glycerol needed for gluconeogenesis.Through these pathways blood
glucose level is elevated.

C) 1)Relationship between hyperglycemia and hyperlipidemia

CVD is responsible for 80% of total diabetic mortality. Diabetes is associated with an increase in small
LDL particles, high TG and low HDL levels. In the absence of insulin, hormone sensitive lipase is
activated, more free fatty acids are formed, which are catabolised to produce acetyl CoA. These cannot
be readily utilised, as the availability of oxaloacetate is reduced and citric acid cycle is sluggish. So acetyl
CoA pool is increased, and it is channelled to cholesterol synthesis. In diabetes, the atherogenicity of LDL
is increased while atheroprotective effect of HDL is decreased. In diabetes mellitus, the TAG pool in the
cell is high and the LDL particles formed from VLDL are of the small dense variety, that are highly
atherogenic. The glycation and oxidation of LDL will delay their catabolism and promote the uptake by
macrophages, which is a dysregulated process. At the same time, the level of HDL in diabetic patients
and those with metabolic syndrome is low. Glycation of Apo-A1 decreases its ability to stimulate LCAT,
and thereby the esterification and efflux of cholesterol from the cells. The antioxidant effect
(Paroxonase activity) of HDL is also decreased. The alterations in the level and properties of LDL and HDL
together contribute to the increased risk for CAD in diabetes mellitus.

2)How hyperlipidemia leads to hyperglycemia.

3)Role of HMG-CoA reductase lipid metabolism disorders

D)How Diabetic keto acidosis is brought about and its management.